Topic #6: DNA and Organism Patenting(Bioethics final)

http://www.genomicslawreport.com/wp-content/ uploads/2010/03/Myriad-SJ-Opinion.pdf

"The information encoded in DNA is not information about its own molecular structure incidental to its biological function, as is the case with adrenaline or other chemicals found in the body...this informational quality (of DNA) is unique among the chemical compounds found in our bodies, and it would be erroneous to view DNA as 'no different' than other chemicals previously the subject of patents....DNA, in particular the ordering of its nucleotides, therefore serves as the physical embodiment of laws of nature - those that define the construction of the human body...the preservation of this defining characteristic of DNA in its native and isolated forms mandates the conclusion that the challenged composition claims are to unpatentable products of nature."

Useful

It isn't enough just to find a new gene or protein. The inventory must specify what the uses are; for example, whether the gene or protein is useful as a drug for disease X or as a target for disease Y or as a diagnostic marker for disease Z.

the fish grow eight times as fast as normal salmon.

The patent specification shows that......?

The Patent and Trademark Office(USPTO)

The patentability of inventions under US law is determined by what?

grow faster, have increased nutritional value and lower fat content.

The processes described result in pigs that ........?

Dolly the sheep

The research team that cloned _____________________ , owns a patent that gives them rights to all cloned animals using "their" method(2001).

20 years

The term of a new patent is how many years from the date on which the application for the patent was filed.

BRCA1 and BRCA2

The two genes patented by Myriad Genetics, _______ and ________, code for two different proteins that help repair DNA damaged. IF either of these genes has a mutation, which has been inherited or from old age, then the remaining cell DNA is not repaired. The cell can then develop additional genetic mutations that dramatically increase a woman's chance of developing breast and ovarian cancer.

The University of California, Berkeley, and Massachusetts Institute of Technology/Broad Institute

There was a patent battle between who?

California will get the patent for using the system called CRISPR-Cas9 in any living cell, from bacteria to blue whales. MIT/Broad will get the patent in eukaryotic cells, which is to say, plants and animals.

What did the U.S. Patent Trial and Appeal Board conclude for this case?

You can't patent nature and you can't patent a fundamental idea of science

What did the judge basically state?

They have a patent on green tennis balls; we have a patent for all tennis balls.

What is a good analogy to describe this very confusing outcome?

Identifying carriers of an inherited BRCA gene mutation

What is an important step in helping women avoid breast and ovarian cancers?

disclosure of innovations into the public domain

What is it that Patents facilitate and encourage for the common good?

Human Genome Project-Write(HGP-write)

A group of Researchers are currently proposing to synthesize entire genomes from scratch, including those of humans. What's it called?

1. "Novel"(i.e. not known or used before the filing) 2. "Non-obvious"(a patent is obvious, and therefore invalid, if an improvement that can be easily made by someone of "ordinary skill" trained in the relevant area). 3. "Useful" in a practical sense(the inventor must identify some useful purpose for it). 4. The invention also must be described in sufficient detail to enable one skilled in the field to use it for the stated purpose (sometimes called the "enablement" criterion).

A patent application is judged on several criteria; the invention must be:

patent

A _______ for an invention is the grant of a property right to the inventor, by the federal government. Grants the right to exclude others from making, using, and selling the invention for a limited time.

Biological patent

A __________ ________ is a "patent on an invention in the field of biology that by law allows the patent holder to exclude others from making, using, selling, or importing the protected invention for a limited period of time."

It has to have some change with respect to what is found in nature, and the change has to provide some markedly different property.

A product that is going to be patented has to what?

Metamorphix

Bought CELERA in 2002 and thus gains access to proprietary genome data on cattle, pigs, and chickens. they then enter exclusive license contracts with major genetics companies.

1 in 10

Breast cancer affects about ___ ___ _____ women.

Allow for the ability to chemically fabricate the complete set of human chromosomes and could theoretically allow the creation of babies without biological parents.

As a result of this Project, the ability to fabricate huge stretches of DNA could: What are the Cons?

Allow for numerous scientific and medical advances. It might be possible to make organisms resistant to all viruses, for instance, or make pig organs suitable for transplant into people.

As a result of this Project, the ability to fabricate huge stretches of DNA could: What are the Pros?

