A. Cipla v. Roche in the post-grant opposition against Patent No: 208718
(i) File Wrapper details:
(a) Patent Application Number: IN/PCT/2001/0484/CHE
(b) Date of filing patent application: 03-04-2001
(c) Date of publication under Section 11(A): 04-03-2005
(d) Date of publication of granted patent under Section 43(2): 31-08-2007
(e) Date of filing post-grant opposition: 01-09-2008
(f) Date of hearing: 6th July, 2010
(g) Date of judgment: 26th August, 2010
(h) Title of invention: Pharmaceutical composition in solid unit dosage form.
Counsels for the Patentee: M/s DePenning and DePenning instructed by Ms. Sujatha Subramanian, In-House Counsel for Hoffmann La Roche AG.
Counsels for the Opponent: Majumdar & Co. Instructed by Ms. Girish Bhawmani, In-House Counsel of Cipla Ltd.
(ii) About the invention: The aim of the invention as described in the specification “is to ensure that the forms of administration travel through the stomach and the active principle is released only in the intestinal tract.” Pharmaceutical forms of the claimed composition are used primarily to treat calcium metabolism diseases such as osteoporosis and tumour osteolysis resulting from bone metastases.
The main claim of the patent is as follows “1. A pharmaceutical composition in solid unit dosage form, said dosage form comprising an inner phase containing as the active substance diphosphonic acid or a physiologically compatible salt thereof, said active substance being present in the dosage form in an amount of from 0.25 to 100 mg, and an outer phase containing stearic acid in an amount of less than 5% by weight of the dosage form.” Claims 2 to 9 are dependent on Claim 1, while the remaining claims are process claims. This main claim was amended, by Roche itself, during the course of the post-grant opposition, to replace diphosphonic acid with ibandronic acid as the active substance. The amendment was most probably moved to get around the prior-art cited by Cipla during the course of the opposition.
(iii) The Issues and Decision in the Post-Grant Opposition: The decision of the Asst. Controller K.S. Hariram in this case is very well-structured, so much so that it has better form than some of the High Court judgments that I’ve come across. He presents arguments from both the opponent and the patentee, followed by the recommendations of the Opposition Board and concludes with his reasons for either supporting or disagreeing with the Opposition Board and the parties. While the analysis is rigorous in certain portions, when compared to other Opposition decisions, there was still plenty of scope for it to be more lucid.
(A) The Main Issues:
(i) Lack of Inventive Step: The inventive step, of this patent, lies in the determination of the correct proportion of the active substance (ibandronic acid or a physiologically compatible salt) vis-a-vis the lubricant (stearic acid), in order to ensure the release of the active ingredient at the right location in the body. In the case of the present patent the claimed formulation ensured the release of the active substance, after 30 minutes, in the intestinal tract. An early release, that is before the drug reaches the intestinal tract can have adverse effects on the human body. A late release may reduce the potency of the drug. The formulation also displayed greater thermodynamic stability at temperatures over 40 degree centigrade with ‘no noticeable differences from the original rate of release’. The inventive step in the process claims related to greater manufacturing ease with lesser wastage of material.
The Opponent sought to establish the lack of an inventive step on the basis of the following prior art documents:
(a) Ex-1: US 4859472:
(b) Ex-2: Remington; the Science and Practice of Pharmacy;
(c) Ex-3: WO93/21907
On the basis of these prior-art documents, which were supported by an expert witness, Cipla sought to argue the following:
(a) The use of the lubricant in the proportion claimed by the patentee i.e. 5% of the dosage, was taught in Ex-1 and that although the lubricant may have been different it would have motivated a person skilled in the art to test other lubricants in the same proportion.
(b) The use of the lubricants in general on the outer phase was taught by Ex-2. In particular this prior art taught the use of magnesium stearate and stearic acid as lubricants.
(c) The replacement of magnesium stearate with stearic acid was taught by Ex–3 thereby providing a motivation to a person skilled in the art to replicate this in other inventions.
