Bill to Block Gene Patents
Nature Reviews: Drug Discovery
March 2007; 178-9

Bill to block gene patents
by Joanna Owens and Charlotte Harrison

The spectre of patenting natural phenomena is brought to the fore again by proposed new gene patent legislation. If enacted, the Genomic Research and Accessibility Act introduced by Republican representatives Becerra and Weldon would prevent the patenting of any and all portions of the human genome. The Bill will not affect patents that have already been granted.
The new legislation proposes that human genetic material, naturally occurring or modified, should not be patentable. Specifically, the Bill H.R.977 makes an amendment to Title 35 of the US Code and would state that: "No patent may be obtained for a nucleotide sequence, or its functions or correlations, or the naturally occurring products it specifies."
After the human genome sequence was published in 2001, there was a rush of patent applications claiming the identification of genes with only putative evidence of their function. Now, the US Patent and Trademark Office (PTO) has tightened its stance on this, but it is still possible to patent a gene outside its biological context. This means that if you purify, clone, synthesize or alter nucleic acid from its naturally occurring state then you can obtain a patent on that gene in its altered, unnatural form. However, under this proposed new legislation it is unclear whether this will still be possible. The implications for the drug industry if this Bill is enacted will be profound.
In a press statement outlining the Bill, Becerra and Weldon point out that 20% of the human genome has already been patented. They aim to ensure it stops there, saying that the practice of gene patenting violates the spirit of the Human Genome Project and hinders the discovery of medical breakthroughs. They claim that the new Bill will not stifle invention, but that: "Incredible manifestations of intellectual property will result: medicines, machines, processes ... all worthy of a patent." Opponents of the Bill say that the return on investment required for companies to turn genomic information into new drugs must be recognized.




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March 15th, 2007 | Category: Editorials | Published By: nihar
Michael J. Fox, Mary Tyler Moore, Ronald Reagan—we all know them as famous American figures. Fox took us back to the future, Moore was that 70’s sitcom actress, and Reagan, President sure, but also an all-American B movie actor. As celebrities, both their fame and their fights have been publicized; the actors battle with Parkinson’s and Alzheimer’s disease, the actress- diabetes. They suffer diseases we don’t know how to cure, but through various charities they’ve tried to fix that.

Now add to those efforts Marry Jane Gentry, an average wife with a love for speed boat racing and swimming. But now she’s in a race for her life, because amyotrophic lateral sclerosis, or Lou Gehrig’s disease, has slowed her body down. In perspective, Stephen Hawking’s experience with this paralyzing disease is fortunately slow. And while Mrs. Gentry is some anonymous woman few of us could relate with, her average struggle parallels what the famous and the unfamiliar people of this world experience when they suffer a disease without a cure.

Yet with the billions of dollars from donations and private corporations going into drug development, our rate of innovation has been slowing down. And to make things stranger, the cure for some diseases, such as ALS, were discovered years ago. In fact a decade earlier, neurologist Dr. James Bennett discovered the molecule pramipexole just idling on a laboratory shelf. Dr. Bennet—shocked that 5,000 people are diagnosed with ALS yearly—spent 3 years trying to convince the laboratory to develop this cure, racing against the little time Mrs. Gentry had. And when Dr. Bennett finally filed his own patent on the compound’s use, the company laughed it off as an expensive waste of time and let this lone doctor wade through the regulatory thicket of patents on his own.

But this murky world of biological patents and copy writes should be helping us. They provide pharmaceutical companies with incentives. Anticipating huge profits from the monopolies these drug patents provide, biomedical companies throw money at drug development to be the first on the market with a cure. For 20 years, they get to sell their product as cheaply or as expensively as they want. But they don’t reap limitless profits. Once the 20 years are up, the formula is fair game for any company to copy; then competition between different biomedical companies trying to sell the same cure typically drives prices down so more people can afford the product. Take, for example, the generic ibuprofen that’s replaced the monopoly Advil once held. The larger companies like Advil are then expected to repeat the 20-year monopoly cycle by researching new cures for unsolved problems like AIDs and cancer, but last year of the 80 Food and Drug Administration approved drugs, only a quarter were actually new. While new medicine should be advancing with new technology, instead it’s been slowing down.