68,000; 2,600; 109,000

As of February, 2014 there were approximately ___________DNA-based patents granted by the United States Patent and Trademark Office(USPTO) related to genes, fragments of genes, genetic processes, and bits of DNA as small as a single letter change in the genetic code. About ________ patents are for isolated DNA. From 2001 to February, 2014, there were approximately __________ DNA patent applications submitted to the USPTO.

rabbits

In 2005, a patent was granted for _________ whose eyes are intentionally damaged to serve as a model for "dry eye" conditions in humans. "This invention provides experimental animals suffering corneal epithelial damages and methods of using the same to assay a variety of compounds for evaluating the therapeutic effect on the disease, and medicine selected using the method..."

Newsham Genetics(now called Choice Genetics)

In 2007, Monsanto sold their swine breeding business to ____________ ____________.

Synthia

In 2007, scientists at the J. Craig Venter Institute applied for a U.S. patent on __________. The patent involves a minimal set of protein-coding genes which provides the information required for replication of a free-living organism in a rich bacterial culture medium.

improperly granted

In 2010, the federal judge in the lawsuit ruled that the challenged claims to the isolated gene sequences had been __________ ___________ because they claimed unpatentable subject matter.

human genome

Based on current laws, there is a very good chance that this type of project would make it possible to patent a ___________________ for the first time. The Supreme Court ruling in the Myriad Genetics case from 2013, makes this possible.

1. Researchers are rewarded for their discoveries and can use money gained from patenting for further research and development. 2. Wasteful duplication of effort is prevented. • Research is forced into new, unexplored areas. 3. Secrecy is reduced and all researchers are ensured access to the new invention. • Patents facilitate and encourage disclosure of innovations into the public domain for the common good. 4.The cost of commercialization is far more than the initial conception cost. • Unless there is some way to prevent copies from competing at the marginal cost of production, companies will not make that productization investment. 5. Causes competitors to design around (or to "invent around") each other's patents. • This may promote healthy competition among manufacturers, resulting in gradual improvements of the technology base.

Benefits of Patenting DNA include:

1. New compositions of matter related to: newly discovered isolated nucleic acids, proteins, pharmaceutical inventions based on these nucleic acids, or proteins or cell lines transformed by nucleic acids. 2. Methods of making the above products through, for example, transformation technology or cell culture technology. 3. Methods of treating patients with a given disease through the use of a particular gene or protein.(Even if someone has a patent on a gene or protein, a second inventor can obtain a patent on a new use of that gene or protein, if the second inventor discovers a new use for the substance. Such methods of treatment can also include delivery mechanisms.) 4. Methods of detecting or monitoring disease states such as through detection assays.

Biological inventions generally fall into one of the following classes:

MIT was awarded the patent in 2014, and in April 2015, California asked the USPTO to determine which team was the first to invent the technique and earlier last year, awarded California's request.

California originally filed for a patent in March, 2012 and MIT filed for a patent in October, 2012 under a slightly different manner. What came of this?

royalties

Companies holding patents on new plant/animal forms have the authority to require users to pay _____________. These would be paid on the sales of patented plants/animals and on generations of their offspring. EX: Farmers would have to pay patent holders a fee for adult animals and for generations of calves, colts, lambs, chicks, and piglets produced through the life of the patene.

1. Patents of partial and uncharacterized DNA fragments will reward those who make routine discoveries but penalized those who determine biological function or application(inappropriate reward given to the easiest step in the process). 2. Patent stacking(allowing a single genomic sequence to be patented in several ways such as a fragment and a gene) and monopolies may discourage product development because of high royalty costs owed to all patent owners of that sequence; these are costs that will likely be passed on to the consumer. 3. Because patent applications remain secret until granted, companies may work on developing a product only to find that new patents have been granted along the way, with unexpected licensing costs and possible infringement penalties. 4. Pharmaceutical patents prevent generic alternatives from entering the market until the patents expire, and thus maintain high prices for medication. 5.Patent holders are being allowed to patent a part of nature, a basic constituent of life; this allows one organism to own all or part of another organism. 6. Now that all approx. 20,000 human genes have been mapped and sequenced through the Human Genome Project, they are in the public domain, meaning they no longer are considered "new" for the purposes of patents. Thus, patents on human genes must be novel and specify a new use, such as a diagnostic test.

Controversies of Patenting DNA include:

CELERA

Craig Venter's company analyses the human genome and the genomes of cattle, pigs, and chickens

The appeals court reversed their original decision, by saying that DNA isolated from the body could be patented because it was markedly different in chemical structure from the DNA inside the body.

