Pharmaceuticals Sports & the Maria Sharapova Case: The Latvian Inventor of Meldonium Defends the Safety of the Allegedly Performance-Enhancing Miracle Drug aka Mildronāts, Mildronate, Quaterine, MET-88, THP (not Available in the USA or Germany) - See more at: http://lawpundit.blogspot.com/#sthash.zq1du45E.dpuf

The Latvian Inventor of meldonium (also known as mildronāts, Mildronate, Quaterine, MET-88, or THP) has defended the safety of the allegedly performance-enhancing drug that has brought Russian tennis star Maria Sharapova into an alleged doping crossfire, very likely unjustly, because, as Ivars Kalvins of Latvia's Institute of Organic Synthesis has stated, there is no clinical evidence that taking meldonium improves athletic performance per se.

Meldonium is a curious case because the substance was only put on the athletically prohibited list of drugs this year, in 2016, whereas the medication was already invented in the 1980s and used for livestock. Clinical trials on humans were conducted in 2005 for its use as a heart medication. As written by Eric Niiler at Wired (yes, two i's) in The Quirky History of Meldonium, From a Latvian Lab to Maria Sharapova:

"The [Latvian Institute of Organic Synthesis] demonstrated meldonium’s ability to treat effects of heart failure, myocardial infarction, arrhythmia, atherosclerosis, and diabetes, as well as how it boosts the sexual prowess of boars."

As Niiler writes further, the World Anti-Doping Authority (WADA) has stated off the record that meldonium was put on the prohibited list because it is allegedly "an energy efficiency catalyst that increases oxygen uptake, enhancing stamina and endurance." WADA is being careful in its statements on the record because they are in hot water legally, having no evidence that meldonium improves athletic performance, nor is there any evidence that meldonium is harmful to athletes -- quite the contrary, all available evidence indicates that meldonium, as a CYTOPROTECTIVE SUBSTANCE -- is beneficial for health -- perhaps for everyone!

In his Wired article, The Original Users of Meldonium, Sharapova’s Banned Drug? Soviet Super-Soldiers, Niiler points out that the drug has been used for many years, and quotes Kalvins, a European Patent Office finalist for the European Inventor Award in 2015 for his work on meldonium, as follows:

"Kalvins says the [Sharapova] ban is literally a crime. “It’s a violation of human rights,” he says. “The sportsmen should be able to protect their health. We are living in an era of evidence-based medicine, so there are not any other new data supporting the ban.” He calls the prohibition “sudden” and “a surprise.”" [emphasis added]

In fact, meldonium is a registered drug in Latvia, Russia and East European countries and has been prescribed for heart patients for years because -- if taken as indicated under the supervision of a physician -- it has proven beneficial not only for heart indications but for health in general, as detailed at the end of this posting.

The slow-moving U.S. Food and Drug Administration has not approved it yet.  See Flash - Inventor defends safety, questions ban on Sharapova drug - France 24. It is also not yet approved in Germany, in spite of clinical trials that were published already in 2010 in Seminars in Cardiovascular Medicine, 2010; 16:3. That failing in the USA and Germany, of course, may have much more to do with big money and pharmaceutical politics rather than the honest attempt to provide the best medicine to citizens via new substances, especially if the patents to those substances are owned by foreign firms.

At any rate, as a legal matter, it simply can not be the case that substances that are beneficial to the heart and the circulatory system are put on lists of substance prohibitions for athletes -- just because athletes use them beneficially. That is really quite absurd.

Many athletes surely stress their hearts more than your average person and thus taking vitamins or other medications to protect their hearts and health surely is not "doping" per se at all. We should in fact rather encourage athletes to take supplements which are beneficial to them and their organs and which make them stronger, presuming the drugs are not harmful.

Better heart health could of course result in better athletic performance in any sport, and especially so in tennis, which puts a lot of stress on the circulatory system, but to ban substances that improve an athlete's overall health can not be the purpose of prohibitory athletic doping laws. That simply goes too far in terms of sports officials interfering with people's free choice and, paradoxically, likely HARMING their health through prohibition.

There must be a line drawn between permissible supplements that improve the health of athletes as opposed to drugs such as steroids that are used primarily to enhance muscle size and thus to gain an unfair athletic advantage in strength sports. Moreover, steroid abuse has been shown to be dangerous to the health of athletes. But what about other "supplements"?

