Immunocompetent

More Notes from the WHO PIP IGM

perezoso — Thu, 11 Dec 2008 08:13:29 -0500

Here we continue notes from the World Health Organization Pandemic Inflluenza Preparedness Intergovernmental Meeting. Refer to the previous post to read: Pretending You are In Charge (WHO), America Insults the Scientists of the Developing World - Or Is It About Patents?, and Japan's Big Bluffer.

US Shenanigans on Distributing Vaccine Seed Strain

Uncle Sam is up to something untoward when it comes to WHO's (pre)pandemic influenza vaccine seed strains. Immuncompetent doesn't know for sure what it is; but he's got a hunch. The issue is the language under discussion that would direct WHO Collaborating Centres to distribute influenza vaccine seed strain.

In addition to providing H5N1 vaccine seed strain to industry (which WHO CC's presently do), most countries want to make sure that the vaccine seed strain is also provided to national influenza centers around the globe or, at least, in the country of origin of the HA gene used in the seed strain.

Although the US professes to be in favor of this, it actually seems to have problems with sharing vaccine seed strains. To wit, it insists on inserting qualifying language into the paragraph saying, in a limiting fashion, that vaccine seed strain should only be distributed "as broadly as possible". (Key words: "as possible".)

Asked what the heck it means by this, the US response was frankly unintelligble. The closest thing to something coherent that it said was the qualification is necessary "because we know there may be some restrictions upon us". Whatever the hell that means.

The US also keeps emphasizing that the recipient lab must have acceptable biosafety facilities and practices. Making this point, the US reminded everyone that "these viruses are highly pathogenic and deadly", so the vaccine seed strain could not be so easily distributed.

What? This is factually incorrect. That's odd, because the US usually gets its technicalities right.

Vaccine seed strains produced by WHO are attenuated (i.e. weakened). They are typically handled at BSL-2 containment. They are not deadly nor highly pathogenic like viruses found in nature because of their lab-adapted genetic backbone and/or altered HA gene. Sadly, the WHO Secretariat did nothing to correct the US - despite WHO having stated less than an hour before that its seed strains are attenuated.

So some biosafety capability (BSL-2) is needed; but the safety requirements are not nearly as stiff as the US claims.

What's up with this American nonsense about "as possible" and "deadly" BSL-2 vaccine viruses?

Immunocompetent thinks the US is looking for a back door in the agreement to raise security and patent issues - to permit it to impose export controls on influenza vaccines (like it presently does for Cuba, North Korea, and some others) and/or patent protections on seed strain (an "additional procedure" that the US has contradictorily argued against). This may be why they don't want a clear obligation to share vaccine seed strain with developing countries. They may want to reserve the right to say no to some countries for political reasons (e.g. Cuba) and to make money for patent holders (an in, it's "not possible" to give you the seed strain because you won't pay royalties).

Immunocompetent could be wrong; but that's our guess...

Even if you don't buy this explanation for Uncle Sam's odd behavior, if you think about it, the US position is pretty retrograde nonetheless. There is really no valid reason to refuse to provide WHO vaccine seed strain to anybody who is able to use it to produce effective vaccines.

CDC Statutorily Prohibited from Being a WHO Collaborating Center?

perezoso — Sat, 06 Dec 2008 13:31:00 -0500

The Centers for Disease Control has a World Health Organization Collaborating Center (WHO CC) for influenza, but it may be unable to fulfill its duty to WHO because US domestic law prevents it from adequately sharing influenza viruses. The law is US export control legislation, and it requires that labs, including CDC, obtain a license from the Department of Commerce before sharing a number of disease agents.

This means that shipments of H5N1 to other countries require a license. For some countries, like Canada, obtaining a license is routine; but for many others, including many WHO Member States, tighter export controls apply. These countries are indicated in a list maintained by the US Department of Commerce called the Commerce Control List Country Chart.

(“CB” type controls generally govern H5 virus exports. These range from “CB1” to "CB3”, with “CB3” being the most restrictive. The exception are the extra "special" countries in the USG's eye, like North Korea or, much less probably, Cuba, who have country-specific - i.e. even more restrictive - export control regimes.)