In 2011, the federal appeals court announced that Myriad is entitled to patents on the BRCA1 and BRCA2 genes. How?

it is a simple application of a law of nature

In 2012, the Supreme Court ordered an appeals court to reconsider its decision to uphold patents held by Myriad Genetics. What was the notion based on?

synthetic DNA

In 2013, the Supreme Court came to a final decision that isolated, but otherwise unmodified DNA should not be patent eligible. But, _________ _______, with a sequence different from anything found in nature, are patent eligible.

Color Genomics

In 2015, a company by the name of ________ __________ started offering a $249 saliva test kit for women that checks for variants in 30 genes known to be correlated with a higher risk of breast, ovarian, colon, and pancreatic cancers, including mutations in the BRCA1 and BRCA2 genes.

"raw products of nature"

In general. _____ ________ ___ _______ are not patentable.

It was not whether it was inanimate, but whether it was a product of nature or of human invention.

In 1980, the Supreme Court laid the legal foundation that would establish the United States as the global biotech patent leader. The threshold question for patentability of an organism was based on what?

oncomouse

In 1987, a Harvard biologist was granted the first patent for an animal. The __________ was genetically engineered to predispose it, and all its' offspring, to develop cancer, so they can be used for research. The patent extends to any other animal genetically engineered to contain genes that cause cancer(expired in 2005).

University of Missouri

In 2001, a patent was awarded to ________________________ for turning unfertilized eggs into embryos, and the production of cloned mammals using that technique.

If someone makes a kind of mouse that never existed before, then that kind of mouse might be patented.

For example, one cannot patent a "normal" mouse, because mice have been around for a long time. BUT....

cDNA(can be reversed with regular Transcription)

Genomic DNA + Transcription --> Pre-mRNA + RNA splicing --> mature mRNA + Reverse Transcription---> ?

Protein

Genomic DNA + Transcription --> Pre-mRNA + RNA splicing --> mature mRNA + Translation --> ?

The U.S. Plant Patent Act of 1930

Granted property rights for privately developed plant varieties for asexually reproducing plants.

Greenpeace; Monsanto

Has filed an objection to the patent on ethical grounds. A second objection was made by ____________, the company claims similar processes to be its invention.

the breeding of pigs

In 2005, Monsanto, had filed two patents for processes which controlled _________________________, from conception to slaughter.

In every one of these cases, the jury or court decided in Monsanto's favor

How many cases has Monsanto lost?

either by genetic diagnosis and bred normally, or by having more milk genes additionally incorporated into their genome.

How were these patented cows produced?

AquaBounty

If such super-salmon escape into the environment there is a substantial risk they will displace natural salmon of the same species. Similar to that of _____________.

Novel and Non-obvious

In patenting a gene or a protein, the requirement for novelty and non-obviousness usually means that the inventor must have modified the new gene or protein in some manner.

1. Identify novel genetic sequences. 2. Specify the sequence's product. 3. Specify how the product functions in nature(its substantial use). 4. Enable one skilled in the field to use the sequence for its stated purpose.

In terms of genetics, inventors must:

Belgium and New Zealand

Inventors of the manipulated dairy cows were from where? -They claimed the processes for breeding cows gave more milk or milk with altered constituents.

products of nature

Isolated but otherwise unmodified DNA/genes are considered __________ ___ ______ and are therefore not patent eligible subject matter.

20%(3,000-5,000 actual genes)

It is estimated that about ______ of our genes have been patented (3,000 to 5,000 actual genes).

Georgetown University

Kept a database of DNA patents, but funding for the project ended in late, 2015. As of February, 2014 there were approximately 68,000 DNA-based patents granted by the United States Patent and Trademark Office(USPTO) related to genes, fragments of genes, genetic processes, and bits of DNA as small as a single letter change in the genetic code. About 2,600 patents are for isolated DNA. From 2001 to February, 2014, there were approximately 109,000 DNA patent applications submitted to the USPTO.

Monsanto:pigs, Cargill:cattle, Hubbard(Grimaud Group):poultry, and Willmar:poultry

List 4 major genetics companies Metamorphix enters exclusive license contracts with:

1. Should DNA be patentable? 2. Who owns the rights to your DNA? 3. Should animals and plants be patentable?

List a few Debate topics

it wants the ability to track which animals come from its system.

Monsanto claims that it is not trying to patent pigs; What is it that they are claiming?

