Growing movement opposing granting of drug patents

Many more cases are being filed in India by groups representing HIV/AIDS patients against the granting of patents for HIV/AIDS medicines, adding to the initial two cases after a 2005 amendment to the Indian patent law.

Four new cases of pre-grant opposition to the patenting of the HIV/AIDS medicines have been filed by Indian groups of people living with HIV/AIDS at three separate patent offices in India.

These new cases follow two earlier pre-grant oppositions against patent applications pertaining Combivir and Tenofovir, also filed also by groups of people living with HIV/AIDS.

The movement by AIDS patients to file pre-grant opposition to patent applications is developing at a moment when there is serious public concern whether Indian generic drug companies will be able to continue supplying cheaper generic versions of branded products, both to India and to other developing countries.

Recent studies (reported below) have concluded that a majority of Indian generic firms are facing a situation of reduced incentives to produce generics in future, due to uncertainties following recent amendments to the Indian patent law, and the cumbersome procedures to fulfill requirements of the recent amendments to the TRIPS Agreement of the WTO.

The movement to oppose patent applications is significant in that if patents are not granted on the relevant drugs, then it is far more likely for the Indian companies to produce more affordable generic versions of the drugs.

All the four new pre-grant opposition cases were filed pursuant to Section 25 of the Indian Patents (Amendment) Act, 2005 which allows "any person" to oppose in writing following the publication of a patent application. The opponents are also requesting a hearing with the patent office.

While the details of the oppositions filed differ, the main objective is the same i. e. to promote access to medicines for all in India and abroad. Many developing countries rely on India as their main source of supply of affordable generic medicines.

Thus the Indian situation is being watched closely internationally because of the leading role of Indian companies in the global supply of safe, effective and affordable generic medicines for AIDS and other diseases.

Due to competition by the Indian firms, the cost of HIV/AIDS treatment has dropped from $10,000 to $150 per person per year in recent years. The costs of treating other ailments have similarly been reduced.

When India changed its law in 2005 to allow for product patents for pharmaceutical products, in compliance with its obligations under the TRIPS Agreement of the WTO, there was significant public concern whether Indian-manufactured generic versions of patented medicines would be as readily available as prior to 2005.

One of the new pre-grant cases is against the grant of patent application titled "Pharmaceutical Formulations" (Application no: 727/DEL/1997A) filed on 21 March 1997 by Glaxo Group Limited. The case was submitted by the Indian Network of Positive People (INP+) and the Uttar Pradesh Network for People Living with HIV/AIDS at the Delhi Patent Office.

The groups said that being a signatory of the Doha Declaration on the TRIPS Agreement and Public Health, India must interpret the Patents Act to give effect to the aim outlined in the Declaration i. e. that the TRIPS Agreement should be interpreted and implemented in a manner supportive of the WTO members' right to protect public health and in particular to promote access to medicines for all.

The pre-grant opposition states that the patent application comprises merely of a combination of known substances i. e. a protease inhibitor with tocopherol, or Vitamin E, to achieve a known result. It also states that in a further formulation, known solvents are added to make the combination more flowable and cheaper to manufacture.

The groups thus seek that a patent not be granted on the grounds of lack of novelty and inventive step, both critical criteria in determining patentability. They claim that the alleged inventions are "merely a new use of known substances" that does not result in an enhancement of efficacy as well as a mere admixture, all of which are not patentable under the new amended Indian patent law.

The patent application cites Amprenavir, (a drug that works by inhibiting HIV protease, an enzyme essential for the replication of the virus and used in combination therapies to treat HIV/AIDS) as the preferred protease inhibitor for working the alleged invention.

Another pre-grant opposition case was filed against a patent application titled "2-(2-Amino-1, 6-Dihydro-6-oxo-purin-9-yl)-methoxy-1, 3-propanediol Derivative" by Hoffmann-La Roche (Application No. 959/MAS/95) on 27 July

1995 at the Chennai Patent Office. The case was filed by INP+ and the Tamil Nadu Networking People with HIV/AIDS.

According to the opponents, the patent application relates to valganciclovir which is a pharmaceutical compound that is a pro-drug of another known compound ganciclovir and is a critical treatment for CMV retinitis, a common AIDS-related opportunistic infection that can cause blindness.

The groups say that the application is about an invention that is in the public domain and therefore not new. They add that by the applicant's own admission, an application for patent for the same invention was filed in the US on 28 July 1994. Referring to a press release by the patent applicant itself that states that valganciclovir was discovered in 1994, they said that since the compound was known before 1995 it forms part of the state of the art.

The opponents also affirm that after studying the description of each application, "they are virtually identical".

The groups also claim that the patent application has failed to meet the formal disclosure requirements under Section 8 of the patent law which requires an applicant for patent to furnish the Patent Office with detailed particulars of any patent applications for the same or similar inventions made in any other country and to undertake to update the Patent Officer of detailed particular of every other application made subsequent to filing within the prescribed time.

They further said that the patent applicant failed to reveal an application for a substantially similar invention in the European patent Office as well as subsequent applications, on the same invention re-filed (as the first application filed on 28 July 1994 was abandoned) on 30 May 1995 and again on

4 March 1997 in the US. According to the Patents Act, a failure to comply with Section 8 is a ground for opposition and sufficient ground to reject the patent application in its entirety.

Another of the recent pre-grant opposition cases was filed by INP+ and the Karnataka Network of People Living with HIV/AIDS against a patent application titled "Anti-virally Active Heterocyclic Azahexane Derivatives,"

by Novartis AG (Application No: 805/MAS/1997), filed on 21 April 1997. The application pertains to Atazanavir a vital second-line protease inhibitor.

The opposition to the grant is on the grounds of lack of novelty and inventiveness and the failure to provide the Patent Officer with information as required by Section 8 of the Act.

The opponents said that well before the priority date of the patent application, the HIV protease enzyme had been identified as a key therapeutic target, the three-dimensional structure of the protease enzyme, including a detailed mapping of the active site, had been disclosed, and various assays to determine the inhibitory effect of candidate substances had been developed. Further, there is a wealth of pre-existing technical knowledge in developing effective inhibitors of the HIV protease on which researchers can draw on.

As a result of these and other advancements, several protease-inhibiting compounds had already been patented prior to the priority date of the present application. The opponents said that one of these patents

(WO9419332) discloses compounds that overlap considerably with the compound disclosed in the patent application. At the most, the claimed compound is a new form of a known substance and thus not deserving a patent under the amended patent law.

The opponents also claimed that the applicant failed to disclose two foreign patents i. e. in Europe (EP 0900201, filed 14 April, 1997) and in US (5849911, filed 9 April, 1997) for substantially the same alleged invention, with a title identical as the application filed in India.

They note that in the European patent application, the patent of WO9419332, along with other patents covering similar compounds, was disclosed by the patent applicant, as relevant prior art, although such a discussion is absent from the application filed in India. The opponents submit that this is "inequitable behaviour" on the part of the applicant.

The fourth recent opposition filed by INP+ is against a patent application by the Glaxo Group Limited titled "A Novel Salt"(Application No: 872/CAL/98

A) filed on 14 May 1997. The application relates to the hemisulfate salt of a known compound Abacavir.

The grounds for opposition are that the claimed invention is not new and stand anticipated by prior publication. The group refers to a prior application European Patent 0434450 published on 26 June 1991.

The opponents state that the application fails to meet the test of inventiveness, and presents two prior art publications in support of the contention of obviousness. The opponents also add that the claimed invention is simply a new form of a known substance with no significantly different properties with regard to efficacy and thus not patentable under the India patent law.

If the oppositions are successful, they will clear the way for Indian companies to supply generic versions of these medicines.

The Indian patent law excludes from patentability drugs which have patent priority dates prior to 1995, and thus generics production can continue for these drugs.

For drugs which have patent priority dates between 1995 and 2005, the Act provides that production of generic versions can continue in return for payment of a "reasonable" royalty.

However this provision only applies to "enterprises which have made significant investment and were producing and marketing the concerned product prior to 1st January 2005 and which continue to manufacture the product covered by the patent on the date of grant of the patent" (Section 11A of the Amendment Act). It is not clear which products are and are not covered by the provision.

When patents are granted after the coming into force of the 2005 law, there can be no generic manufacturing unless with the permission of the patent holder, or unless the government issues a compulsory license.