Export controls have been sharply criticized by developing countries for being arbitrary and political, and for contradicting technology transfer obligations in international agreements.

The US Department of Commerce has authority to simply deny shipment of H5N1 virus to other countries, even if the virus was given to the WHO Collaborating Center at CDC by a National Influenza Center in another country. In other cases, the US Department of Commerce may insist that foreign labs comply with US-style security rules or that they even to try prove to the US government that they are not a security threat to the United States.

US domestically legislated procedures to obtain H5N1 are contained the Select Agent Rule. They include submitting the fingerprints and biographical data of researchers to the Federal Bureau of Investigation (FBI), periodic laboratory security inspections (ironically conducted by CDC itself), and a large number of mandatory physical security measures and procedures.

Other restrictions on H5N1 viruses under US law include a prohibition on foreign recipients of H5N1 viruses from US labs from transferring them to others. So, for example, if the WHO CC at the Centers for Disease Control is able to send an H5N1 virus to a foreign National Influenza Centre for research purposes, the CDC may require the NIC to not transfer that virus to anyone else, even another WHO network laboratory.

Such strict domestic legislation may be sensible in the US because of its severe domestic bioterrorism threat (for example, the 2001 anthrax letters that were produced at US government lab and sent by a US government scientist), however, they may interfere with the ability of the Centers for Disease Control to effectively function as a WHO Collaborating Center for Influenza and to abide by its WHO Terms of Reference, which require sharing H5 viruses internationally.

The WHO Pandemic Preparedness Intergovernmental Meeting (PIP IGM) should be careful to avoid allowing national legislation to stand in the way of WHO-approved virus sharing by WHO Collaborating Centers. Therefore the PIP IGM should ensure that WHO Collaborating Centers for influenza are not located in where domestic legislation conflicts with the Collaborating Center’s responsibilities to WHO Member States.

In the specific case of the United States, WHO Member States should seek a public assurance from the US government that the WHO CC at the Centers for Disease Control will provide H5N1 viruses and vaccine seed strains to all Member States with a WHO-recognized laboratory, without the imposition of any delays, denials, or additional requirements due to export controls or other national legislation.

Swiss-American Venture Claims Blood of Vietnamese H5N1 Survivors (and Much More!)

perezoso — Mon, 06 Oct 2008 13:06:37 -0500

Think antibodies might be useful to prevent or treat bird flu? Better get out your checkbook, because a company based in San Francisco says it owns all H5N1 antibodies, including all human (and some animal) antibodies against the critical HA gene of the H5N1 "bird flu" virus. The claims are made in an international patent application published on September 18th.

But wait, it gets even more disgusting: The company also specifically claims DNA (and amino acids) taken from at least 3 Vietnamese survivors of H5N1. The DNA, which encodes antibodies, is contained in human cell lines established from the victims' blood.

If granted, the patent application could have profound effects in limiting research on antibody treatments against the potentially pandemic H5N1 type of influenza. It could also earn its owners huge profits from the blood of 3 (or 4) Vietnamese persons who were nearly killed by the virus. Who exactly wants to profit? Well, one of the would-be owners of H5N1 antibodies and pieces of Vietnamese people is none other than a co-founder of Chiron and former Director of Novartis. Sadly, there is no remedial ethics class to which to send these perverted patent applicants.

The patent application (WO2008110937) was published on 18 September 2008. It was submitted by HuMabs LLC, a relatively unknown company in California. HuMabs is owned, however, by Synergenics, a private venture capital-type firm financed and led by William Rutter. A prominent figure in biotechnology, Rutter is known for co-founding the company Chiron and as a former Director of Switzerland-based life science giant Novartis.

The scientific lead of HuMabs, and the sole inventor indicated on the patent application, is immunologist Antonio Lanzavecchia, an Italian researcher who leads the Institute for Research in Biomedicine (IRB) located in Bellinzona, Switzerland.

The blood samples were collected in late 2004 and early 2005 at the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. Some details have been published about the H5N1 victims whose blood was used.

