PCR PATENT WARS

GROUP 32 ABHIMANYU ANCHA 129278042 PARICHIT DEV 129278107 SORABH GAMBHIR 129278108

INTRODUCTION
Polymerase Chain Reaction (PCR), molecular biology technique: small amount of DNA to be amplified exponentially Discovered, Developed, and Patented in industry settings Patents on biological tools could impede their dissemination and use PCR was protected with robust patent rights and heavily licensed PCR managed to disseminate IPR not prevented PCR from its widely use Initial period od secrecy in initial in house development phase

DISCOVERY AND DEVELOPMENT

Discovery of PCR technique Kary Mullis, a chemist won the Nobel Prize in 1993 for his work on PCR

Work in Cetus- synthesizing short segment of DNA

Experimented the denaturation/renaturation properties of DNA and quantify the properties of time and temperature on DNA Finally on December16, 1983 : the evidence of amplification of oligonucleotide with polymerase by increasing the cycle of denaturing/renaturing process Contact to Al Halluin, Cetus Chief Patent Councel Halluin contact to Cetus President; pursue it but not at expense of important things

DISCOVERY AND DEVELOPMENT

In June 1984, Mullis presented a poster presenting amplification of Beta globin gene at Cetus annual scientific meeting (Big time ignored) Cetus was biotechnology industry with limited resources, and mainly focus on diagnostics, cancer therapeutics and agriculture Development of PCR might detract them from their main goal Summer 1984, Mullis relieved from his duty and given one year trial period to focus PCR PCR group was formed for developing application tool for this technique PCR group almost perfected the technique (15 Nov 1984) but Cetus require developing not only publication strategies also the patenting and business strategies

DISCOVERY AND DEVELOPMENT

On 28 March 1985, First PCR process patents filed with USPTO Now Cetus shifted focus to dissemination of technology PCR application presented at the meeting of the American Society for Human Genetics In September 1985, PCR application paper submitted to Science

The strategy was patent first, then publish, now the focus shifted to commercialization

COMMERCIALIZATION
Strategic partnership with other cooperation: Others expertise for further development of the technology
December 1985, Cetrus (49%) enters joint venture with Perkins-Elmer (51%) to develop diagnostics instruments and reagents for use with PCR February 1986, Cetus enters with agreement with Kodak to develop invitro PCR diagnostics 28 July 1987, Patent #4683202 Process for amplifying nucleic acid sequence Patent #4683195 Process for amplifying and detecting and for cloning nucleic acid sequence Issued to Cetus

COMMERCIALIZATION
PCR diagnostics market was booming; more than 50 different organizations approached Cetrus for licensing PCR for diagnostic purposes

PCR diagnostic market worth $1.5 billion

November 1988, Cetus created entire division for development of PCR Division focus on business partnerships and licensing programs Cetus-Kodak partnership was set to expire in December 1988, Cetus was seeking ways to capitalize to more favourable offers and large sponsors like DuPont, Abbott and Hoffaman-La Roche

ROCHE-CETUS PARTNERSHIP
ROCHE CETUS

DuPont VS Cetus
In August 1989, Du Pont filed a case on Cetus, alleging core PCR patents were not novel
Process had been previously described in 1970 Cited work on Repair Replication by Dr. Gobind Khorana at MIT

On August 23, 1990, USPTO announced to uphold the validity of both patents
Repair Replication papers too indefinite and uncertain to have made PCR an obvious process

PCR OUTGROWS CETUS

Even increased sales from PCR, Cetus finished 1990 with $60 million
Cetus negotiated Roche would pay $300 million for sole ownership of rights to diagnostic uses of PCR On 23 July 1991, Chiron Corporation merge with Cetus in a estimated deal $660m On 11 December 1991, Roche acquired the rights to PCR from Cetus Cetus retained the rights to use PCR in the development of therapeutics

PCR LICENSING
To expand and commercialize, Roche formed a new subsidiary, Roche Molecular Systems to handle manufacturing and licensing od PCR rights Cetus had implemented agreements(RTLAs) the reach through licensing

Users pay royalties to Cetus on any invention or marketable product created by PCR This plan was met with harsh criticism

Roche announced new, less imposing PCR licensing strategy

Eliminated the up-front fee i.e., $15000 to non profit and academic Reduced the royalties on the sales of PCR based products as low as 9%

ROCHE VS PROMEGA
On 27 October 1992, Roche filed suit against Promega which covers nTaq polymerase use in the PCR reaction In 1990, Promega and Cetus entered into license, which granted the right to manufacture and sell the Taq polymerase for non PCR users Promega paid $30,000 up front costs and 10 % royalties of sales Roche claimed that Promega violated the agreement by manufacturing products that aimed customers to use them for PCR On 16 May 1995, Roche provide the court a list of 200 individuals, institutions using for PCR Roche said that they are suing the inducer, not suing the many parties that have been induced

ROCHE VS PROMEGA
The two arguments were made 1) invalidity 2) inequitable conduct Invalidity: Taq polymerase has been isolated by Chien and colleagues at University of Cincinnati Re-petitioned that enzyme isolated by Chien was fragments of enzyme Promega presented that Cetus did not perform side by side control experiments between the Taq enzyme and polymerase isolated by Chien Inequitable Conduct: Cetus intentionally deceiving UPSTO had obtained the patent by

In May 2004, the patent was invalidated and Roche could not recoup damages for breech of contract

ROCHE VS M.J. RESEARCH

In June 1998, Roche filed suit against M.J., claiming they had infringed 3 thermal cycle patents M.J. willingly selling to customers, who they know that they would use the machines for PCR Roche showed their website in which their thermal cycles were being adapted for PCR The jury found that wilfully infringed patents and awarded damages of total amount $19.8 million

EVALUATING EFFECTS OF IPR

Many argue that patents provide incentives for the costly research and development of new technologies
Patent protection may have been essential to spur on PCRs development within Cetus but hinder to use this technology by researchers Most complaints about licensing fee and royalties which made PCR expensive in some fields On 28 March 2005, expiration of key PCR process patent expected to open up new areas of research Strong patent rights are incompatible with widespread dissemination but in PCR the 3 key reasons that PCR had become so widespread Cetus/Roche s extensive use of licensing and business partnerships Fair and adaptable licensing strategies Ease of obtaining licenses

LEARNING
Complications can arise from earlier patents
Their validity can be challenged and patent rejected

Even with easy licensing terms, their can be parties that flout the norm

Knowledge

is important to society above and beyond its ability to generate a profit.