Cipla’s Patent Application For HIV Drug rejected

The Indian Patent Office rejected Cipla’s patent application for its HIV drug composition comprising combination of “ritonavir” and “darunavir”. The application, in particular, was directed to a pharmaceutical composition comprising a solid unit dosage form comprising: (i) ritonavir; (ii) darunavir; (iii) a water insoluble polymer and/or water soluble polymer, wherein the ratio of the weight of the ritonavir or darunavir to the weight of the polymer is from 1:1 to 1:6. Further, the claimed composition was a tablet composition comprising ritonavir and polymer in first layer and darunavir in second layer. The first layer is obtainable by hot melt extruding, and the second layer is obtainable by direct compression or by wet granulation.

The application was rejected on the grounds of lack of inventive step in view of the prior published documents. The controller cited 6 prior art documents and heavily relied on one particular D6: US 2005/0048112 in his inventive step analysis which describes that solid pharmaceutical dosage forms comprising ritonavir and, a second species of HIV protease inhibitor, including TMC-114 (darunavir). Therefore, according to the Controller, D6 provides strong motivation to formulate a solid pharmaceutical dosage form that comprises both ritonavir and darunavir. D6 additionally discloses that dosage may be provided as dosage forms consisting of several layers and such “multilayer forms have the advantage of processing  two active ingredients which are incompatible with one another  or controlling the release characteristics of the active ingredient(s). The claims were therefore considered obvious by the Controller. in addition to this, the Controller held that the claimed subject matter does not clearly show advantage/surprising effect over prior art composition to show non-obviousness (no comparative data being provided by the Applicant).

The Controller also rejected the application under section 3(d) as he considered the  new layered form of a known combination of prior art, as being statutorily barred from the patentability u/s 3 (d).


Second generation Tygacil granted a Patent

The Indian Patent Office issued its order dismissing two pregrant oppositions filed by NATCO and Lupin against Wyeth for their commercial product, Tygacil.

The application claims a composition comprising: (a) tigecycline; (b) a carbohydrate chosen from lactose, mannose, sucrose and glucose; and  (c) and an acid or buffer, the molar ratio of tigecycline to the said carbohydrate is between about 1:0.2 to about 1:5 and the pH of the composition is between 3.0 and 7.0.

The Controller opined that the application claims a second generation formulation with selective carbohydrate at a low pH with tigecycline. Experimental results in the specification point to epimerization of tigecycline in presence or absence of lactose and also show that in presence of lactose, the epimerization of tigecycline is less and therefore tigecycline is stabler.

The Controller therefore held that the formulation of the instant invention is not a mere admixture but shows synergism /surprising result and therefore cannot be held under section 3(e) of the Act . The results are not predictive from prior art and hence it is inventive too.

The Controller also held that the composition claim does not attract section 3(d) and in this regard relied on the decision of the IPAB in Allergan Inc. Vs. Ajanta. section 3(d) of the Act considers the following not Patentable: –

“(d) the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known substance or of the mere use of a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant.

Explanation.—For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy;”.

The Controller held that the combination mentioned in the explanation of section 3(d) can only mean a combination of two or more of the derivatives mentioned in the Explanation or combination of one or more of the derivatives with a known substance which may result in a significant difference in efficacy. The claimed composition of the instant invention cannot be stated to be a new form of a known substance and therefore does not attract section 3(d).

The order also discussed legal issues, and in particular discussed if a delay of 28 days to file the reply statement and evidence when considering rule 55(4) of the Patent rules should be condoned. The Controller held that the applicant desired to contest the opposition to safeguard their rights (they timely filed a petition for extension of time and correction of irregularity) and for only a little late in filing the reply statement and evidence, and it would not be proper to debar them to contest on this highly technical issues and that will be against the natural justice.