Two were men, 22 and 23 years old when infected. They were hospitalized 7 and 3.5 weeks, respectively. A third victim was a 26-year-old woman whose hospitalization was relatively short, at ten days. It is from her blood that the most promising antibody, called FLD21.140, was isolated. There is no published information about the 4th blood donor.

The collections were part of a research program sponsored by the UK's Wellcome Trust and conducted by Oxford University scientists, who maintain a Wellcome-sponsored research centre at the Hospital. The Oxford scientists say they obtained informed consent from the Vietnamese H5N1 victims, who were treated at the Hospital.

The blood samples were sent to US and Swiss researchers collaborating with the Oxford team at the US National Institutes of Health (NIH) and the IRB in Switzerland.

In research with mice, antibodies extracted from the blood samples proved highly effective against Vietnamese-type (Clade 1) H5N1 viruses and partially effective against other (Clade 2) H5N1 types. The antibodies target the HA (hemagglutinin) gene of the influenza virus, preventing or inhibiting infection.

In parallel, the Wellcome Trust public relations department facilitated media access to the Oxford team in Vietnam, and a feature article about the research appeared in the Times (London) in October 2006.

The Times author highlighted a charming 11-year-old girl who beat the odds and survived H5N1 and noted, with no apparent irony, that "H5N1 patients are often the rural poor, with no phone and little contact with doctors", and that several of the H5N1 victims interviewed were suffering ongoing financial crises as a result of their hospitalization. Nothing was stated in the article about patents and profits.

In May 2007, the HTD/Oxford/NIH/IRB team jointly published the mouse experiments, which were portrayed as a significant step forward in H5N1 research. The Wellcome Trust simultaneously put out a press release on 29 May 2007. A footnote to the press release stated "Worldwide rights to the antibody technology have been licensed to HuMabs, LLC, a US-based business with offices in Bellinzona."

Sixteen months later, in September 2008, the HuMabs/Lanzavecchia patent application was published by the World Intellectual Property Organization (WIPO). The application claims not only DNA from the 4 Vietnamese victims that encodes 11 specific antibodies, it goes much further.

It specifically claims that HuMabs has invented the DNA and amino acids of ANY human monoclonal antibody against ANY H5N1 strain including all monoclonal antibodies that target the HA gene. The patent application claims many variants of these antibodies, including any that has the same "complementarity determining regions" ("CDRs"). CDRs are short amino acids that help target the virus and fight infection.

With respect to Clade 2 H5N1 viruses, the patent application claims any antibody that can neutralize them -- animal or human, mono or polyclonal.

The patent application raises ethical questions for several reasons. It claims the DNA of H5N1 victims as property, potentially enabling profit from the sale of parts and products of the human body.

This concern is amplified by particulars of this case, specifically, the disparities between the reportedly poor Vietnamese H5N1 victims, and the privileged European scientist and wealthy US venture capitalist who are making the property claims. Details of the consent forms signed by the Vietnamese victims and what, if any, additional agreements exist have not been made public.

In addition, antibody treatments are generally expensive and difficult to reliably produce, formulate, and distribute, raising questions about who will have access to the treatment (if it works), particularly in the event of a pandemic.

Many developing countries, and particularly poor citizens thereof, already are unable to access H5N1 treatments due to high costs. Even if HuMabs attempts to make its high-tech treatment available, it may not be possible to produce this in the quantity and at the price necessary for it to be useful to most of the world's population.

Finally, there is the startling breadth of the patent claims -- to any H5N1 human monoclonal antibody. It amounts to a general patent claim on part of the human body -- any person's body.

Any person infected with H5N1 or who receives H5N1 vaccines will produce H5N1 antibodies. Thus, HuMab's patent claims DNA and natural products of all humans who have the misfortune of being exposed to H5N1 or the benefit of being vaccinated.

This patent application is the latest in a string of aggressive H5N1 claims by companies and government laboratories in the United States and Europe. These applications heighten concerns raised by developing countries that the present international system for sharing of influenza viruses (the Global Influenza Surveillance Network, under the World Health Organisation) is unfair, and that the benefits of influenza research should be shared fairly and equitably.

A WHO Intergovernmental Meeting on Pandemic Influenza Preparedness (PIP IGM) will reconvene in Geneva in November to continue negotiations on the reform of the WHO's Global Influenza Surveillance Network (GISN) which has been criticized for allowing the viruses and other samples it collects for public health to be used for purposes of private profit.

H5N1 Related Patent Activity: An Updated Overview

perezoso — Tue, 23 Sep 2008 10:39:26 -0500

Although some, like US and European governments, would like to pretend it isn't happening, it's no secret that there has been a huge increase in international patent applications claiming bits and pieces of H5N1 viruses and related vaccines and other treatments.

The overall trends can be monitored by searching on PatentScope, a free international patent application database published by the World Intellectual Property Organization (WIPO). If you are new to patents, it might be intimidating at first - patent talk is not plain English - but with a bit of experimentation, searching PatentScope is something anyone can learn to do.

There are three such searches that I have been monitoring for nearly two years now. The results aren't pretty, and they are getting worse. The tidal wave of H5N1 patent claims shows no signs of abating, and is on track in 2008 to meet or exceed 2007, which was already the biggest year of such patent claims on record.

The trend is clear: An emerging "patent thicket" threatens to impair H5N1 research and make vaccines and other treatments unaffordable. But don't count on the US or European governments doing anything about this - they're still in denial mode.

The first search is a simple query of the International Patent Classification for influenza vaccines (PCT Class A61K 39/145). This search includes seasonal and animal vaccines. Here's the result (click on the image to enlarge):

In 2007, there were 54 patent publications on influenza vaccines. (Patent applications are published months or even years after they are actually filed) In 2008, to date, 33 new patent applications have appeared. Over 36% of all applications since 1983 for influenza vaccines (118 of 326) have been published since 1 January 2006. If this isn't a hug increase in patent claims, what is?

The second search is a bit more specific. It is a search of the same patent class, except restricting the results to those applications that contain the term "H5N1" in the patent claims (a specific and most important part of the application). Understand that you can still patent an H5N1 vaccine without specifically mentioning H5N1 in the claims (e.g. a vaccine against all influenza A types); but the appearance of H5N1 in the claims gives some potential indication of the intent of the applicant:

Here an interesting thing to immediately note is that although H5N1 first appeared in 1997, there was only one patent application matching the search until 2006. There is recent dramatic growth in H5N1-related claims. In 2006 there were five claims, followed by eleven in 2007, and seven in 2008 to date. US and EU companies account for nearly all applications (see below).

The third search broadens the horizon beyond vaccines. It includes vaccines, medicines, diagnostics, genes, and pieces thereof wherein the term H5N1 appears in the claims. (Geeks: PCT Classifications A61K/P, C07H/K, C12N/Q, G01N.) Here again, there is a tremendous spike in patent claims:

The amazing thing here is that between 1983 and September 2008, 102 total matching patent applications were published, and of these applications, 83 were published after 1 Jan 2007. That is, more than 80% of the matching patent applications over the last nearly 25 years have appeared in the last 18 months.

And where do these patent applications come from? Hint: It's not the Indonesians that are making proprietary claims over H5N1 viruses, it's the Americans and Europeans. A whopping 53% of these patent applications originate the US, and most of the rest come from Europe. What little is left over primarily comes from Australia, Japan, and Singapore.

The results here speak for themselves. Developing countries like Indonesia are not the people trying to privatize H5N1. In fact, the real culprits of ownership claims over Bird Flu are the companies and government labs of Europe and North America.

Are CDC's PR Hacks Lying about Patent Claims?

perezoso — Wed, 27 Aug 2008 07:45:35 -0500

If secondary sources are to be believed, such as this one, then CDC's PR hacks have sallied forth with a pack of lies about their patent claims on Indonesian, Thai, and other H5N1 genes, which were first brought into the public eye by this blog.

There are two main arguments that CDC has been quoted to me as making with respect to my article and related items that have come out in the press. I will refute both of CDC's claims.

