Biotechnology: Invitrogen vs. Agilent

1. Biotechnology:Invitrogen vs. Agilent Patent Innovation Christine Chen 9/15/2008

2. (Biotech) Patents • In general, patents must be: • Novel (not known previously) genetic sequences • Non-obvious (not just a simple improvement) • Have a useful purpose so that someone in the field can use it by that stated way • State the sequence’s product • Specify how the product is used in nature

3. Background: Biotech Research -> Patents • Completion of Human Genome Project in 2003 • After completion, much of the federal government research transferred to the private sector. • Since then, US Patent and Trademark Office has issued a few patents for gene fragments. • ESTs are expressed sequence tags, making up 10-30% of cDNA, which are laboratory-made genes of the exon region (the expressed part of the mRNA) • ESTs allow researchers to directly study important biological regions

4. Background on Biotech Patents • DNA is not patentable in its raw form. • Only when DNA is isolated, purified, or modified is it patentable. • When a biotech patent is given, new invention is deposited in 1 of 26 worldwide culture depositories • 3-million genome-related patents have been filed • Sequences found in public databases may have been patented by private sector. Users could face injunction.

5. Controversy Over Patenting Gene Fragments • Some say patenting an EST find is of less importance than isolating the gene product, discovering its purpose, and making a commercial product • Allowing multiple parts on the same genome sequence makes it so that researchers who want to look at that sequence have to pay the patent holder to look at the sequence, which critics feel is unfair

6. Invitrogen’s case vs. Agilent • Invitrogen has mainly been the plaintiff in biotech patent infringement cases • Invitrogen is a $26 billion research tool industry- focus on genomics, cell biology, bioinformatics • Agilent is a tech leader in communications, electronics, life sciences and chemical analysis • Case: • June 2000: Invitrogen sued Strategene, which was purchased by Agilent in 2007, for infringing on 3 of Invitrogen's patents • Invitrogen filed these patents between 1993-2000 • All 3 patents have to do with a gene which encodes reverse transcriptase (RT) having DNA polymerase activity and substantially no RNase H activity, which is undesirable

7. Engineering Aspect • Reverse transcriptase contains at least two enzymatic activities, DNA polymerase and RNase H, that are on 1 polypeptide. • RT DNA polymerase activity is responsible for transcribing RNA into double-stranded DNA • function of RNase H in replication is less clear, but it is thought to degrade genomic RNA during DNA synthesis Reverse Transcriptase

8. Three Key Patents Involved in Case Continuations: extend the patent of an applicant’s patent info previously disclosed in parent patent #3 -> continuation of #1 • #5,244,797 (issued 1993) -polypeptide having DNA polymerase activity and substantially no RNase H activity • #5,405,776 (issued 1995) - isolated DNA encoding a polypeptide having DNA polymerase activity and substantially no RNase H activity • #6,063,608 (issued 2000) - isolated polypeptide having DNA polymerase activity and substantially reduced RNase H activity • RT is used extensively in recombinant DNA technology to synthesize cDNA from mRNA. One major problem with cDNA synthesis is that the RNase H activity of RT degrades the mRNA template during first-strand synthesis. • The invention is related to the discovery that portions of the RT gene can be deleted to give a deletion mutant having DNA polymerase activity but no detectable RNase H activity. This purified mutant RT lacking RNase H activity can be used to effectively synthesize cDNA from mRNA.

9. Result of Litigation • In February 2008, Invitrogen and Agilent settled patent infringement where Agilent agreed an undisclosed payment to Invitrogen. In return, Agilent had to stop sale of its RNase H minus reverse transcriptase products. • In a settlement of a separate case in November 2001 where Agilent sued Invitrogen for infringing on their patent, Invitrogen had to take out a license from Agilent for its DNA polymerase blend products and pay undisclosed royalty fees.

10. Invitrogen’s Stance on Patenting • "The patent system, as it presently operates, provides the incentive necessary to fuel the development of innovative and beneficial research tools by granting an inventor the exclusive right to control the use of his invention for a limited time.” -Invitrogen representative ------------------------------------------- • Law of intellectual property rests on an assumption that, without exclusive rights, no one will be willing to invest in research and development. -Human Genome Project site

11. References • http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml • http://www.ornl.gov/sci/techresources/Human_Genome/elsi/patents.shtml • http://www.labtechnologist.com/Industry-Drivers/Invitrogen-sues-GE-Healthcare-over-patent-infringement • http://en.wikipedia.org/wiki/Continuing_patent_application • http://tiger.gatech.edu/files/gt_tiger_patent.pdf • http://www.genengnews.com/news/bnitem.aspx?name=29953532 • http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6,610,522.PN.&OS=PN/6,610,522&RS=PN/6,610,522 • http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=5244797.PN.&OS=PN/5244797&RS=PN/5244797 • http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=5,405,776.PN.&OS=PN/5,405,776&RS=PN/5,405,776 • http://www.signonsandiego.com/uniontrib/20080206/news_1b6invitro.html • http://www.patentdocs.net/patent_docs/2008/02/invitrogen-and.html THANKS FOR LISTENING! ANY QUESTIONS?