When farmers purchase a patented seed variety, they sign an agreement that they will plant only the seed they purchase from us and they will not save and replant seeds produced by the plants they grow.

Monsanto does become aware, through our own actions or through third-parties, of individuals who are suspected of violating our patents and agreements. Has sued many farmers for patent infringement. What is done to ensure that the farmers are aware of the patent?

90%

Monsanto owns _________ of all transgenic crops in the world.

150; 10

Monsanto- "Where we do find violations, we are able to settle most of the cases without ever going to trial." Approx. ________ lawsuits have been filed since 1997 in the U.S. To date, how many of these cases have gone through full trial?

disease processes

Most gene patents involve genes that appear to be important in _______ _________.

BRCA1 and BRCA2; that the patents prevent some people from accessing medical screening for BRCA1 and BRCA2

Myriad Genetics- Lawsuit: In 2009, a lawsuit was filed against Myriad Genetics (and the University of Utah Research Foundation), for the patents to the_____ and _____ genes. The lawsuit asserted what?

In other words, even though the company had figured out hundreds of the key genes involved with a higher risk of breast and ovarian cancer, they had not invented anything. Rather they had simply found something already existing in nature

Myriad Genetics- Lawsuit: Myriad applied for a US patent in 1994 on the BRCA1 gene sequence and later for patent protection on both BRCA1 and BRCA2 in Europe and other nations. In May 2004, the European Patent office revoked Myriad's patents; The EPO decided that while Myriad had figured out the composition of key genetic sequences, it had not done enough to meet the "inventiveness" standard required of a patent. Explain reasoning for the patent revokal.

$4,000(currently approx. $3,000)

Myriad charged approx. ___________ for its diagnostic cancer test, a price that prevents some women from seeking this preventive measure.

a gene or protein that has been isolated from the body and is useful in that form as a drug, screening assay or other application

One cannot patent a naturally occurring gene or protein as it exists in the body, but one can patent what?

human insulin; Genentech; human protein

One of the earliest gene patents was for the cloned gene for ______ _______; _________ cloned the DNA in 1978 and the _______ _______ was first marketed in 1982.

23andMe

Other companies, including __________, also have kits that analyze for BRCA1 and BRCA2 variants.

660

Over ______ animals had been patented, including turkeys, nematodes, mice, and rabbits. Hundreds of other patents are currently awaiting approval, including patents on pigs, cows, fish, sheep, and monkeys.

DuPont

Owned the oncomouse patent. The corporation that financed the research.

the "first to invent" principle

Patent priority is based on __________________: Whoever made the invention first(and can prove it) is awarded property rights for the 20-year period. Inventors have a one-year grace period to file after they publish.

17 years

Patent rights were extended to "distinct and new" asexually reproduced plants for a period of how long?

$100 million

The initiative could take 10 years and a minimum of __________ just to get started.

the perception that our genes are owned by somebody else; that these owners can do whatever they want with these genes.

Several bills have been introduced in Congress over the past decade that would ban the patenting of DNA. • These bills are based on what?

the patent was rescinded

Several organizations question this idea of whether rabbits and other animals whose eyes have been purposely damaged can be patented. As a result, it was filed for re-examination of the patent. In 2008, what happened?

lower prices for breast cancer diagnostic kits and has allowed women to get independent second opinions

Since the Supreme Courts' decision, several companies have gotten into the market of testing and analyzing for the BRCA genes. What has this led to?

GM, genetic alterations that use chemicals or radiation, and fusing embryos of different special species

Some of these plant and animal alterations include:

Seabright

The Canadian company, _________, was granted a patent for salmon and other fish which have been manipulated with growth hormone genes(2001).

Autodesk Research

The Genome Project-Write is backed by the top Researchers in the field and __________ ___________.

engineering plants, animals, and microbes

The Project founders say they do not want to create designer babies but maintain that focusing on a grand challenge like synthesizing an entire human genome would be the best way to galvanize advances in DNA synthesis that could be used for more practical purposes, such as ........?

XY Inc.

The U.S. company _________ was granted a patent for a method for selecting sperm by sex for the artificial insemination of mammals, including people(2005).

non-naturally occurring nonhuman multicellular living organisms, including animals

The United States Patent and Trademark Office, allows companies to patent higher forms of life, including plants and animals, that have been altered through a number of methods. So what is said to be patentable subject matter in this case?

BioTransplant

The University of Missouri has licensed the patent to ___________, a Massachusetts biotechnology company that is working on creating pigs that can be used as human organ donors. The license covers only the use in pigs.

deep-frozen sperm itself

The ______________________ is also claimed as an invention.

1. All BRCA1 and BRCA2 testing had to be done through them. 2. Also prevented other researchers and doctors from making use of the genetic information for medical applications.

The awarded patent to Myriad Genetics involved the following:

Myriad appealed the decision

The court ultimately ruled that the patents on human genes held by Myriad Genetics are invalid. What happened later that year?

1 in 500

The frequency of BRCA1 and BRCA2 gene mutations is approximately ____ ___ _______.

J. Craig Venter Institute

They claim exclusive ownership of a set of essential genes and a synthetic "free-living organism that can grow and replicate" that is made using those genes.

Mississippi had already existed in the world, but someone decided to map the land and sell those maps to the public. They had not invented Mississippi, but rather found it and mapped it out.

Thus, patents on human genes must be novel and specify a new use, such as a diagnostic test. For Example: Think of Mississippi:

within the US, US territories, and US possessions

US patent grants are effective only where?

a process, a machine, an article of manufacture, and a composition of matter

Under US law, various types of inventions can be patented:

A process

Under US law, various types of inventions can be patented: for example, a process of making a chemical by combining chemical X with chemical Y, or a method of treating aa cancer patient by administering a specific drug.

A machine

Under US law, various types of inventions can be patented: for example, a flat-screen, high-definition television set or an X-ray machine.

A composition of matter

Under US law, various types of inventions can be patented: for example, a new pharmaceutical drug or a new plastic for use in kitchen counters.

An article of manufacture

Under US law, various types of inventions can be patented: for example, a silicon computer chip or a specially molded piece of plastic for an automobile bumper.

1. Out of economic necessity, farmers had the right to save, replant, and resell seeds to other farmers willing to buy seeds with desirable characteristics. 2. The genetic composition of seeds, rather than the seed itself, was considered part of a common heritage and widely shared among farmers. 3. Seeds were not seen as a commodity; rather, the right to use and reproduce seeds was inherent in the first purchase of the seed.

Up until the last few decades, certain concepts were universally accepted among farmers:

Microbesoft

Venter's company is positioning itself to become the _______________ of synthetic biology.

commercial race to synthesize and privatize synthetic life forms

We think these monopoly claims signal the start of a high-stakes what?

it does not specifically exclude human from its definition of mammals; it specifically mentions the use of human eggs

What about this patent is unlike other patents on animal cloning?

to develop technologies to more efficiently and more cheaply write DNA

What is the underlying goal of the proposed project HGP-write?

Cattle, pigs, and horses

What mammals in particular are singled out in this patent?

2007

When was the first European patent on genetically manipulated dairy cows granted?

synthetic DNA(gene fragments and whole genes)

While unmodified DNA/genes are not patent eligible, _________ ______ Can be patented, in addition to proteins, cells, organisms, and associated medical and research tests and tools

the patents filed would lead Monsanto to owning not just the breeding process, but also the pigs which are bred from this method

Why are the farmers worried about Monsanto's pig patent?

A DNA patent

gives its owner the exclusive right to control its' use for research, diagnosis, or treatment.

Patent

is basically a limited property right that the government offers to inventors in exchange for their agreement to share the details of their inventions with the public. Like any other property right, it may be sold, licensed, mortgaged, assigned or transferred, given away or simply abandoned.

Monsanto(St. Louis, MO)

is the world leader in genetically modified plant patents. Patents many of the seed varieties we develop. Patents are necessary to ensure that we are paid for our products, and for all the investments we put into developing these products. Currently invest several million dollars per day to develop and bring new products to market.

genetic diagnosis

marker assisted breeding

Crop Protection

the collection of tools, products, and practices farmers use to defend their crops against weeds, insects, and disease. Farmers around the world make multiple decisions each day regarding how best to protect their crops. Weeds steal water, sunlight, and nutrients from crops. Insects and disease can also have a devastating impact on food production. Fortunately, advances in modern agriculture have provided them with a variety of solutions for the task.(on Monsanto's web page)

Myriad Genetics(Salt Lake City, Utah)

was granted a patent for two genes involved in breast and ovarian cancers in 1995.

CRISPR-Cas9

works as a type of molecular scissors that can selectively cut parts of DNA, and replace it with new DNA.