Sandy M Thomas

DNA patenting: the end of an era?

Debates on patenting DNA must evolve to reflect the global decline in filings and regional disparities in patenting activity.

Affymetrix: genes on chips

Affymetrix has developed state-of-the-art technology to attach small oligonucleotides onto glass surfaces using methods common to the electronics industry. Such arrays of DNA (gene chips) can be used to screen for mutations in disease genes as well as for changes in viral genomic structure (e.g., HIV-1 and -2). Other companies such as Hyseq have developed similar technologies in parallel and are currently in dispute with Affymetrix over the patent position. Whatever the outcome, the use of DNA attached to glass, quartz or electronic surfaces will be the way forward in mutation detection and gene expression studies.

Merck: the scattering of DNA sequence patents

Merck has been vocal over the principle of not patenting human DNA sequences that could be considered as research tools for developing small molecule pharmaceuticals. The Company has been particularly noted for its contribution to the expressed sequence tag (EST) approach to human gene discovery and, most recently, has been active in support of industrial scale knock-out mouse generation. However, it is quite clear from the patents described here that Merck considers the patenting of gene sequences to be important, if not crucial, in various disease areas, in particular antivirals and receptor biology.

Isis Pharmaceuticals: what is the sense in antisense?

Isis Pharmaceuticals has an impressive patent portfolio built upon its ability to synthesise modified synthetic oligonucleotides in large amounts. The use of these compounds to inhibit gene expression by blocking translation or activating RNase H has been demonstrated in vitro, and one product is in Phase III clinical trials. Much depends upon the Company’s ability to use antisense oligonucleotides designed to inhibit ras, raf, ICAM-1 and protein kinase C in disease tissues where these proteins are valid drug targets. Having established this, the question of drug delivery in whole animals will need to be addressed.

Human Genome Sciences: patenting the genome

In the 18 months between July 1995 and December 1996 over 97 PCT patent applications were published on behalf of Human Genome Sciences, Inc. Such a portfolio would be impressive for a biotechnology company with an extensive history and a major capitalisation, but for a small start-up to acquire a patent portfolio equivalent to, for example, Amgen’s is quite spectacular. Patented genes and proteins range from soluble growth factors, such as fibroblast growth factor-10, to bone morphogenic protein-10 and interleukin-6. Also included are enzymes that could act as targets for chemotherapy and a substantial number of novel human gene protein coupled receptors. The remarkably broad claims range from the gene, the protein, any polymorphism through to undiscovered drugs acting on these targets, as well as the use of many of these genes in gene therapy.

Review Biologicals & Immunologicals: Intellectual property rights in biotechnology

The development of intellectual property rights for biotechnology has occurred in a series of complex and often contentious steps. By granting many of the first patents for genetically engineered organisms and biological molecules, the US has played a leading role in shaping policy worldwide. This article reviews the role of patents in the development of biotechnology and discusses the new challenges posed by the integration of genomics into the drug discovery process.

Plant DNA patents in the hands of a few.

NATURE | VOL 399 | 3 JUNE 1999 | www.nature.com 405 Sir — I am very much in favour of Nature’s use of Scientific Correspondence to bring to our attention potentially important research before full publication of results. But there is a need for scientific rigour in the presentation of the information to ensure that it is not misrepresented. The report by Losey et al. in Scientific Correspondence is a preliminary research finding offering insight into the topical and important issue of genetically modified (GM) crops (Nature 399, 214; 1999). It has alerted the UK Advisory Committee on Releases to the Environment (of which I am chairman) to a potential problem that will require very serious thought. It has also been assumed to demonstrate that GM crops harm butterflies and has fuelled public anxiety about such crops. The report is highly indicative of harm caused by pollen from the maize plants used in this particular study, but the work is at this stage preliminary rather than definitive. It is clearly stated in the text, for example, that pollen for the non-Bt (Bacillus thuringiensis) maize control was from an unrelated, untransformed hybrid. However, there is no reported control to demonstrate that pollen from the transformed variety was not toxic in the absence of the functional Bt gene. Losey et al. refer to a study (their ref. 3) stating that maize pollen is dispersed over at least 60 metres, and comment that a substantial portion of available milkweed (eaten by monarch butterflies) may be within the range of corn pollen distribution. But Losey et al. do not report a dilution study, so there is no evidence that dilute pollen would have an impact on larvae. Of course it is desirable to point out the potential harm that may arise from pollen dispersal, which in this case could be very important, but the data reported by Losey et al. do not directly pertain to this issue. On 20 May I stated on the BBC Radio Today programme that the letter by Losey et al. was not peer reviewed and that the work might be flawed. I am now aware that it was peer reviewed (as are all contributions to Scientific Correspondence), and wish to apologize. My suggestion that the work might be flawed was not intended as a slight but was a reminder to the press that preliminary observations should not be overinterpreted. Regrettably, most reporting of the communication has almost entirely ignored the need for such caution. John E. Beringer School of Biological Science, University of Bristol, Woodland Road, Bristol BS8 1UG, UK Cautionary tale on safety of GM crops

Shares in the genome

Recent initiatives in the public and private sector will bring forward completion of the human genome sequencing project. These developments have given greater emphasis to uncertainties over the implications of patents for expressed sequence tags (ESTs) and single nucleotide polymorphisms (SNPs). In the absence of firm guidance from public policy, inventors, particularly those from the private sector can be expected to file patent applications vigorously on partial and full DNA sequences. Unless the value of royalty payments for patents on partial DNA sequences is reasonably modest, the patent system risks failing the very innovation system it was established to promote.

British Biotech: how much value is there in metalloproteinase inhibitors?

The value of British Biotech is built upon two matrix metalloproteinase (MMP) inhibitors, Marimastat and Batimastat, both in clinical trials. These are supported by a strong patent portfolio in the area. A second aspect of the companys activity is in the area of platelet activating factor (PAF) antagonists. Two genetically engineered proteins, a modified plasminogen thrombolytic and an inhibitor of stem cell proliferation make up the pipeline.

The role of intellectual property in biotechnology

The fundamental importance of patenting to the successful exploitation of biotechnology is underlined by events over the past 12 months. The voting by the European Parliament in favour of a modified Directive to clarify what can and cannot be patented is to be welcomed. The legal challenge to restrict broad patents by a UK ruling on a method of producing vaccines for hepatitis B was also welcomed by many who consider that the European Patent Convention should be revised to allow patent challenges on the grounds of excessive breadth of claims. Other developments concerning the patenting of DNA reviewed in this article emphasise the uncertainty surrounding the strength of intellectual property in the genomics areas.