First, CDC is said to have rather remarkably claimed that they aren't part of the patent application. This is patent bullshit, as I will show. Secondly, and somewhat contradictorily, CDC's hacks are said to claim that the patent application is (to paraphrase), "for a vaccine and not a virus, so the Indonesian and other strains aren't claimed." This too is wrong. To demonstrate that, I will walk readers through the text of one of the (many) claims, so you can read it for yourself. The claims analysis is a bit tedious; but it's not rocket science. Wade through it, and you will be rewarded with a clear explanation of why CDC is wrong. We'll deal with the CDC arguments one by one:

First, CDC is said to have bizarrely claimed that they aren't part of the patent application. This would be a remarkable thing for the CDC hack to say, because CDC is indicated as a patent applicant on the first page of patent application (quoting directly):

APPLICANTS: THE GOVERMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES [US/US]; National Institutes of Health,, Office of Technology Transfer, 6011 Executive Blvd., Suite 325, Rockvillle, Maryland 20852-3804 (US) (All Except US).

THE GOVERMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES [US/US]; Centers for Disease Control and Prevention, 4770 Biford Hwy (K79), Atlanta, Georgia 30333 (US) (All Except US).

Clear as can be. Is there really a need to say more? There shouldn't be; but I'm afraid there is.

That's because an ancillary argument that the CDC hacks are said to be advancing is that the US National Institutes of Health (NIH) is really responsible for this and CDC should not be held accountable for its name on the patent.

Off the top, I find it very hard to believe that a patent application can be submitted in CDC's name without CDC knowing about it. But more importantly, this CDC red herring needs to be put into context. Both CDC and NIH are part of the US Department of Health and Human Services (i.e. the health ministry). CDC hosts the WHO Collaborating Centre, and both it and NIH conduct flu research. And while it is true that most of the inventors listed in the application are from NIH, it's more than slightly disingenuous for CDC to try to beg off by foisting the blame on its HHS sister institute. In the international context, it's simply not credible to have one half of the health ministry (CDC) saying "no patents", while it is passing the material to the other half of the health ministry which is patenting away. So, in many senses, whether it is CDC or NIH or both is immaterial, because they are ultimately part of the same organzation (HHS) that has a WHO Collaborating Centre.

Turning to the claims analysis: CDC's hacks are said to have claimed that the patent application is (to paraphrase), "for a vaccine and not a virus, so the Indonesian and other strains aren't claimed."

The government spokesman bullshit detector of anyone with a whit of common sense would start ringing loudly just looking at the cover page of the patent (click it), which has an illustration of a genetic construct, claimed in the patent, that incorporates the "codon optimized" HA gene of A/Indonesia/5/05. It even says so right on the picture.

Could it be any clearer? Not really; but just be sure, we can turn to the most important part of patent, the claims, where the applicants specifically articulate the alleged invention that they are seeking patent for. Typically (but not always), the first claims are the most important in a patent. Let's turn to Claim 1 of the CDC/NIH application:

	WHAT IS CLAIMED IS:

		1. A nucleic acid molecule comprising a polynucleotide encoding an influenza
	protein selected from the group consisting of hemagglutinin A (HA),
	neuraminidase (NA), M2 Protein, and nucleoprotein (NP), wherein said
	polynucleotide comprises
			 
	(a) a plasmid taken from Table 1 (or its insert), or
			 
	(b) an analog of said plasmid or insert having at least 95% identity thereto.
	 
	
The first thing to note about this claim is that it is a claim on matter. That is, it is not merely a claim on the use of a particular type of matter (not that that would make it innocuous), it is a claim to the thing itself, full stop. Specifically this claim is for any polynucleotide (i.e. DNA or RNA) that encodes specific polypeptides (i.e. proteins), including some specific HA, NA, M2, and NP genes from influenza. And for good measure, anything 95% or more like them.

But which specific DNA or RNA is claimed, it's not spelled out explicitly in the quote above? Good question.

And what does that phrase "or its insert" mean? Another good question.

If you read the claim again, you will see that determining what specific DNA / RNA is claimed requires referring to "Table 1", and looking at the patent text in order to establish what "insert" means in the context of this patent application.