It was argued that on a combined reading of the above cited prior art it was obvious to a person skilled in the art to formulate the active substance with the lubricant, stearic acid, in the proportion claimed by the patentee.
The Opposition Board accepted the Opponent’s argument and stated that a person skilled in the art would have been motivated by the prior art to use stearic acid as a lubricant in the claimed proportion i.e less than 5% of the dosage weight.
The Controller however disagreed with the Opposition Board and the Opponent and instead accepted Roche’s arguments that the composition claimed was inventive in light of the cited prior art which incidentally had already been discussed by Roche in the main body of its specification. He arrives at this conclusion on the basis of a ‘problem-solution’ approach wherein he first identifies the problem that is sought to be solved by the claimed invention. In this regard he finds that the claimed dosage solves the problems in prior art since it acheives better rates of dissolution than what existed in the prior art and also that the claimed dosage demonstrated greater thermodynamic stability. The weight of the active substance in the prior art was much higher than what was claimed in the current invention. The Controller then adequately distinguished each piece of prior art cited by the Opponent.
In regards Ex-1 the Controller stated that it in fact taught away from using ibandronate and stearic acid in the dosage. Moreover the Controller points out that while Ex-1 suggests the use of multiple lubricants the claimed invention uses only one lubricant. In regards Ex-2 the Controller stated it taught the wide-spread use of magnesium stearate as lubricants, although its hydrophobic properties can retard distintegration and dissolution, thereby suggesting that it was not the best lubricant. The Controller further stated that although Ex-2 discussed the use of several other lubricants it did not specifically motivate or suggest to a person skilled in the art to use stearic acid as a substitute for magnesium stearate. In regards Ex-3 the Controller clearly stated that this document discussed the use of multiple lubricants instead of one single lubricant as was claimed by the patentee and that there was nothing in this document to suggest the use of only stearic acid as a lubricant.
In conclusion while holding the claims as inventive, the Controller cited U.S. and EPO case law to state that a “chemical process is not obvious to try simply because it can be performed without difficulty but only if it can be shown by reference to the state of the art that the process concerned could be fairly expected to produce the desired results, or, in other words, to solve an existing technical problem”.
(ii) Prior public use/public knowledge: This ground of opposition seeks to establish that the invention was anticipated by prior use and working within India, before the priority date of the patent application. Both the Opposition Board and the Controller dismissed this argument of Cipla’s out of hand since it was not substantiated with any evidence.
(iii) Not an ‘invention’: Section 25(2)(f) of the Patent Act, 1970 allows an opponent to oppose a patent on the ground that the subject of any claim of the complete specification is not an invention within the meaning of the Act.
Under the scheme of the Patent Act prior to the 2005 amendments, an invention was defined solely under Section 3 of the Patent Act. However the Amendments in 2005 sought to define the term invention within the definition section i.e. Section 2(1)(j) thereby allowing for two sections to define the scope of an ‘invention’.
The scope of an opposition in Section 25(2)(f) should have ideally been limited to a challenge on the basis of Section 3 since arguing this ground on the basis of the definition of an ‘invention’ in Section 2(1)(j) would have been futile because this definition is based on the concept of an ‘inventive step’ which was argued as a separate ground of opposition in this case.
Instead of confining the scope of Section 25(2)(f) to Section 3, Cipla tried to first argue Section 25(2)(f) on the ground that the claimed invention was not an ‘invention’ in terms of Section 2(1)(j), after which it sought to argue Section 3 as a separate ground. While the opposition board was silent on this argument the Controller, rightly, dismissed this argument on the grounds that the patentee had already proved that the claimed invention was a result of an inventive step. Therefore an argument that it was not an invention within the terms of Section 2(1)(j) was simply repetitive in this case.
(iv) Unpatentable subject matter: Under this ground of opposition Cipla attempted to establish that the patent claimed subject mattet which was not patentable under Section 3(d) and Section 3(e) of the Patent Act.