Pharmaceutical companies are telling us that the 20-year rule is part of the problem. Since brand name drugs typically lose 80% of their sales when generic drugs hit the market, the big company’s reaction is only natural. Sure the companies have 20 years without competition, but it can take 8 or more years just to get the FDA’s approval before they can actually start selling their product. Dr. Bennett filed his patent in 2000, and still waits for approval on distributing pramipexole while other drugs gain approval much easier. In their effort to make up for this inequality, large companies resort to redesigning their existing formulas, tweaking them in the slightest ways just to call it a new drug to win new patents and extra monopoly time. For them its extra money with little new research. Large companies also spend millions coercing the small generic-brand companies to hold off on selling the generic drugs that drive prices and sales down. They may even patent by-products produced in the drug’s creation to stop others from producing it as well—Dr. Bennett had to cite pramipexole’s use, not its actual formula, when he wanted to develop it. Still others spend huge amounts fighting in court over how soon a patent should expire—the average litigation costs over the U.S. patent system is $4million each, though disputes over medical inventions specifically are even costlier. And if all else fails, they pump money into advertisements to directly compete with each other and make the most of their product. Thanks to such ads, we all know that toenail fungus is caused by little yellow monsters that Lamisil pills stomp out. The FDA had to shut down the Lamisil ads for overexagerating, and wasteful advertisements lead to wasted money. According to Forbes staff writer Scott Woolley, the pharmaceutical company Pfizer had spent $7.4 billion dollars researching new cures, while it spent $17 billion dollars on marketing and administration. Just removing the 100,000 strong army of pill-pushing salesmen would save the industry $12 billion, money that could be well spent in researching unsolved diseases.

Yet while clinging to old patents is bad, hoarding new ones is even worse. Other companies have been called patent trolls, filling as many patents as they can merely to collect royalties from whoever may develop the product in the future. But when corporations claim the rights to a life-changing product without any intention to develop it, a potential cure is lost. Dr. Raj Bawa says that, “Patent thickets are considered to discourage and stifle innovation. Claims in such patent thickets have been characterized as often broad, overlapping and conflicting – a scenario ripe for massive patent litigation battles in the future.” And it’s not just the large companies filing frivolous patents and claiming exclusive rights to broad areas of science. Tiny Ariad Pharmaceuticals, for one, filed a patent on a human chemical pathway that dozens of drugs target. Ariad then sought monetary compensation from the other companies that spent time and energy producing said drugs without any idea they were targeting a patented part of the human body. Their lawsuit has been compared to patenting gravity, then demanding all hydroelectric plants that rely on gravity to pay them, yet courts have supported this broad patent and others before it. In another case of extensive patent rights, groups have patented stem-cell research , forcing others to move out of the US into Asia where the patents don’t hold. This is unfortunate because it’s drained talent out of the US and postponed the huge potential stem cells have of curing just about anything, just because patents have discouraged it.

As a result, even as we discover new branches of medicine in stem cell research and nanotechnology, American innovation just isn’t keeping pace. Jack Shapiro, a health care marketing consultant has found that the number of New Drug Approvals has steadily declined since ‘83, and it’s not just because we’ve reached some impassable plateau of innovation. The opportunities are out there, but we’re stuck in a thicket of patents.

If we’re ever going to get out, we have to make medical research and development more efficient. We must have Congress edit its 20 year patent rule as follows:

· First, the Patent and Trade Organization must tighten its requirements on how broad a patent one can file, and review if they are being used or hoarded .

· Second, and most importantly, instead of granting the exclusive ability to sell a medical product 20 years after the patent is filed, they could grant a 15-year monopoly period after the product is FDA approved for selling.

This way, all companies would get an equal amount of time to sell their drug without competition, regardless of the variable amount of time they take developing it. And with the rules tightened, courts won’t let businesses hoard broad patents, and large companies won’t have an excuse to sue, settle, or file frivolous patents to keep generic drugs out, saving consumers money through more cheaply produced drugs. Every medical innovator will have an equal amount of time to make their fair share of money. Everyone would be on equal ground. And with fewer frivolous patents being filed, the backlog that makes companies wait years for patent decisions would be reduced.

Because for now, the years of delay are only hurting us. By the time Dr. James Bennet was approved for testing his drug, Marry Jane Gentry had died, along with most of the ALS victims that Dr. Bennett knew personally. And now, years later, the number of new drugs approved has gone down, not up. Until the system is changed, this trend will only continue. Pharmaceutical companies will pour millions of dollars into manipulating the patent system, while stealing from the R&D that could save millions of lives.