The meaning of insert can be quickly clarified. It is this: The plasmids refered to in Claim 1 are longer DNA constructs designed as vaccines, and which are pieced together with genes from multiple organisms. The picture on the cover page (click above) is one of these plasmids. The "insert" is/are the influenza pieces that are placed into the longer plasmid. Mostly "codon optimized" HA genes that have been copied into DNA from the viral RNA.

So, what's specified in Table 1? I have extracted Table 1 from the patent application, and you can click here to read it yourself (PDF format). It is 6 pages long, and includes no fewer than ~~151~~ 150 separate genetic constructs claimed by NIH/CDC, most of which are either "plasmids" or "inserts". (Remember that the plasmids are claimed in their entirety, including the inserts... which are also claimed apart from the rest of the plasmid.)

If it's a plasmid or an insert in Table 1, then it is claimed. On the first of the 6 pages of Table 1, there are 8 different constructs incorporating Thai H5N1 genetic material and one plasmid incorporating (i.e. with an "insert") of Indonesian genetic material. On the second page, there are 4 more constructs with Thai material. On the third page, there are 6 plasmids with Chinese (Hong Kong) genetic material, 2 with sequences from South Korea, and another Thai one. On the fourth and fifth pages there are 8 more with Thai genenic material. On the sixth page, there are 2 constructs with Thai genetic material, 6 with Hong Kong genetic material, and 2 with South Korean genetic materials.

The Indonesian construct ("VRC 9123") is the first listed and is the exemplary construct of the invention. Also, because the Indonesian HA gene is an "insert", it is claimed both as part of the VRC 9123 plasmid and by itself, alone. The same holds true for the other H5N1 inserts in Table 1.

Then NIH/CDC goes a step further, and says anything 95% or more like those genes is also claimed.

I hope that clarifies the nature and scope of CDC's patent claims. If CDC representatives have been accurately quoted as saying that they are not part of the patent application and that the application in any event does not claim Indonesian (and other) H5N1 materials, then the CDC representatives are spreading clearly false information, and the leadership of CDC should be reprimanded for permitting them to do so.

[Edited for clarity - 27 Aug PM]

Gene Squatters Claim the Next Pandemic

perezoso — Tue, 19 Aug 2008 13:15:46 -0500

If you think oil speculators are an ethically-challenged crowd, consider pandemic squatters. There are many examples. For one of the ugliest and most audacious, we turn to Finland.

Finns are usually an inoffensive lot, but it seems that a few of their number are hoping for the big one to come. A big pandemic, that is. And they're putting their money on H5N2. Helsinki-based Remedal, a tiny company with no apparent independent R&D capacity, has filed for patent on basically all injected or intranasal human vaccines containing an H5 and an N2 antigen (i.e. against H5N1 recombined with 'normal' human H3N2).

For good measure, Remedal further specifically claims such a vaccine using three HA genes that are WHO GISN materials: A/Hong Kong/213/2003, A/Vietnam/1194/2004, and A/Vietnam/1203/2004.

So, Remedal hopes, if an H5N2 recombinant goes pandemic (or seriously threatens to), it will own rights to the vaccine - and make a fortune. Some might vainly hope that we can have confidence that the patent authorities weed out this kind of application, but that would be an unfounded hope, because lousy patent applications issue all the time.

It's clear that the company has no ability to develop and market a flu vaccine. It's only announced compound is a "dietary supplement" that it says aids alcohol metabolism, reducing hangovers and liver damage. Even there it is looking for somebody to buy and commercialize the compound. Remedal of Helsinki is not about to provide the world with pandemic flu vaccine, although it is ready to claim a royalty on every shot if its gamble on H5N2 pans out. (And probably file a patent infringement lawsuit against anyone selling an H5N2 vaccine, driving up the price for everyone.) Worse than Roche and Tamiflu. At least Roche makes something. (No comment here on the perverse incentives to crime that issuing such patents might generate.)