We ourselves find that eating honey and peanut butter sandwiches prior to tennis matches or other athletic endeavors appears to be beneficial for winning or losing -- for us. Calories to burn as it were. Dehydration can also be a severe problem for athletic performance and we swear by Coca-Cola (R) in such cases. Who is anyone to prohibit us from doing that?! In other words, there must be sensible limits to drug doping law prohibitions.

The world is constantly moving forward and new discoveries are being made every day that have the potential to improve human health. There is no way that all such new discoveries can be prohibited for athletes. That would be unsupportable discrimination against athletes. Indeed, the athletes may be serving in the course of their competitions as models for the rest of us, who down the road may in fact find ourselves taking the same substances to lead a better life. Meldonium certainly looks like one of those substances.

Be that all as it may, meldonium is manufactured only in Riga, Latvia by the pharmaceutical firm Grindeks (Grindex), and prescriptions of the drug have shot up considerably since the Sharapova case became public.

As written at France24 about the clever Mayor of Riga and meldonium, and we would not be surprised if tourist traffic to Riga increased as a result:

"Meanwhile, the mayor of Riga, Nils Usakovs has turned the controversy over the drug into a cheeky promotional initiative.

On his Twitter and Instagram accounts, he has mocked up a holiday-style poster, decorated with swimsuit-clad women, with the slogan: 'Welcome to Riga, meldonium home city!'"

Here is what the pharmaceutical company Grindeks (Grindex) has written recently at its website about meldonium in Meldonium should not be included in the Prohibited list [note that the company is not doing this to INCREASE sales, rather sales of meldonium have increased because of the prohibition]:

"Despite «Grindeks»’s submitted arguments, evidence and justifications, the World Anti-Doping Agency (WADA) included meldonium in the Prohibited list. In accordance with the results of the extended research, «Grindeks» has a firm conviction that meldonium should not be included in the Prohibited list. It is unclear to «Grindeks» why the WADA included meldonium in the Prohibited list, because it never gave any explanation of this decision. The company will continue to use all the options and will stand up for to the exclusion of meldonium from the WADA’s Prohibited list.

Mildronate® is a registered trademark of the JSC «Grindeks». Its active pharmaceutical ingredient (or active substance) is meldonium which is responsible for the pharmacological and therapeutic effects of Mildronate®. It should be noticed that inclusion of meldonium (Mildronate®) in the Prohibited list doesn’t change the fact that it is a medicine of high quality, safety and efficacy. Until now it has been available to everyone, including athletes, to prevent the negative effects caused by physical and psycho-emotional overload.

Mildronate® is widely used in the clinical practice. During increased physical activity, it restores the oxygen balance of tissue cells as well as activating the metabolic processes that result in lower requirements of oxygen consumption for energy production. Mildronate® is widely recognized by health care professionals and patients, and this may include athletes as well.

Mildronate® is mostly prescribed for patients to treat heart and cardiovascular diseases, including stable angina pectoris, chronic heart failure (NYHA I-III functional class), cardiomyopathy, functional cardiovascular disorders; also when there are acute and chronic ischemic brain blood circulation disorders, reduced working capacity, physical and psycho-emotional overload as well as during the recovery period after cerebrovascular disorders, head injury and encephalitis.

Depending on the patient’s health condition, the treatment course of meldonium preparations may vary from 4 to 6 weeks. The treatment course can be repeated twice or thrice a year. Only physicians can follow and evaluate patient health condition and state whether the patient should use meldonium for a longer period of time or not according to the information provided in the patient leaflet and summary of product characteristics.

Meldonium is a cytoprotective substance, which is used to prevent death of ischemic cells, and not to increase performance of normal cells. The mechanism of action of meldonium is based on limitation of carnitine biosynthesis, which leads to deceleration of fatty acid oxidation and activation of glycolysis. Unlike carnitine, meldonium doesn’t cause increase of muscle mass and physical properties. Meldonium decreases cellular damage from ischemia by reducing accumulation of detergent substances (acylcarnitine and acyl-coenzyme A) in the mitochondria. It means that meldonium reduces the ability of an organism to use fatty acids as its energy source. This is important in the treatment of pathologies associated with heart muscle ischemia (stenocardia, heart failure), because in these cases the heart is not getting enough oxygen and nutrients. Consequently, meldonium is a cytoprotective substance, which is used to prevent death of ischemic cells, and not to increase performance of normal cells. It means that meldonium cannot improve athletic performance, but it can stop tissue damage in the case of ischemia. That is why this therapeutic drug is not a doping agent.

Good safety profile of Mildronate® should be particularly emphasized. This is one of the key factors explaining its wide recognition among the doctors and patients. The Mildronate®’s safety is confirmed by its periodic safety update records and the results of published clinical studies. Based on available data, no adverse reactions related to Mildronate®’s use in athletes have been registered."

Meldonium looks pretty good to us, and WADA has clearly made a mistake in putting a substance on the prohibited list which has not been proven to be harmful nor has it been proven that it confers an unfair advantage in sports.

Moreover, as a personal matter and on behalf of people who might be helped to lead better lives with meldonium, we want to know why the substance is not available in the USA and Germany, where the local pharmaceutical company monopolies are reaping gigantic profits by providing us with what may turn out to be less effective cardiovascular substances than meldonium.

Hat tip to CaryGEE.

Crossposted at LawPundit and SportPundit.

Bowman v. Monsanto Co.: U.S. Supreme Court Limits Doctrine of Patent Exhaustion by Prohibiting Purchasers from Making and Marketing Replicas of Patented Soybeans

As we previously predicted at LawPundit on the basis of the oral arguments to the case, the U.S. Supreme Court decided unanimously in favor of the patent holder in Bowman v. Monsanto Co., holding as follows in an opinion by Justice Kagan:

"Under the doctrine of patent exhaustion, the authorized sale of a patented article gives the purchaser, or any subsequent owner, a right to use or resell that article. Such a sale, however, does not allow the purchaser to make new copies of the patented invention. The question in this case is whether a farmer who buys patented seeds may reproduce them through planting and harvesting without the patent holder’s permission. We hold that he may not."

The Court ALSO stated by way of limitation as follows:

"Our holding today is limited—addressing the situation before us, rather than every one involving a self-replicating product. We recognize that such inventions are becoming ever more prevalent, complex, and diverse. In another case, the article’s self-replication might occur outside the purchaser’s control. Or it might be a necessary but incidental step in using the item for another purpose. Cf. 17 U. S. C. §117(a)(1) (“[I]t is not [a copyright] infringement for the owner of a copy of a computer program to make . . . another copy or adaptation of that computer program provide[d] that such a new copy or adaptation is created as an essential step in the utilization of the computer program”). We need not address here whether or how the doctrine of patent exhaustion would apply in such circumstances. In the case at hand, Bowman planted Monsanto’s patented soybeans solely to make and market replicas of them, thus depriving the company of the reward patent law provides for the sale of each article. Patent exhaustion provides no haven for that conduct.

By so doing, the Supreme Court took the simplest path of decision in this case and applied a clear legal standard to the undenied facts, as the Court should do, without problematical hair-splitting concurrences or dissents. Well done.

Crossposted from LawPundit.

U.S. Supreme Court Likely to Hold in Bowman v. Monsanto that Unauthorized Self-Replicated Copies of Patented Monsanto Seeds are Patent Infringement

Last week, the U.S. Supreme Court held oral argument on
Bowman v. Monsanto Co.

Adam Liptak reported at the NYTimes.com in Supreme Court Hears Arguments in Bowman v. Monsanto.

It is clear from the questioning during oral argument that Monsanto will prevail on the merits, although it appears to this observer that many commentators underestimate the judicial and legal difficulty of this case, which the Supreme Court took on because it is the first time that the patent rights to progeny of a "self-replicated" product are being decided, i.e. whether successive generations of self-replicating seeds are subject to Monsanto patents on the "original" humanly and genetically-modified non-replicated seed.

