Monday, January 28, 2008

Patent Circle Exclusive: Tarceva Patent Litigation Analysis III

Is Erlotinib a derivative of Gefitinib?

Although Erlotinib and Gefitinib have same 4-anilinoquinazoline base structure, but significantly differs in substituents attached at quinazoline and anilino rings. In both Erlotinib and Gefitinib, quinazoline ring is unsubstituted at the 2-, 5- and 8-positions and have anilino substituent at the 4-position and a substituent attached at the 6- and 7-positions.

In Gefitinib, 6-position of quinazoline ring is substituted with 3-morpholinopropoxy and 7-position with methoxy group and anilino ring is substituted with Fluorine and Chlorine, whereas in Erlotinib 6- and 7-positions of quinazoline ring are substituted with 2-methoxy-ethoxy group and anilino ring is substituted with ethynyl radical. It is well recognized in chemistry that a derivative is a compound formed from a parent compound by replacement of one atom with another atom or group of atoms, but retaining essential elements of the parent compound, for example, Flumezapine and Olanzapine belonging to same family of thienobenzodiazepines and sharing same thienobenzodiazepine base structure.

Anyone with a reasonable understanding of organic chemistry would be able to judge that Erlotinib structurally is not a derivative of Gefitinib, even though sharing same 4-anilinoquinazoline base structure. Erlotinib differs structurally from Gefitinib, by substitution of an ethynyl radical for fluorine and chlorine atoms in Gefitinib at anilino ring and substitution of 2-methoxy-ethoxy groups for 3-morpholinopropoxy and methoxy group at the 6- and 7-positions. Then do Erlotinib need to show improved efficacy under section 3(d) of the Act over Gefitinib? According to the explanation provided therewith section 3(d), any derivative of known substance to be patentable under the Act need to differ significantly in properties with regard to efficacy. Considering that Erlotinib is structurally not a derivative of Gefitinib, triggering section 3(d) efficacy requirement will absolutely be excessive.

Does derivative include structural analogues? To be continue…

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