Part of what's going on with this kind of patent squatting is an intellectual property system in dire need of reform, which goes well-beyond the H5N1 issue. But WHO's blind eye cast on pandemic influenza vaccine patents is a big problem too. When pressed to acknowledge intellectual property issues at all, WHO usually apologizes for whatever is the status quo. Its stockpile effort to date is a good example. WHO should be out there drawing a public health line around claims on pandemic vaccines and, in particular, patent claims on WHO GISN materials. If that were the case, then the GISN's crisis wouldn't be nearly as severe, and attempts at unethical pandemic squatting would be reduced.

CDC lays claim to Indonesian (and other) Flu Genes

perezoso — Tue, 12 Aug 2008 15:04:36 -0500

It would be hard to be more "in your face" than what the US National Institutes of Health and Centers for Disease Control are doing with patent claims to their new H5N1 DNA vaccine.

But right there on the front page it's laid out in black and white:

US GOVERNMENT SAYS INDONESIAN H5N1
VIRUS IS NOW THE PROPERTY OF UNCLE SAM.

Well, it doesn't literally say that; but this graphic appears:

The vaccine that is the exemplary embodiment of the invention contains the HA gene of A/Indonesia/05/05 and/or the NA, M2, and MP genes from the same strain.

How the CDC, which is a WHO Collaborating Centre, can simultaneously:

a) Claim it is not patenting WHO materials; and,
b) Blast Indonesia for "harming global public health [security]"; and,
c) Patent Indonesian viruses,

is one the miracles of modern scientific doublespeak. Talk about two-faced! No wonder Jakarta is hopping mad. But it gets even worse...

Get this: Adding insult to injury, the patent application designates Indonesia as a country where the US intends to pursue the patent. The CDC - a WHO Collaborting Centre - patenting an Indonesian virus in Indonesia. (As a practical matter, patent applicants dont always follow through on these country designations, but one never knows...)

And: The patent application claims similar DNA vaccines built around Thai, Chinese, and Korean H5N1 strains.

Needless to say, Uncle Sam will not be sharing patent rights and writing royalty checks to Indonesia if this works, nor will Indonesia have a say in where and how and at what cost the company that actually produces this (if it works) sells the vaccine.

It's difficult to imagine that a company would want to sell the vaccine to poor Indonesians when it can extract top dollar from rich Americans and Europeans if a pandemic comes.

Bottom Line: Indonesia gave WHO the virus, the CDC and NIH are patenting the virus, and Indonesia is S.O.L. when it comes to benefits.

Here's the full front page:

Say you're the Indonesian Health Minister. Do you think you're getting a fair shake?

Flu Patent Claims: What planet do some people live on?

perezoso — Tue, 12 Aug 2008 09:13:19 -0500

What planet do the people who claim that flu vaccines aren't patented live on? If they lived here on earth, then a quick search would tell them that there are numerous patent claims on H5N1 and other flu strains, frequently on viral sequences used in possible vaccines.

This morning I ran a quick a search on the World Intellectual Property Organization's PatentScope database for patent applications on (all) influenza vaccines. (Nerds: Int'l Class A61K 39/145.) The graphic above illustrates the result.

Yes, earthlings, there is a huge spike in patenting of influenza vaccines. A lot of it has to do with the move away from egg-based technology, in part because of the particular difficulties presented by H5N1.

But do some of these patent claims actually grab virus genes that were sent to the WHO system? You bet they do.

One of the worst offenders, MedImmune (now part of AstraZeneca), has claimed dozens of H5N1 sequences as its "intellectual property". To show that, I'm including here a page from one of MedImmune's patent applications indicating sequences it claims.

Vaccine patents will be frequent topic at this blog and this post is just to introduce the theme. For a more comprehensive analysis prepared last year, you can click here (PDF download). But patents are moving so fast, even that 2007 paper is now dated. There are dozens more patent applications out there now.

A Glance at Current H5N1 Vaccine Trials

perezoso — Mon, 11 Aug 2008 16:06:14 -0500

More than five dozen clinical trials for H5N1 vaccines have been registered in the US in recent years. A listing of trials (which includes many taking place outside the US) is available here.

