This article at the NY Times is quite disappointing. The author makes several unwarranted leaps, for example, comparing the cost of vaccinations in 1980 to today...

Getting a vaccination was not always so difficult. In 1980, it cost only about $23, or $59 adjusted for inflation, for the seven shots and four oral doses needed to immunize a child, according to data provided by Thomas Saari, who is emeritus professor of pediatrics at the University of Wisconsin.

Today, though, a child who receives all the recommended vaccines would receive as many as 37 shots and 3 oral doses by the 18th birthday — at a cost exceeding $1,600.

The 1980's were well before the biotech industry really existed (hell, recombinant techniques didn't even exist until nearly the mid-70's!); one would fully expect that vaccines developed before modern molecular biology would be technologically simpler and cost less to develop and produce. Plus we're not comparing the same thing... the above compares required vaccines in 1980 with all recommended vaccines today; when you include the newer, clearly useful, vaccines, you fully expect the price to increase. So the comparison is rather disingenuous.

Note that the argument isn't about whether or not the new vaccines should be mandatory; the Times article is mostly complaining about the cost of all recommended vaccines.

There is amongst some an expectation that any biological technology that can help people should be given away for nearly free. This attitude doesn't seem to appear in other sciences (who would expect carbon nanorods, or synthetic zeolite catalysts to be immediately affordable?). Why is biology so different?

If the fear-mongering segment of the public succeeds in taking the market out of the biological technology industry, there won't be one. Let's not get so breathless when drug prices are high, because it's worth remembering therapeutics will be cheap and abundant when their patents runs out.

It's instructive to remember that Rogaine, Claritin, Aleve, and even Tylenol were all once on-patent drugs...

Filed under chemistry · patents · science

Posted by H. C. Hodges at 4:16 PM | Permalink | Comments (0)

As you may recall from my previous post, a company called Ariad is suing Lilly & Co. over alleged infringement of a patent related to NF-κB activity. NF-κB is a protein which regulates inflammation and immune response in cells; as such, it is considered by many to be a great target for new drugs.

In my previous post, I expressed skepticism that the so-called 'Baltimore patent' will be upheld. I have since bothered slugging through some of the patent code (U.S.C. 35), and have refined my thoughts a little more.

One of the strongest arguments I can think of against Ariad is that the Baltimore patent had simply not reduced the claimed invention to practice. According to 35 U.S.C. § 112:

The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.

As an example, consider two fairly representative claims from the Baltimore patent:

1. A method of inhibiting expression, in a eukaryotic cell, of a gene whose transcription is regulated by NF-κB, the method comprising reducing NF-κB activity in the cell such that the expression of said gene is inhibited.

6. A method for diminishing induced NF-κB-mediated intracellular signaling comprising reducing NF-κB activity in cells such that NF-κB-mediated intracellular signaling is diminished.

Obviously creating a particular drug requires vastly more resources than claiming what amounts to a big-picture idea for a research project. The court will have to decide whether or not the Baltimore patent ever actually reduced to practice their claimed invention. It is a fundamental requirement that a patent describe an invention well enough for a person having ordinary skill in the art (of biochemistry, in this case) to be able to create and use the invention. This is what The People receive in exchange for granting an exclusive license to the inventor.

Furthermore, according to 35 U.S.C. § 102(g), Lilly need only show that it conceived of the two drugs and worked "with reasonable diligence" to create them before the priority date of the Baltimore patent. Lilly also has to show that it didn't "abandon, suppress, or conceal" those two drugs. Since Lilly claims it disclosed the medical properties of Xigris and Evista before the Baltimore inventors conceived of their idea, it will be very difficult for Ariad to show that Lilly had concealed Evista or Xigris before the Baltimore patent's priority date.

The courts must consider "not only the respective dates of conception and reduction to practice of the invention, but also the reasonable diligence of one who was first to conceive and last to reduce to practice." Lilly, it seems to me, need only prove that they worked with reasonable diligence to reduce their two drugs to practice, while Ariad and the patent holders have to prove that they have sufficiently disclosed their invention such that any skilled worker could create and use it.