If a company can patent a gene line, then smaller drug companies would have to pay the larger drug company for the rights to do research on the gene line for other diseases that might be cured, but the larger company will not put the money into research for.

The patients would be the ultimate people to suffer.

Vicky

Thelma, I'm confused about the Dr. Bennett and pramipexole mentioned in your post. If i'm not mistaken, pramipexole is our old friend Mirapex. Is it useful in treating ALS?

R(+) Pramipexole

Treatment classes: Small Molecule

Synonyms: Pramipexole=S(-) PPX,Mirapex®, Mirapexin® Sifrol®; R(+)PPX= SND919CL2x
Development Status: Approved US, Phase II

Pipeline Status: Closeout

Disease Indications: R(+)PPX is in Ph II for ALS. The (-) stereoisomer of pramipexole is FDA approved for Antiparkinsonian, dopaminergic
Manufacturers: Jim Bennett
Targets: mitochondrial permeability transition pore

Rationale for ALS: The dopamine agoinst Mirapex (the (-) stereoisomer of pramipexole) is also an inhibitor of the mitochondrial permeability transition pore. The permeability transition pore in the inner mitochondrial membrane is known to play a role in the apoptotic signaling cascade and blocking the permeability transition pore may have a neuroprotective effect. In fact, Mirapex has been shown to protect neuronal cells from apoptosis. However, due to Mirapex’s high affinity for the D2 dopamine receptor, its dosage for effective neuroprotection would have too many side effects. James Bennett (of Univ. Virginia) noticed the (+) stereoisomer of pramipexole (R(+)PPX) still has the same neuroprotective effects but has 100-fold less affinity for dopamine receptors, and could therefore be used at a much higher dosage, and proposed its use as a therapy for ALS. It has also been shown to reduce oxidative stress in ALS patients (4) and SOD1G93A mice (5).


Title: Use of pramipexole to treat amyotrophic lateral sclerosis
Document Type and Number: United States Patent 7157480
Link to this Page: http://www.freepatentsonline.com/7157480.html
Abstract: The present invention is directed to compositions comprising pramipexole and the use of such compositions to treat neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). As shown in FIG. 6B the mean +/- SEM serum 2,3-DHBA levels for the 12 ALS participants decreased significantly after pramipexole treatment.


July 19, 2006
Variant of Parkinson’s Drug Tested In ALS
Investigators at the University of Virginia in Charlottesville are testing a compound known as R(+) pramipexole in people with amyotrophic lateral sclerosis (ALS) to see whether it alters their decline in function or changes biochemical markers of the cell-damaging process known as oxidative stress.
James Bennett, a professor of neurology at the University of Virginia School of Medicine, became interested in testing R(+) pramipexole in ALS a few years ago, after S(-) pramipexole, whose structure is a mirror image of the R form, was found effective in Parkinson’s disease.
S(-) pramipexole was developed into the drug Mirapex, which mimics the brain chemical dopamine and acts as an antioxidant, combatting oxidative stress. It enters the nervous system and the mitochondria, the sites of energy generation inside cells.
Bennett, a physician who has a doctoral degree in pharmacology, recently found that 15 ALS patients tolerated 30 milligrams a day of R(+) pramipexole, which does everything the S(-) form does except mimic dopamine, which isn’t a goal in ALS treatment.
Thirty milligrams is about five times the tolerable dose of the S form, says Bennett, who’s now testing one ALS patient at a time to see how high he can boost the dose of the R form.
The investigators aren’t seeking new trial participants at this time, but they may be in the future.
“So far the results are encouraging for slowing disease progression,” Bennett says, “but there aren’t enough data yet to draw any firm conclusions.”
For more information, see R(+) Pramipexole in Early ALS.

Thanks, Thelma. This is extremely interesting.

I had read last year that opening of the mitochondrial permeability transition pore may be involved in apoptosis of neurons leading to PD, but there was no mention of pramipexole or that the R(+) isomer has selective pore-closing activity.

It is especially interesting in view of the previous claims of neuroprotection for the dopamine agonist form, the R(-) isomer (Mirapex). Maybe a mixture of the two forms would have even greater neuroprotective effect, while maintaining the dopamine agonist activity!

(p.s. I had to edit this posting to get the +/- signs of the isomers right!)