Here is a quick review of many of those that are either ongoing or preparing to recruit human subjects, emphasizing those that relate to new biologicals (and less on studies primarily concerned with adjuvants):

GLAXOSMITHKLINE

Efficacy studies in the US and Canada, involving more than 5000 adults, of an experimental split virion H5N1 vaccine denominated 1557484A. This is a monovalent A/Indonesia/5/05 based vaccine.

Efficacy studies in Spain, Taiwan, Italy, Belgium, Hong Kong, Singapore, and Thailand of another experimental split virion H5N1 vaccine denominated 1562902A. The composition of this H5N1 vaccine is not stated.

SANOFI

A US safety and efficacy study of experimental monovalent formulations of its H5N1 vaccine, with the goal of reducing the required dosage. The exact composition of the H5N1 vaccine is not stated, although Sanofi's licensed H5N1 vaccine uses A/Vietnam/1203/2004.

A safety and efficacy study in Belgium and Australia of an experimental split virion H5N1 vaccine. (Related studies in Belgium and the UK assess the efficacy of adjuvants used in the vaccine.)

Further testing an H5N1 vaccine in infants and children in Thailand.

SOLVAY

Trial involving 400 adults in Finland and Germany of various formulations of an egg-based H5N1 vaccine. The exact composition of the H5N1 vaccine is not stated.

BAXTER

Safety and efficacy trials underway of a cell culture-produced killed whole virion vaccine, using A/Vietnam/1203/2004. Some study participants receive a booster shot containing A/Indonesia/05/2005. The studies are taking place in Austria and Germany.

Safety and dosing trials underway in Hong Kong and Singapore of a double-dose cell culture-produced killed whole virion vaccine. The exact composition of the H5N1 vaccine is not stated.

Large study, in 9 European countries, of a cell culture-produced killed whole virion vaccine, using A/Vietnam/1203/2004.

NOVARTIS

Multiple safety and efficacy and dosing trials of H5N1 vaccines that use (or not use) its MF59 adjuvant. This set of trials are in Italy. Exact composition of the vaccine not stated.

Safety trial in Colombia of an H5N1 vaccine in combination with a Southern Hemisphere trivalent seasonal flu vaccine. The exact composition of the H5N1 vaccine is not stated.

Safety trial in Germany of a combination seasonal (presumably North) and H5N1 tetravalent vaccine (i.e. with a total of 4 antigens). The exact composition of the H5N1 component of the vaccine is not stated.

A safety and efficacy trial in the UK of multiple doses of an H5N1 vaccine in combination with/without various combinations of a seasonal (presumably Northern Hemisphere) vaccine and a proprietary adjuvant. The exact composition of the H5N1 vaccine is not stated.

Further testing an H5N1 vaccine in infants and children in Finland.

NOVAVAX

A US safety and efficacy trial underway of its virus-like particle vaccine. The viral source of the VLPs is not specified.

US CENTERS FOR DISEASE CONTROL

A safety and efficacy trial of H5N1 vaccine (exact composition undisclosed), in 100 adults at occupational risk of exposure to live H5N1 viruses. Location unstated.

US NATIONAL INSTITUTES OF HEALTH (HAS COLLABORATION WITH MEDIMMUNE / ASTRAZENECA)

A dose comparison trial of an A/H5N1/Indonesia/05/05-based vaccine in adults who were previously vaccinated with an A/H5N1/Vietnam/1203/2004-based vaccine.

A US dosing trial administering 9 different vaccine formulations using A/H5N1/Vietnam/1203/2004 and/or A/H5N1/Indonesia/05/05.

Plans to enroll 155 US adults in a study that will inject them with a high dosage of an (undescribed) H5N1 vaccine in order to stimulate the subjects to produce high levels of antibodies to the vaccine strain. These antibodies are then collected and used in efforts to produce an immune globulin flu treatment.

Plans to enroll 44 US adults in a safety and efficacy study of a DNA plasmid vaccine delivered in a needle-free transdermal system. The exact composition of the H5N1 vaccine is not stated, although other sources indicate this lab has prepared DNA vaccine plasmids bearing the HA gene of A/Indonesia/5/05. A related study is injecting a DNA vaccine into 45 US adults.