H 1
Genes as Intellectual Property
Email Kathy


Patents: Genes as Intellectual Property
Notes from Dr. Marrs; Guest Speaker Lynn Tyler
Nov 18, 2009


"The abuse of frivolous patents is likely to cause more inconvenience than is countervailed by those really useful.' -Thomas Jefferson

 

I. What is Intellectual Property (IP)? (From WIPO)
I
ntellectual property (IP) refers to "creations of the mind": inventions, literary and artistic works, and symbols, names, images, and designs used in commerce.


Intellectual property is divided into two categories:

  • Industrial property, which includes inventions (patents), trademarks, and industrial designs; and
  • Copyright, which includes literary and artistic works such as novels,poems and plays, films, musical works, artistic drawings, paintings, photographs and sculptures, and architectural designs.

In the US, IP can be protected via the USPTO - the US Patent & Trade Office, Washington DC

  • Under U.S. law, a patent can be granted to "anything under the sun that is made by the hand of man."
  • Patenting does not equal "owning" - patenting means that your IP is protected from use or commercialization by others, unless you decide to license or cross-license your IP & work out a suitable arrangement (royalties, etc).
  • A patent provides a temporary commercial benefit to the inventor.
  • A patent also encourages technological progress by offering incentives to commercialize the invention and therefore benefit society.
  • Jon W. Dudas currently serves as Under Secretary of Commerce for Intellectual Property and Director of the USPTO.  He was nominated by President George W. Bush in March 2004 and appointed in July 2004.

II. A Real Quick History on Genes as IP:

The key legal foundation that laid the groundwork for gene patents: Granting a patent on a living organism, 1980.

Diamond vs. Chakrabarty 4,259,444 (March 31, 1981) "First patent on a living organism, a genetically engineered bacterium that digests oil spills. The USPTO originally rejected the patent, because it was on a living being, but the U.S. Supreme Court ruled that the bacterium was eligible for a patent because it had been genetically altered, and was therefore new, not obvious, not in its natural state, and useful for research. [PDF]

Shortly after that (1987) the USPTO ruled that “nonnaturally occurring nonhuman animals” are patentable. In 1988, First US animal patent was issued for The Harvard "OncoMouse”- genetically altered to be susceptible to breast cancer

Patenting human genes came shortly after: [Living Things (All Rights Reserved) Ricki Lewis]
(See 'Biotech Patent Hall of Fame' below)


III. Genes as Intellectual Property: How?!

Over 2000 patents on genes have been issued (See below). Keep in mind that the patent issued is NOT for the gene itself, but for the gene sequence, or the way the gene was found, or the utility of the gene. (No one can get a patent on your gene or anyone else's. A copy of your gene made in a lab is another story...)

Or, as William Hazeltine, former Pres of HGSI says: "Trying to patent a human gene is like trying to patent a tree. You can patent a table that you build from a tree, but you cannot patent the tree itself."

To be patentable in the U.S., a gene sequence, just like any other IP / invention must fulfill three requirements.

  1. It must be novel (new) - has it already been described in print (or patented)
  2. It must be non-obvious - to a person 'having ordinary skill in the area of technology'.
  3. It must have use (utility) - must 'operate or perform its intended purpose'.

Gene/EST/cDNA sequences fit these requirements because....

  1. New: The gene/ESTs/cDNA sequences have been isolated by automated processes, often randomly. A biotechnology company that has developed a particular process for isolating sequences can patent both the process and the sequences it finds. If the gene sequence has not been previously discovered, this satisfies the requirement of novelty.

  2. Non-Obvious: The gene/EST/cDNA sequences are not obvious in the human body, only in the lab - because they were made in the lab, and not in the body.

  3. Utility: IN 1994, the USPTO relaxed the utility claim (from 'substantial utility' or 'practical utility' to just 'utility', allowing very broad definitions of utility for patenting of living organisms and gene sequences (ex: ESTs are useful because they can find other ESTs or other gene sequences). As a result, few gene patents were rejected for lack of a utility claim. (Originally, going back to the 1770s, all that the law required was that the invention should not be 'frivolous or injurious to the well-being, good policy, or sound morals of society'!) So...genes fit, don't they?!

Just recently (2001), the USPTO has decided to tighten the utility requirement: The new utility requirements have three parts, and require that patent applicants show

  • specific utility (the applicant has to know what the gene does)
  • credible utility (the claim must be believable based on current state of the art)
  • substantial utility (the sequence must have a real-world use, such as use as a diagnostic or a treatment for a disease)

In the past, patenting of a gene sequence was allowed based on general claims such as using the sequence as a probe; now, such a general claim would be insufficient. .


