Dominant patents on antibiotic resistance genes

Comparison between patents on antibiotic resistance genes in general, nptII and hygromycin

Are there dominant patents in this field?

One can say, yes, in the United States there are dominant patents on the use of antibiotic resistance genes for the selection of transformed plants. That means, it is likely that any other patented invention on this subject matter or any user of antibiotic resistance genes would not have freedom to operate unless permission is granted for the use of the dominant inventions.

The dominant patents on this field are owned by Monsanto and cover a chimeric gene having any antibiotic resistance gene (see analysis in Antibiotic resistance genes in general). The patents differ with respect to the type of promoter used to control the antibiotic resistance gene as follows:

Type of promoter
US 6174724 anypromoter naturally expressed in plants
US 6255560 (lapsed in 2005)
CaMV 35S and 19S
US 5034322 opine synthase and rbcS

Of these, the first one, US 6174724, is the broadest. As discussed in Antibiotic resistance genes in general any promoter that expresses naturally in plants may include any promoter derived from any plant gene and also from genes whose expression only occurs in a plant cell. As long as any of the sorts of promoters claimed in these patents is used in a chimeric gene with any antibiotic resistance gene, the construct will be likely covered by the claims.

It means that nptII and hpt genes and even other antibiotic resistance genes not analysed in this paper, such as bleomycin resistance gene conferring resistance to bleomycin and phleomycin and genes conferring resistance to gentamycin and streptomycin, could be covered by the claims of this patent, if they are part of a chimeric gene having the patented elements.

What are the limits?

The limits to the breadth of the patents are mainly

  • In the promoters
    If you think of any other promoter that does not fall within any of the claimed groups, a devised chimeric gene might be outside of the claims.
  • In the country where the patents are issued
    These broad patents are only in force in the United States. Patents with such broad scope have not been granted in any other country. Therefore, Monsanto can be only enforce its patent rights over the inventions in the United States.

You may ask whether the use of these patented chimeric genes in a non-plant organism (e.g., animal cell) would be non-infringing? Remember though that patent rights allow the owner to exclude others from “making, using, selling, or offering to sell”. Because these patents are protecting products, not processes, the sort of use of a protected product is irrelevant. As long as you have made or used (or sell or offer to sell) a product that comprises the elements of the claimed chimeric genes, you would be infringing.

In what way are the patents on nptII and hpt genes dominated by this trio of patents?

This question is limited to the United States as the dominant patents are only granted and in force in this country.

  • nptII patents
  • Monsanto is also the owner of patents on the use of nptII as antibiotic resistance gene for plant transformation (see IP aspects of the npt gene ). Therefore, Monsanto is in an advantageous position by having the patent rights on any antibiotic resistance gene as well as on a gene encoding a neomycin phosphotransferase enzyme. In the latter patent, it means that apart from the nptII gene, other genes coding for a neomycin phosphotransferase, i.e. nptI, could be encompassed by the patent claims.The bifunctional marker by the National Research Council of Canada has the nptII gene linked to a gus gene and is not limited to particular organisms. It might appear that the fusion gene is outside the scope of the Monsanto patents. However, if the construct having the fusion gene comprised the elements claimed in the Monsanto patents, then, despite having in addition the gus gene, the construct might infringe the protected Monsanto’s chimeric genes. The transition word “comprising” used in the Monsanto’s claims means that the claimed chimeric genes contain all the elements listed but can also include additional elements. Therefore, having a chimeric gene with all the claimed elements plus the gus gene does not avoid infringement.

    The aminoglycoside phosphotransferase gene claimed by Cetus Corporation might fall under Monsanto’s patents, if the expression vector containing the modified truncated aphI gene, which is an antibiotic resistance gene, encompassed any of the promoters claimed by Monsanto controlling the gene and a poly(A) signal. Furthermore, such expression vector might only be infringing if it was capable of being used for plants. Other eukaryotic organisms are not covered by the Monsanto’s claims.

  • hpt patents
  • Despite the solid patent portfolio now owned by Syngenta on cloning vectors containing the hpt gene (see IP aspects of the hpt gene), the claimed constructs for plant transformation, in particular, appear to be encompassed by Monsanto‘s protected chimeric genes. Once more, this situation is only applicable to the United States patents, which are assigned to Syngenta.The United States hpt patents that are members of families 1 and 2 encompass more than plants, including prokaryotic and eukaryotic organisms. The recombinant DNA cloning vectors of the United States patent of family No. 1 would have to contain a eukaryotic promoter falling within one of the types of promoters claimed by the Monsanto patents to be encompassed by the Monsanto patents. The claimed plasmids of the United States patent of the family No. 2 contain promoters that are either derived from yeast genes or from eukaryotic genes which are not naturally expressed in plants. Therefore, these plasmids are not likely claimed by these Monsanto patents.

    In contrast, the chimeric genes claimed in the two United States Novartis patents of family No. 3 are more likely to be dominated by the Monsanto patents on antibiotic resistance genes in general. The Novartis chimeric genes confer plants resistance to the hygromycin antibiotic.

    These chimeric constructs comprise a plant-expressible promoter and a terminal signal sequence apart from the hygromycin resistance coding region. These are akin to the constructs claimed by Monsanto, but if the promoter and the terminal signal sequences are not the same as the ones claimed by Monsanto, the chimeric genes could not be encompassed by the Monsanto’s constructs.