Immunocompetent

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.

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]

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?

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.