Some studies have given a pessimistic scenario for the Indian generic drug industry and for patients relying on its medicines.

A briefing paper for the UK official aid agency DFID, "Updating on China and India and Access to Medicines" by Cheri Grace (2005), concluded that treatment for cancer and diabetics is most likely to be negatively impacted by the implementation of TRIPS since these are treated with relatively new drug classes which have little therapeutic competition/substitution.

Classes of drugs that experience a high speed of new product development due to emerging resistance such as antibiotics and anti-infectives (e. g. ARVs, TB drugs and anti-malarials) will also be affected, since newer drugs in this group may have little therapeutic competition, while the older drugs are ineffective.

Grace highlights how the lack of access to one drug in a combination therapy (as it is patented) can preclude appropriate treatment, and just a few expensive patented medicines can skew entire health budgets.

Taking into account various estimates, she concludes that 10-15% of the Indian production will initially be affected by product patent protection, and the percentage would increase over time as new, patented medicines become an increasing proportion of the overall market.

A decision was taken by WTO members on 30 August 2003 (which became the basis for an amendment of the TRIPS Agreement on 6 December 2005) to create a mechanism to deal with exporting and importing of drugs to meet the needs of people in countries lacking drug-manufacturing capacity.

The mechanism has been criticized as being too cumbersome as it contains many procedural requirements that the exporting and importing countries have to follow.

A study published by the United Nations University- Institute for New Technologies presented the results of interviews carried out with 103 Indian generic firms, which were asked whether Section 92(a) of the post 2005 Indian Patent Act (that incorporates elements of the 30 August 2003 WTO decision) constituted a favourable economic incentive for exports, especially to least developed countries.

The study was authored by Padmashree Gehl Sampath and is titled "Economic Aspects of Access to Medicines after 2005: Product Patent Protection and Emerging Firm Strategies in the Indian Pharmaceutical Industry".

It found that of the 103 generic firms, only 25 firms thought it was an economically lucrative option, whereas 78 firms did not think so. Of the 25 firms, 15 are small, with little or no experience in exporting pharmaceutical products, and most of them are unable to comply with the WHO's standards for Good Manufacturing Practices and they and have no R & D investments, given their small scale operations.

Only 6 of the large generic companies and 4 of the medium sized generic companies responded positively. Most of the large firms did not think it was a lucrative option due to the increase in procedural hurdles and the low economic returns from using Section 92(A) of the Act. This requires the issuance of a compulsory license in India and the use of several procedural steps by both India and the importing country that would like to make use of the 30 August 2003 Decision.

Some of the medium sized firms also mentioned the constraints posed by the fact that their product range may be very different from the products that the importing countries require.

Moreover they estimated it may not be profitable for them to invest in securing supplies of active pharmaceutical ingredients that are different from those they normally require, or to invest in reverse engineering efforts and technological investments to produce the medicines under a compulsory license.

In another paper, the same author projects that of the 42 Indian firms supplying the African region in 2004-05, only 25 will do so in the future under the requirements of Section 92(A) of the amended Indian patent law.

In the UNU-MERIT working paper, "India's Product Protection Regime: Less or More of Pills for the Poor?", Padmashree Sampath concludes that the Indian generic firms, (especially the large and medium sized firms) no longer view the production of generic versions of pharmaceuticals patented products as a profitable activity in the post-2005 situation.

This is due to the fact that their ability to supply the drugs to different markets and profit from increased sales in now constrained by the introduction of product patent protection in India.

While this may be the case, "regional aggregation of demand by countries which do not have significant manufacturing capabilities" may go a long way to incentivise these manufacturers to produce newly patented drugs under a compulsory license, said the paper.

Even then access to medicines would be hampered by the proviso in the amended Indian patent law that only allows the issuance of a compulsory license after a period of three years from the date of grant of patent.

In this rather bleak scenario, the filing of pre-grant opposition cases against the applications for patents on drugs is a legal option which is being used by groups of people living with HIV/AIDS and which they hope will succeed in preventing the wrongful granting of patents.

If patents are not given to these drugs, then it would be far easier and more profitable for the generic companies to produce their versions, and to supply the markets of India and other developing countries.