Oral argument suggests quite convincingly that the Supreme Court will not rely on some kind of conditional sales doctrine as representing some form of restrictive "license" as a limitation on the first sale doctrine. As Justice Breyer said in this regard:

"Now, they -- they thought, the [Federal C]ircuit, that there's some restriction in a license and they have a doctrine that seems to say that you can restrict licenses -- through licenses the use of a product after it's been sold. And that would seem contrary to the first sale doctrine""

Obviously, the Supreme Court will be sure to set the Federal Circuit straight on its "lingering confusion" (quoting Justice Sotomayor) with respect to conditional sales. "Sales" have nothing to do with the coming decision per se.

Furthermore, the Court will also not rely on contractual limitations as the means by which patent holders must protect their rights. Patent rights as such are rights granted by the patents themselves, and not by contracts.

Rather, it is quite clear that the Supreme Court will hold that successive generations of self-replicating genetically modified and thus rightfully "patented" seeds are "copies" of the original patented seed, the "making" of which via unauthorized copies is prohibited.

Such a resolution as above of the legal problem presented by the case may appear by hindsight to be "apparent", but by no means necessarily obvious as a matter of law. Indeed, a strict view of the facts would hold that "God" makes the copies in the case of seed replication, regardless of genetic modification, even if human intervention (planting, fertilizing, watering, etc.) may also be required. In any case, the definition of "copying" here will be extended by the Court to its furthest possible limit for purposes of patent law.

It must be emphasized here in closing that the patents to the Monsanto soybeans involve the insertion of a genetic sequence into the germplasm of seeds that makes the resulting plants resistant to glyphosate, a herbicide manufactured by Monsanto, that otherwise kills other plants and weeds by inhibiting an enzyme necessary for growth.

When glyphosate is applied from the air, other plants and weeds in the field are killed while the resistant genetically modified plants survive and grow.

In other words, contrary to the situation in the upcoming Myriad case decision at the Supreme Court involving human genes, the "seed" here "created" by Monsanto has been truly "humanly" altered, even if the patent incorporates the original soybean seed or other plant seed as the object of the genetic modification. In Myriad, by contrast, there is the attempt to patent "cleaved snips" of actually existing human genes, and that of course will be denied by the Supreme Court, since the genetic code remains as is for its operative part, and is used principally as such, even if in abbreviated form.

In Monsanto there is a completely new addition to the genetics of the seed. In Myriad, one is merely using a genetics that is already there.

See the briefs to the Monsanto case at americanbar.org.

Myriad Patent Case Vacated and Remanded by U.S. Supreme Court in Light of Prometheus

Stanford Law Professor Hank Greely has a quick note in The Supreme Court Has Gavrilo’d the Myriad Case writing:

"Granted, vacated, and remanded in light of... Prometheus."

We previously posted about Myriad at Split Federal Circuit in Myriad Case Partially Reverses District Court and Finds Isolated Human Genes to be Patentable: Subsequent Supreme Court Review of this Case is Surely Essential.

This is really a toss of the ball back into the Federal Circuit's court, giving them a chance to apply Prometheus sensibly and, of course, to rule instead that isolated human genes are not patentable, which is and can be the only acceptable decision.

The logic we suggest is: if you cleave an orange in two, you can not claim the two orange halves as inventions, and so it is also with human genes.

Crossposted from LawPundit.

Prometheus Diagnostic Method Claims Not Patentable Says U.S. Supreme Court

Text below crossposted from LawPundit.

BRAVO to the United States Supreme Court! The unanimous (who would have believed that!) U.S. Supreme Court decision in Mayo v. Prometheus (and also the unanimous decision in Sackett vs. EPA) have restored our faith that the nation's highest court can be counted upon to see past the hype, spot the major legal issues facing the world, and decide them correctly. In the past, we have spent so much time at LawPundit battling against insanity in the patent sector (see here, here and here), that I am happy here just to pass along to you the following email which I received today. As a Paul, Weiss alum, I ask the people at Paul, Weiss to overlook my posting their letter in entirety, since the letter is covered by all kinds of copyright protection, but this is a very important case, and so it is probably better to let one of the world's top law firms give you the scoop, rather than my commentating it again from my admittedly biased point of view. The text of the Paul|Weiss email is given below, while the full text of the Client Memorandum summarizing the Prometheus decision (only 4+ pages in the memo, beautifully written) is accessible by clicking the link in that email:

Client Memorandum March 21, 2012

Paul, Weiss, Rifkind, Wharton & Garrison LLP

The Supreme Court Holds That Prometheus’s Diagnostic Method Claims Are Unpatentable Under 35 U.S.C. § 101 The United States Supreme Court issued a significant, unanimous decision yesterday in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (2012), holding that certain diagnostic patent claims were invalid for failure to recite patent-eligible subject matter under 35 U.S.C. § 101. The Court determined that the “steps in the claimed processes (apart from the natural laws themselves) involve well-understood, routine, conventional activity previously engaged in by researchers in the field,” and noted that “upholding the patents would risk disproportionately tying up the use of the underlying natural laws, inhibiting their use in the making of further discoveries.” In so holding, the Supreme Court reversed a Federal Circuit decision that the method claims were patent-eligible under the machine-or-transformation test, and do not impermissibly claim natural phenomena. The Supreme Court’s opinion is of interest to pharmaceutical and biotechnology companies because the decision leaves a large number of therapeutic and diagnostic patent claims vulnerable to challenge, especially those that concern correlations resulting from natural body processes. The Supreme Court’s decision states, however, that new drugs and new methods of using existing drugs remain patentable subject matter. And the decision suggests that certain patents covering diagnostic tests directed at the measurement of new or previously unknown analytes would withstand challenge under § 101. A link to the memo is attached. If for security reasons your e-mail system does not enable web links, please copy and paste the link into the address window of your Internet browser. http://www.paulweiss.com/files/upload/21Mar12SCOTUS.pdf      You are receiving this e-mail because Paul, Weiss, Rifkind, Wharton & Garrison LLP wishes to keep you informed of important and current legal issues. If you would like to unsubscribe, please e-mail us at news@paulweiss.com, and we will remove you from our update correspondence list. You may also write to us at: Attn: Practice Development Department Paul, Weiss, Rifkind, Wharton & Garrison LLP 1285 Avenue of the Americas New York, NY 10019-6064

New York | Beijing | Hong Kong | London | Tokyo | Toronto | Washington, DC | Wilmington

Copyright 2012, Paul, Weiss, Rifkind, Wharton & Garrison LLP. In some jurisdictions, this communication may be considered attorney advertising. Past representations are no guarantee of future outcomes.

Stanford Law Prof Greely Blogging on Obamacare Oral Arguments Before the U.S. Supreme Court: Day One

Professor Hank Greely of Stanford Law School is blogging at the Law and Biosciences Blog on the oral arguments before the U.S. Supreme Court, Day One.

He is suggesting that the court will find that the Anti-Injunction Act will not apply, prohibiting as it does, cases on taxes to be brought to the courts before the tax has been assessed.

This issue should not be underestimated because the U.S. Supreme Court can not permit a situation where every time some political faction does not like a new law of Congress, they turn to the Supremes.

Now, it is clear that Obamacare is not a direct tax, but there is in our mind no question that the Affordable Health Care Act is a form of indirect taxation and passed as it was to spread the costs of health care more equitably and to make affordable health available for all.

Hence, after all is said or done, it is not guaranteed that the court will not rule this an indirect tax to which the Anti-Injunction Act applies.

The Court has to be careful that it is not put into direct confrontation with Congress, indeed, be put in a position of second-guessing Congressional legislation before the actual act of implementation. Simply put, you have to have a harm to allege a harm. You can not be theorizing about the future.

We agree with Greely that that the Anti-Injunction Act will be held not to apply because this is not a direct tax, but also agree that if the Court can not reach a sensible consensus on the merits, they will always have this option available as an escape hatch.

Even if the Court does not use this escape hatch, they should direct some strong words at all the people who are pushing this case for POLITICAL reasons rather than actually being concerned about the Act's Constitutionality, which has been raised merely as an excuse to challenge legislation that is not liked by one political extreme.

A Supreme Court acting as a political referee would be in deep trouble down the road.

Congress, for better or worse, makes the laws, not the Supremes.
Hence, the Supreme Court Justices can not play legislator here.


Crossposted from LawPundit.

Law and Science Combined in a Career: Biotech Patent Law

William J. Simmons has the real deal at the journal Science in discussing the intersection of law and science as a career:

In Person: A Career in Biotech Patent Law - Science Careers - Biotech, Pharmaceutical, Faculty, Postdoc jobs on Science Careers.