GSK’s patent on lapatinib ditosylate revoked by IPAB

GSK’s granted patent IN221171 (‘171) on lapatinib ditosylate (marketed as Tykerb), a tyrosine kinase inhibitor for treating breast cancer, was revoked by IPAB by its order of 27th July, 2013. A revocation application was filed by Fresenius Kabi Oncology Limited. The patent is revoked on ground of non-compliance with S.3d alone on basis of no proof of enhanced therapeutic efficacy vis-a-vis lapatinib di-HCl salt (known compound). Still IPAB discusses the grounds of obviousness and non-compliance with S.8 in detail as it considers these grounds important. Section 3d IPAB very straight forwardly failed the test of section 3d for the ‘171 patent. Taking precedent of Novartis Glivec case, it was held that there was no enhancement in therapeutic efficacy of the ditosylate salt as compared to the di-HCl salt and thus “”. The only enhancement w.r.t the di-HCl salts was the increase in moisture absorption property and the increase in stability which are physico-chemical properties. Next IPAB discussed the grounds of obviousness and Section 8, though it considers that non-compliance with Section 3d itself revokes the patent. Obviousness GSK’s basic patent (IN221017) on lapatinib was cited as prior art (D1) in view of three other prior art documents D2 to D4. It was argued that D1 describes a list of acid addition salts which exemplify 19 acid addition salts among which p-toluene sulphonic acid salts were one of them and even one Example 29 is a tosylate salt. It was held that at the time of invention of ‘171 patent, the inventors knew that the HCl salts of lapatinib were hygroscopic and thus having stability issues (described in background section of the ‘171 patent). D3 and D4 are non-patent basic literature articles describing selection of salts and pharmaceutical salts respectively. D2 is a prior patent WO 98/25920 disclosing tosylate salts of 3-pyridoxyl alkylene azetidine-2-yl compound and that these are less hygroscopic, more crystalline, more stable, have a higher melting point and are readily purifiable as compared to hydrochloride salts. It was argued that D3 discloses that aryl groups are said to minimize hygroscopicity as opposed to the poorly stable hydrochloride and sulphate salts which teaches towards tosylate or ditosylate salt with reasonable expectation of success in combination with D1, D2 and D4. D2 further teaches tosylate salts to sorb less moisture, are more stable and crystalline. IPAB clarified that the skilled person in obviousness analysis in Indian law is the person skilled in the art (Ms. SITA) rather than the person having ordinary skill in the art (PHOSITA) as used in US law, in reply to the Respondent’s citing of US case laws and description of skilled person as PHOSITA. IPAB held that the skilled person (Ms. SITA) would know at the time of the invention of the problem of the hygroscopicity and stability of HCl salts and it would be obvious to try for her to select ditosylate salt as taught by D1 in view of D2 to D4. IPAB further held that whether D2 belonged to another class of compounds (read analgesics) would be immaterial. IPAB asserts that:                                                                               Ex D = D3, Ex C = D2 and Ex B = D1 IPAB finally held that if the salt selection were to be made from a vast variety of salts by testing each compound with no clue available, then selection of one particular salt is not easy but in this case the clue is provided by D2 to D4 which makes the invention obvious. Section 8 IPAB rejects the ground of Section 8 in the absence of pleading and proof of violation. IPAB stated that: On another note, IPAB stressed the importance of compliance with S. 8 in a number of ways as shown below. In the opening sentence under the S. 8 heading itself, IPAB states that “”. Further excerpts of IPAB are as below: “ “ Fresenius Kabi also filed revocation petition against GSK’s basic patent IN 221017 claiming Markush structure encompassing lapatinib and pharmaceutically acceptable salts (discussed as D1 hereinabove) on grounds of obviousness, non-compliance with S.3d and S.8. This revocation petition however was dismissed by IPAB. We would discuss this in detail in an upcoming article. About the Author: Ms. Meenakshi Khurana, Patent Attorney at Khurana & Khurana and can be reached at: Meenakshi@khuranaandkhurana.com Follow us on Twitter: @KnKIPLaw.