IV. Genes as Intellectual Property: Why?

Q: Why would someone want to patent a gene sequence?
A: "Because no one would develop a drug if you didn't have a patent. Without the possibility of recouping the $500 M investment and years of commitment to get a drug to the market, no biotechnology company would be able to raise the financing necessary to develop these products" The Case for Gene Patents by William Haseltine HGSI

  • In an ideal situation, a patent promotes cooperation because the inventor is protected from exploitation, compensated for use of their invention, & therefore does not have to keep their invention secret - can even 'advertise' what they have to offer (This is one function of a Tech Transfer Department at a University) .
  • The flip side of that, of course, is that the inventor can (and often does) just as easily 'assert their rights' and refuse requests for use, retaining an exclusive license for 20 years. This is their legal right, whether it is socially responsible or not.

From Former USPTO Director Q. Todd Dickenson

  • "On the one hand, without the funding and incentives that are provided by the patent system, research into the basis of genetic diseases and the development of tools for the diagnosis and treatment of such diseases would be significantly curtailed.
  • "But at the same time, it is not the patent office's job to police the availability of innovations.
  • "Clearly, inventors and owners of genomic patents need to be acutely aware of the heavy responsibility inherent in that ownership; their licensing and other technology transfer practices need to strongly account for the powerful public desire to ensure that the use of these inventions for the greater good of all humankind is not unduly burdened."

 


V. Genes as Intellectual Property: Who!

Note: Although there are over 3 MILLION patents filed on ESTs, very few have actually been issued due to difficulty in demonstrating utility.

As of 6/2000, well over 2,000 patents have been issued to various companies (see The Great Gene Grab)

Incyte Genomics 297
University of California 253
Glaxo SmithKline 248
U.S. Dept. of Health & Human Services (NIH/NCI) 205
Human Genome Sciences 196
Genentech 165
Isis Pharmaceuticals 146
Chiron 135
American Home Products 130
Novartis 128

Slightly different list: According to Price Waterhouse, in the Washington Post 10/17/01 Top Gene-Related Patent Holders:

U.S. Dept. of Health & Human Services (NIH/NCI) 388
Incyte Pharmaceuticals 356
University of California 265
SmithKline Beecham 256
Human Genome Sciences 179
Eli Lilly 175
Genentech 172
Isis Pharmaceuticals 150
Chiron 149
American Home Products 137

[Whatever the numbers are TODAY, the scary but true fact remains: "There is one human genome and a finite number of genes" Mark Boshar, MLNM.]

 

Danger: Watch out for 'Submarine patents' - a slang term for patent issued on a very broad claim or on a gene whose function has not yet been determined that surfaces when another inventor's work gives the gene a function or identifies a commercial significance for the invention. The original patent holder of course demands big $$ or takes the new invention off the market.

  • University of Rochester Cox-2 inhibitor patent 4/ 2000 ("Historic drug patent is likely to be the most lucrative in U.S. history"!) U.of R. was issued a broad 'method-of-treatment' patent vs. Pharmacia and Serle's 'compound' patent on the Cox-2 inhibitor and anti-arthritis NSAID Celebrex. "The patent entitles the U of R to royalties on the sale of all Cox-2 inhibitors, made by Searle and Pfizer. Over the 17-year life of the patent, royalty payments could yield the U of R royalties in the billions of dollars, making it the most lucrative pharmaceutical patent in history."
  • Ooh, ouch: March 5, 2003 University to Appeal Ruling in Patent Case Against Pfizer and Pharmacia. A New York judge denied the University of Rochester's patent claims over COX-2 inhibitors like Celebrex (Science, 14 March 2003, p. 1638). The judge ruled the Rochester patent invalid because it did not show how to specifically inhibit COX-2 and not meet the law's standard for "written description" of the invention, because the patent did not describe a COX-2 inhibitor.
  • Ooh, extra painful (2005): Withdrawal of Vioxx (Oct 2004), Bextra (2005) = April 2005: All prescription-strength NSAIDs (including Celebrex) will now display “black box” label warnings for the potential risk of cardiovascular events and gastrointestinal bleeding...

