Schinopharm failed to revoke the process patent on Gemcitabine

In a Judgement by Hon'ble Judge MR. JUSTICE KITCHIN on the revocation case of EP (UK) No 0,577,303 ("the Patent") which is owned by Eli Lilly & Company, the Judge held that the "The allegations of obviousness and insufficiency have not been made out. The Patent is valid and the action must be dismissed".

The Patent has an earliest priority date of 22 June 1992 and relates to a new process for making a compound called gemcitabine, which is a drug used for the treatment of cancer and sold by Lilly under the name GEMZAR. It is of considerable commercial significance with worldwide sales in 2007 of about US $ 1.36 billion.

Gemcitabine is a nucleoside analogue. Nucleosides themselves are the building blocks of DNA and RNA and are composed of a sugar component linked to a nucleobase component by a glycosidic linkage. Gemcitabine has a very similar structure to a nucleoside called deoxycytidine.

The validity of patent was challenged on the basis of obviousness and insufficiency of disclosure grounds.

Prior Arts:


The obviousness allegation relies upon the following eight prior publications:
i) United States Patent 4,526,988 ("Hertel 1");
ii) European Patent 0,122,707 ("Hertel 2");
iii) A paper entitled "Synthesis of 2-Deoxy-2,2-difluro-D-ribose and 2-Deoxy-2,2-difluoro-D-ribofuranosyl Nucleosides" by L. W. Hertel et al (Journal Organic Chemistry, 1988) ("Hertel 3");
iv) A paper entitled "Stereospecific Synthesis of 2-Deoxy-2,2-difluororibonolactone and Its Use in the Preparation of 2'-Deoxy-2',2'-difluoro-ß-D-ribofuranosyl Pyrimidine Nucleosides: The Key Role of Selective Crystallization" by T. S. Chou et al (Synthesis, 1992) ("Chou");
v) A paper entitled "An Investigation by H NMR spectroscopy into the factors determining the ß:a ratio of the product in 2'-deoxynucleoside synthesis" by A.J Hubbard et al (Nucleic Acids Research, 1984) ("Hubbard");
vi) A paper entitled "The Synthesis of 2'-Deoxy-5- Trifluoromethyluridine Utilizing a Coupling Reaction" by H. Kawakami et al (Heterocycles, 1990) ("Kawakami");
vii) European Patent Application 0,428,109 ("Vemishetti");
viii) A paper entitled "Antiviral Nucleosides. A Stereospecific, Total Synthesis of 2'-Fluoro-2'-deoxy-ß-D-arabinofuranosyl Nucleosides" (Journal Organic Chemistry, 1988) by H.G. Howell et al ("Howell").

The attack was founded primarily upon Chou, which explicity refers to Hertel 3.

Findings on Obviousness:
I can take all these publications together. Once again, the allegation of obviousness is not founded on any one of these papers as such. Rather, it is said that the invention of the Patent was obvious in the light of these papers when read with Hertel and Chou. However, there was no evidence or attempt to prove that a skilled person would have found any of these papers in the light of his common general knowledge or on a reading of Hertel and Chou. In my judgment it is not permissible to present to an expert different items of prior art which are not said to be common general knowledge and ask him whether it would have been obvious to read them together. It may well be the case that the skilled person, presented with Hertel and Chou, would not have considered it necessary to supplement his common general knowledge and, even if he did, he may never have found these further publications. I therefore reject the submission it is permissible to read them, individually or collectively, together with Hertel or Chou. The allegation of obviousness based on these publications fails at the outset.

Findings on Insufficiency: The question then is whether the claim is enabled across its width. Here I have some sympathy with Scinopharm in that the claims certainly do not identify all those process steps which are necessary to achieve that result and, as I have indicated, both sides contend that having at least a molar equivalent of nucleobase is not itself a sufficient condition. However, Professor Boons has explained in his unchallenged evidence that the Patent provides a large number of examples and the skilled person would be able to identify the general conditions which would enable him to work the invention and he would certainly have been able to follow the teaching to produce a ß enriched product, and gemcitabine in particular. The allegation of insufficiency therefore fails on the evidence.

The whole judgement can be read here.