Part II: IPAB revokes Allergan's patent on eye drugs Ganfort and Combigan

Patent II [ORA/21/2011/PT/KOL]

The  application was filed against  patent No.219504 “Combination of Brimonidine and Timolol” for topical Opthalmic use. The combination is commercially marketed as "Combigan." The revocation was sought for on various grounds viz., that the Patent was obtained on a false suggestion or representation, that it was obvious, that it did not sufficiently disclose and violated Section 8 of the Patents Act, 1970. The patent was successfully revoked. 

Applicant

According to the applicant, the only advantage of the ophthalmic pharmaceutical composition of the impugned patent is that the patient is exposed to lesser amount of benzalkoniuim chloride (preservative) (BAK) during daily treatment regimen.  Prior art suggested that a combination of brimonidine and timolol may have potential in the treatment of glaucoma. The only difference between the impugned patent and prior art was the combination in a single composition and combination as individual composition.   Therefore the mere fact that Brimonidine and Timolol were administered in a single installation was not indicative any inventive step. Also, it was obvious that the amount of BAK required for a combination in a single composition would be less than that required in when the two drugs are administered separately. 

Furthermore, the complete specification of the impugned patent merely disclosed the constituents of the composition and not about the prior art that lead to the proposed composition.  The invention was a mere admixture the benefit provided by the invention is additive where each of the two drugs caused the respective therapeutic effect independent of each other. The advantages of combination of two drugs were known in the state of the art.

According to the applicant, the invention was not patentable under S. 3 (d) either. There was no data in the specification to show that the invention had an enhanced efficacy. The applicant submitted that S. 3(d) included “combination” and that the respondent had only shown the advantageous effect of combination of the two active ingredients over the individual active ingredients.The respondent ought to have shown the advantages of the single composition over the serial administration of the two drugs. 

Further, the respondent also failed to disclose to the controller the information required by Section 8 of the Act, in particular, the European counterpart of the subject Patent- which was not granted by the EPO.

The applicant also cited the US  Court of Appeals judgment in respect of the US counterpart of the impugned patent Allergan Inc vs. Sandoz where the patent was invalidated:

"There is extensive evidence in the prior art showing the concomitant administration of brimonidine and timolor multiple times per day, that the combination had benefits over the administration of either alone, and that there was a motivation to combine the two achieve better patient compliance."

Respondents 

The Respondents contended that the combination of two drugs in a fixed combination was neither taught nor

suggested by the prior art. This combination was purely the result of an inventive step. Serial administration and combination were two different modes of administration. The most common form of treatment was serial or concomitant administration of two or more different medications provided in two or more separate bottles. According to the respondent the teachings and prior art were against such combination. Thus, the respondent overcame these challenges which would have discouraged the person skilled in the art from trying the invention combination. Further, BAK was known to be toxic to cells. Therefore the ingredients in the uptake were not desirable.  The combination reduced side effects, was more effective than its components and was approved by the FDA. The counsel pleaded dismissal of the revocation application for applicant's lack of evidence and failure to discharge the burden of proof. Also, according to the respondents S.8 (2) spoke of processing of the application in a country outside India and it meant that the patentee’s compliance was complete if one foreign application was filed. The Patentee could not be asked to furnish details regarding the proceedings in all countries, contrary to the statute.

Decision 

The Board examined the Canadian, US and EPO judgments on challenges of the same patent.

It held that there was definitely a reasonable expectation of success, and thus the invention was obvious. The Board stressed on the importance of adducing evidence in pharmaceutical patent revocation cases, and that it is not always sufficient to rest on prior arts. In this case the history of the state of the art showed that the two drugs were popular, and that the two drugs were combined serially, and that the serial administration showed advantages over single therapy, and that Brimonidine BID was not unknown and in fact except for USA Brimonidine was given BID elsewhere, and that composition of two drugs in one bottle was known, and the claimed preservative (it was optionally claimed in fact in Claim 3) was used, and so the invention was obvious. This may not be so clear in other cases.  Also, the respondent failed to show enhanced efficacy of 'Intra ocular pressure' lowering effect of the invention compared to the serial application of Brimonidine and Timolol. It was held that in view of non-compliance of S.8 and obviousness of the patent, it was not necessary for the Board to even delve into the issue of S. 3(e). 

The Board came down heavily on the patentee for non-compliance of S. 8 and reiterated the necessary aspects for fulfilment of S.8: 

• It must be pleaded and proved that the lapse was with regarding applications in respect of the same or substantially the same invention
• The documents to prove this must be filed at the earliest if they are filed belatedly , costs may be imposed.
• The law does not say that the failure to furnish the S.8 details must be deliberate and willful or that the failure must be in regard to material particulars.
• It has been introduced to facilitate examinations and therefore the patentee must be candid and fair.
• The Controller cannot deal with this ground casually. They must adhere to the law nor can they dilute it. 
• The Patentee has a statutory duty under S.8, he cannot say that the particulars are available on the website. Nor can the Examiner condone the non-disclosure by saying the details are on the website.
• It is not a penal provision and the object of the law is clear disclosure and there can be no dilution.
• Rule 12(3) is part of the statute and indicates why this provision has been introduced and reflects the sentiments of the Ayyangar Committee report.
• The article “a” in the law cannot be understood to mean only one. Once the S.8(1) detailed particulars are given, the Controller may ask for the details relating to ‘a’ country. This means any. The Controller May ask for the Rule 12(3) details regarding any application.

More interestingly, the Board remarked: 

"It is no response to say that standard must be more lax today because information is available on the internet. It is no defence to say that if the patent is valid otherwise then discretion should be exercised in the respondent‘s favour. In any event it has been brought to our knowledge that EPO has rejected the patent and it has become final. On appeal USA has also rejected the patent. So it is not as if the respondent held an infallible patent. Above all, it is clear that the respondent withheld information that ought to have been furnished under Section 8. The patent deserves to be revoked on this ground alone."

The patent was revoked. No order was made regarding costs.