(a) Section 3(d): Section 3(d) was not used in its regular “efficacious” context since Cipla only argued that the process claims (i.e. 10, 11 & 12) did not involve any new step and that it does not result in a new composition having regards to the prior art. The latter, relatively unkown portion of Section 3(d) states that the following shall not be an invention: “the mere new use of a known process, machine or appartus unless such known process results in a new product or employs at least one new reactant”. The Controller however agreed with the patentee’s contention that Section 3(d) was inapplicable in this regard since the process resulted in a new composition containing ibandronate and less than 5% stearic acid.
(b) Section 3(e): Cipla then attempted to oppose the patent on the basis of Section 3(e) which states that the mere admixture of two known substances, which merely results in the aggregation of the individual properties of the two substances, is not an invention. In order to surmount the Section 3(e) barrier a patentee is required to prove that the combination of the known substances has resulted in a syngerism wherein the combination displays properties that are not displayed individually by each component. In the context of the present case Cipla sought to argue that the claimed invention demonstrated only the individual properties of its components. The decision however then proceeds to state that Cipla, in its written submissions filed after its oral arguments, argued that the use of 5% stearic acid with ibandornate can be contemplated in view of the prior art teachings and that the same doed not provide any unexpected findings in the view of the same. Therefore instead of limiting arguments to a lack of synergy, Cipla seems to have argued that the syngery was obvious in light of prior art. The patentee opposed this on the grounds that the same was not pleaded in the main opposition and that the subsequent written submissions can not be expanded beyond the scope of the initial opposition. In any case the patentee argued that the syngery was non-obvious. The patentee also stated that the syngeristic properties had been adequately established with the help of three examples in the specification.
The opposition board in its decision agreed with Cipla’s argument that syngerism had not been adequately established in light of the prior art cited by Cipla. In my opinion this was a wrong analysis because the requirement of syngerism under Section 3(e) is a requirement that has to be proved in absolute terms and not in degrees of relativity. If it was required to be argued in the context of prior art, then the argument is essentially one indicating a lack of an inventive step. The analysis should have merely proceeded on the indivudal properties of the components as they exist in isolation from any other components.
The Controller disagreed with the Opposition Board on the grounds that the prior art compared by the opponent was not relevant since it discussed different substances from what had been claimed in the patent. The Controller instead agreed with the Patentee that the three examples described in the specification adequately establish the synergistic effect of the claimed invention.
The Section 3(e) challenge was thus dismissed.
(v) Insufficiency of description: The Opponent, Cipla, argued that the patentee had failed to sufficiently describe the invention or the method by which it is to be performed. In specific it objected to the lack of comparative data of alleged unexpected results with regards to the entire group as claimed in the patent. The Patentee rebutted this by pointing out to examples within the specification which adequately described the workings of the invention. The Opposition Board agreed with the opponent and provided a list of alleged deficiencies in the description of the invention in the specification. The Controller however dismissed this ground because the Opponent had merely made a statement without providing any specifics. In which case, it begs the question as to why the Opposition Board is seeking to provide, suo moto, a list of deficiencies. Should the Opposition Board be allowed to go beyond the scope of the pleadings?
(vi) Breach of Section 8: The Opponent attempted to challenge the patent on the basis of the Delhi High Court’s interpretation of Section 8 in the case of Chemtura Corporation v. Union of India. Cipla’s counsel Mr. S. Majumdar had deployed Section 8 to a lethal effect in the Chemtura case. In the present case Cipla tried to argue that Roche had failed to submit all necessary information of corresponding patents in foreign countries, including the prosecution history of the U.S. patent. In doing so however Cipla failed to actually lead as evidence,, the documents which were allegedly suppressed, before the Indian Patent Office. In regards the Section 8 argument both the Opposition Board and the Controller rejected Cipla’s argument on the grounds that Roche had fulfilled all its Section 8 requirements. In particular it pointed out that since the corresponding US Patent itself had been filed there was no need to file the entire prosecution history of the same.
(B) Other Issues: