Natural product patents case study: Cyclosporin A

Natural product patents case study: Cyclosporin A

Cyclosporin A was first isolated in 1971 from the fungus Tolypocladium inflatum. It was investigated for its anti-fungal activity, but its spectrum of activity was too narrow to be clinically useful. In 1976, its potent immunosuppressive activity was discovered and interest in the compound was renewed.

Since cyclosporin A was found to have such good immunosuppressive activity and much lower toxicity than other immunosuppressive agents available, it has been the subject of many other studies. The total synthesis of cyclosporin A was reported in 1982 and since then many derivatives of cyclosporin have been prepared and patented. However, cyclosporin A is still used worldwide as the primary immunosuppressive drug and the patent relating to cyclosporin A (US Patent No. 4,117,118 ) was a valuable asset for the drug company Sandoz Ltd (now Novatis AG).

US Patent No. 4,117,118 relates to two isolated cyclosporin compounds, including cyclosporin A, and their use as anti-arthritic agents, immunosuppressive agents, and for suppressing the rejection of transplants. The specification describes the fermentation of microorganisms, the isolation of the cyclosporin compounds from the fermentation broth and their purification. The specification also describes the molecular structure of cyclosporin and provides physical data including UV spectral data, IR spectral data, proton NMR, HRMS and microanalysis.

No derivatives or structure-activity relationships are described in the specification and the claims of US 4,117,118 are limited to the two cyclosporin compounds only by claiming the compounds by molecular structure or by physical data. Claim 1 is directed to compounds in amorphous form having specified UV, IR, NMR and mass spectral data. Claims 2 and 3 claim the compounds by molecular structure. The claims of this early patent therefore have been restricted to the natural product compounds themselves.

Lessons for patent drafting

This patent illustrates that a compound can be claimed by physical data rather than molecular structure. It is important to include claims to compounds having specific physical data to ensure that if the elucidated molecular structure is incorrect, there are claims that unambiguously define the compound that has the biological activity. Furthermore, broader protection may be obtained if structure activity relationships are elucidated and derivatives of the compounds prepared and tested.