  • Another painful submarine patent: Chiron vs Genentech for Herceptin (6/00) A submarine patent application that worked its way quietly through the patent office since 1984 = patent has been awarded to Chiron. Among the patent’s claims is the invention of a monoclonal antibody that binds to a cell surface receptor called c-erbB-2, also known as HER-2, the same target that Genentech’s Herceptin binds. Chiron filed first, thus is probably entitled to substantial royalties. Ouch!
  • Round II: resolved in favor of Genentech Federal jury supports Genentech in Herceptin patent case 13 September 2002
  • Another submarine patent ...ok...just kidding...I'll stop now...

Mudslinging:


Biotech Patent Hall of Fame: (just a brief list = lots more out there!)

 

(1) Diamond vs. Chakrabarty 4,259,444 (March 31, 1981) "First patent on a living organism, a genetically engineered bacterium that digests oil spills. The USPTO originally rejected the patent, because it was on a living being, but the U.S. Supreme Court ruled that the bacterium was eligible for a patent because it had been genetically altered, and was therefore new, not obvious, not in its natural state, and useful for research.

(2) The Cohen-Boyer patent "Process for producing biologically functional molecular chimeras" Dec 2, 1980 "The most-successful patent in university licensing, in the entire history of university licensing, is the Cohen-Boyer patent". As of February 13, 1995, licensing agreements had generated $139 million in royalties, which have shown an exponential increase in value since their beginning. In 1990–1995 alone, the licensing fees earned $102 million" Also, "The Cohen-Boyer patent is considered by many to be the classic model of technology transfer envisaged by supporters of the Bayh-Dole Act, which was intended to stimulate transfer of university-developed technology into the commercial sector. ". For patent, see 4,237,224


(3) Patenting Gene Sequences: Early '90s Craig Venter: Stirring things up at the NIH by trying to patent ESTs. He and Bernadine Healy recognized the utility of EST patents but everyone else was pretty darn upset about the idea...

"Genome Patent Fight Erupts", v 254 Science 184 (1991)
"NIH Gene Patents, Round Two", v 255 Science 912 (1992)
"Genome Project Goes Commercial", v 259 Science 300 (1993)
"NIH Drops Bid for Gene Patents", v 263 Science 909 (1994)

Dr. Healy testified at the infamous 'Sequencing can be done by moneys' Senate hearing that "When NIH does move into the patent arena it is with the public good as a driving force and not because scientists want to get rich. The real concern would be if a big pharmaceutical company got all of the gene patents". At the time Incyte had already announced plans to file patents on 10,000 genes....

(3) PCR - Kary Mullis: Process for amplifying nucleic acid sequences 4,683,202, July 28, 1987 [PDF]

'This is the foundational patent for polymerase chain reaction (PCR) technology, acknowledged as one of the most important and powerful tools of molecular biology of its time. The technology, conceived by Dr. Kary Mullis and patented by Cetus in the mid-1980s, has had enormous commercial success. In 1991 Cetus assigned its PCR patent portfolio to Hoffmann LaRoche for $300,000,000 and the worldwide market of PCR generates hundreds of millions of dollars annually in revenue from royalties'. Old history about the whole mess!

 

(4) The Geron Patents:

  1. Primate embryonic stem cells US Patent 5,843,780: (12/01/98)
  2. Telomerase US Patent 6,093,809: (7/25/00)
  3. Quiescent Cell Populations for Nuclear Transfer in the Production of Non-Human Mammals and Non-Human Mammalian Embryos US Patent 6,147,276: (11/14/00)
  4. Oocytes as recipients of nuclear transfer US Patent 6,525,243 (02/25/03)
  5. Methods and Materials for the Growth of Primate-Derived Primordial Stem Cells in Feeder-Free Culture Patent No: 6,800,480 (10/5/04)

(5) HGSIs patents, or, I mean to say...Gene Based Inventions

  • Direct links to all 571 of their ISSUED patents on human gene sequences! (Feb 2007)


Objectives:

1. Define IP and its two main categories
2.. What is a patent? What does a patent allow the patent holder to do?
3. What was Diamond vs. Chakrabarty and why was / is it a landmark Supreme Court decision?
4. How would a patent holder benefit from sharing his/her invention? Why might a patent holder choose to not share his/her invention?
5. What is a 'submarine' patent? Name two recent disputes involving submarine patents (No, not the 'patent on a submarine' example. But good try.)
6. Explain for a gene sequence meets all 3 criteria for patentability.
7. What is utility as it relates to patenting? How do the new utility requirements make it more difficult to patent gene sequences?
8. About how many gene sequence patents have been issued? Name at least 3 companies in the top 10-ish.

9. Know the basics of the top few in the Biotech Hall of Fame.

 

Schedule