EP 257542

The European patent EP 257542 protects the use of a specific strain of Streptomyces viridochromogenes.

Widely protected in many jurisdictions, the independent claim of this patent recites a bar gene from a specific Streptomyces viridochromogenes strain, DSM 4112. Dependent claims recite the use of the bar gene from strain DSM 4112 as a selectable marker for genetically modified bacterial and plant cells. The use of the bar gene as a selectable marker in bacteria (not mentioned in the claims of the “Dominant bar gene patents” belonging to Plant Genetic Systems (PGS)) is restricted here to the bar gene as described in Claim 1.

Any phosphinothricin-resistant plants that contain the described bar gene are also protected (Claim 8).

Claim 7 recites another use of the bar gene isolated from S. viridochromogenes not present in the claims of the dominant patents, namely to acetylate L-phosphinothricin. This acetylated compound is of commercial interest in another field of application, the selective destruction of tissues expressing the deacetylase gene, e.g. for the production of male sterile plants when the gene is expressed in the pollen sac.

EP 275957

European patent 275957 protects the same gene as the previous patent. However it is codon-optimized for expression in plant cells.

Due to differences in codon usage, bacterial genes are not always expressed well in eukaryotic cells. These differences are a consequence of divergent evolution of the protein-synthesizing machinery. As we learn more from genomic sequence analysis of many species, we can infer which codons work best for different plant families. Most variation is found in the last base of the triplet that codes for an amino acid (wobble hypothesis). The wobble can also account for differences between the average GC content of plant versus bacterial genes.

Claim 1 recites in general terms an adaptation of the genetic code to that of plants. This exploits the flexibility provided by the redundancy of the genetic code (wobble) and it also allows consideration of other relevant issues in gene design, e.g. the elimination of repetitive or palindromic sequences that might interfere with gene expression.

An example of an optimized sequence is provided in dependent Claim 2. Plant cells harboring the transgene are protected (Claim 8) but so too are host cells, typically bacteria, used to manipulate the intermediate and used during the transformation process.

The remaining patents in the Hoechst AG assigned family are derived from the same German patent applications that gave rise to European patent EP 257542 B1. The earliest priority date is 23 Aug 1986, which corresponds to German application DE 3628747. The following four U.S. patents are all related to each other by continuation and division procedures. Divisional applications arise from when the claimed subject matter covers multiple inventions according to U.S. Patent Office Standards.

US 5273894

Claims in this patent are essentially the same as those described in European patent EP 257542 B1, namely a bar gene isolated from Streptomyces viridochromogenes strain DSM 4112. Other claims recite plant and bacterial cells transformed with the gene.

Claim 10 recites the use of the bar gene as a tool to acetylate L-phosphinothricin, similar to Claim 7 in European patent EP 257542 B1.

US 5276268

Claims in this patent are similar to those in European patent EP 275957 B1. Claim 1 refers to a bar gene modified to reflect plant codon usage to enhance gene expression. Modifications are based on the flexibility conferred by the redundancy of the genetic code. Other allowed claims recite plant and bacterial cells expressing the introduced gene (Claims 5-11) as well as a process to generate plants resistant to the herbicide phosphinothricin (Claims 12-14).

US 5637489

Claim 1 recites a process to obtain a phosphinothricin-resistant plant by incorporating a bar gene isolated from Streptomyces viridochromogenes strain DSM 4112 into the plant genome. Claim 4 recites a plant containing such a gene.

Claim 3 states that the sequence should contain at least nucleotides 258-806 of the given sequence, which corresponds exactly to the structural gene.

US 5879903

United States patent 5879903 recites methods of using the bar gene isolated from Streptomyces viridochromogenes strain DSM 4112 to select for transgenic bacterial and plant cells respectively.

Again, the patent does not protect bar genes isolated from other bacterial species or genera. Use of the bar gene as a selectable marker in bacteria is not mentioned in the claims of the dominant bar gene patent family — issued to PGS – where the gene is mainly used to confer herbicide resistance to transgenic plants in the field. The present patent falls within the scope of the dominant patent family because the granted main claims in those patents are written in broad terms.