As a fairly skilled worker in the art of biochemistry, I wouldn't have any idea where to start to create and use some of the claimed inventions in the Baltimore patent. It is pretty clear to me that the Baltimore patent has not sufficiently disclosed their invention; as such I continue to expect that the appellate court will decide for Lilly & Co. and set aside the jury's previous verdict.

Filed under biology · chemistry · patents · science

Posted by H. C. Hodges at 10:31 PM | Permalink | Comments (0)

Via the PHOSITA® intellectual property blog, a story about a machine that invents machines. Well, sorta.

In the same vein as my previous post about the singularity summit at Stanford, we hear the story of John Koza:

Now 62 and an adjunct professor at Stanford University, Koza is the inventor of genetic programming, a revolutionary approach to artificial intelligence (AI) capable of solving complex engineering problems with virtually no human guidance. Koza’s 1,000 networked computers don’t just follow a preordained routine. They create, growing new and unexpected designs out of the most basic code. They are computers that innovate, that find solutions not only equal to but better than the best work of expert humans. His “invention machine,” as he likes to call it, has even earned a U.S. patent for developing a system to make factories more efficient, one of the first intellectual-property protections ever granted to a nonhuman designer.

I hadn't heard of this guy before, but apparently he's fairly famous in certain circles. Not only did he help pioneer the use of genetic programming, he also co-invented the scratch-off lottery ticket. Naturally.

Read more: John Koza has built an invention machine.

Filed under california · patents · technology

Posted by H. C. Hodges at 12:00 PM | Permalink | Comments (1)

You may have heard recently in the news about the patent dispute between Ariad Pharmaceuticals and Lilly. Ariad had licensed a patent from Harvard, MIT, and Whitehead that covers use of NF-κB activity. This patent (No. 6,410,516), created by David Baltimore and colleagues, claims much about the NF-κB system — there are a total of 203 claims in the Baltimore patent.

While a patent can claim virtually anything, the patent office's examination should help rule out claims that will not be upheld in court. However, in general there is no guarantee that patent claims will be upheld unless they conform to certain rules. In particular, in the US patent system, patents must be:

• A patentable invention: patentable inventions are any new and useful process, machine, manufacture or composition of matter, or any new and useful improvement thereof.
• Novel: in contrast to the rest of the world, US patents are granted to the first-to-invent, not the first-to-file. The patent will be ruled invalid if the invention:
  • was invented previously by someone else,
  • was described in a US patent application that is later granted with an earlier priority date, or
  • was known or used by others in the USA or described in a printed publication in any part of the world.
• Non-obvious: One must convince the patent office that the invention would not be "obvious" to someone else with similar knowledge at their disposal.

(from Patents for Chemicals, Pharmaceuticals and Biotechnology, 4^th Ed., Philip W. Grubb)

The claimed methods as described in the Baltimore patent are to me of questionable specificity. The researchers discovered a process of nature, then patented many of the obvious theoretically possible therapeutic routes dealing with that natural process. While US patent law is sometimes a little vague about the novelty criterion, it is generally accepted that processes or phenomena of nature can not be inventions, but methods which harness natural processes are fair game. So is it obvious, after discovering NF-κB's natural function, that one could inhibit its activity for therapeutic benefit? That's perhaps a more nuanced question than it first seems, so I'll let you decide.

From what I understand, Ariad is suing Lilly because Ariad claims Lilly's Evista and Xigris drugs modulate the activity of NF-κB. In its response to the case, Lilly asserted that they had "discovered these drugs and disclosed their medicinal properties years before the patentees' scientists made their discovery." At first blush, I'm inclined to agree with Lilly, but I certainly haven't heard all the details of the case.

I suspect the patent will not be upheld on appeal. As a matter of commerce, if Ariad were to continue winning in court, most pharmaceutical research would come to a halt. This is really a test case, because if Baltimore, et al, can in effect patent the entire NF-κB signalling cascade, entire companies will stop small-molecule R&D out of fear of patent infringement.

However, before the courts is not a matter of commerce, but a matter of law. Although normally I think I would root for the scientists and academics, I think this patent just might be overly broad...

UPDATE: I almost forgot that about two years ago, a friend of mine had the pleasure of meeting David Baltimore when he was giving a talk down at Stanford. She got to drive him around campus on a little golf cart to take him to various labs, and said he told some great stories... Incidentally, Baltimore is now the president of Caltech, and Giao has his (actual) signature on her diploma. Sheesh it's a small world.

UPDATE: See also my more recent post: "Ariad v. Lilly, revisited"

Filed under biology · patents · science

Posted by H. C. Hodges at 8:51 AM | Permalink | Comments (0)

I've been reading the 4^th edition of Philip W. Grubb's Patents for Chemicals, Pharmaceuticals and Biotechnology, and so far, it's an excellent textbook. I would highly recommend it for those interested in the historical and philosophical developments of intellectual property rights in the biosciences.

This section on patents in developing countries caught my attention; I thought I would share an excerpt:

The entry into force of the TRIPs agreement in 1995 came at a time when the extent of the AIDS epidemic in Africa was becoming clear. Patented anti-retroviral drugs were being used in the USA and Europe to control the progression of the disease, but these drugs were very expensive and unaffordable for the vast majority of patients in developing countries. The perception arose, fostered by NGOs such as Médicins sans Frontières (MSF) and Oxfam, that patents were the reason why these drugs were not being made available to AIDS sufferers at an affordable price.

In fact, patents are not the problem. Not only are there no patents for most of these AIDS drugs in most African countries, there are also no patents in any countries for most of the drugs on the WHO Essential Drugs list—so why then are these essential drugs not readily available to patients in poor countries? The answer is simply lack of money to buy even cheap medicines, and lack of social and medical infrastructure to deliver them. The terrible truth is that if AIDS could be cured by a glass of clean water, there would still be millions who would have no access to the cure. Unfortunately, patents and the 'greedy' pharmaceutical companies make a much easier target than the miserly rich country governments and the corrupt poor country governments who together make up the real problem.

Despite the lecturing tone, Grubb succeeds in highlighting the asymmetric flow of criticism with regards to problems of the Third World. While it's common to hear that these problems stem from the actions of Wealthy Americans and Their Tool the WTO, we hear relatively little about the role of bad governance. Poor governance and lack of independent press consistently give rise to famine and abysmal social conditions (see: Zimbabwe), but few seem willing to confront this problem head-on. This brings to mind what I previously wrote regarding the whole Mohammed cartoon fiasco.

Grubb continues:

However, the pharmaceutical industry also did a lot of damage to its own image, notably by its legal action in the South African courts against the South African government over a proposed law for compulsory licensing of some pharmaceuticals. The proposed law was contrary to TRIPs and arguably unconstitutional, but the spectacle of the pharmaceutical industry suing Nelson Mandela (who was then still President, and was the first name on the list of defendants) in order to maintain control of drug supplies was a public relations disaster of the first magnitude.

Apparently, this debacle influenced the 2001 WTO meeting in Doha, as well as 2003 meeting in Cancun. This is quite an important story, because its outcome will affect how poor countries obtain access to pharmaceuticals. In particular, the result will decide whether poor countries obtain their drugs through legitimate or through illegal means.

One point of note is that if property rights for medicines were universally enforced, drug prices wouldn't be so high here in the U.S.A. Overseas manufacturers of cheap generics that infringe upon patents of pharma innovators are pirating intellectual property. Pharma piracy causes real damage to the actual innovators, because they lose out on income that would help recoup the cost of development; the result is higher drug prices for all and reduced investment in R&D.

In a global world, we are increasingly influenced by bad governance overseas. First World countries should be insisting on good government in the Third World. Unfortunately, the continuing legacy of colonialism makes things extraordinarily difficult.

Filed under culture · hiv · patents · science · textbooks

Posted by H. C. Hodges at 1:07 PM | Permalink | Comments (0)