D RUG P ATENTING AND ITS E FFECTS ON P HARMACEUTICAL F IRMS With an Emphasis on the Gleevec Patent Case

DRUG PATENTING AND ITS EFFECTS ON

PHARMACEUTICAL FIRMS With an Emphasis on the Gleevec Patent Case

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CONTENTS

Patent Laws in:• India• U.S.A.• China• Russia• Brazil The Gleevec Patent Case Compulsory Licensing

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PATENT LAWS IN INDIA

Patent laws in India are controversial. Ability of pharmaceutical companies to secure

patents affects the drug industry in India. Affects price of drugs in India.

Source: Lee, U. L. (n.d.). TRIALS AND TRIPS-ULATIONS: INDIAN PATENT ACT AND NOVARTIS AG V. UNION OF INDIA. BERKELEY TECHNOLOGY LAW JOURNAL, 23, 281-282.

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2005 AMENDMENT INDIAN PATENT LAW

Due to the 2005 amendment in the Indian Patent Law and intellectual property, multinational pharmaceutical companies benefit more than the domestic drug manufacturers in India.


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SECTION 3(D)

One of the amendments of Patent Law 2005. Protects against unnecessary patenting molecules. Section 3 is the key section on “patent eligibility”

and lists out what are not classified as “inventions” under the Indian Patents Act.


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THE ASSUMPTION BEHIND 3(D)

Derivatives such as salt forms, polymers, isomers that are structurally similar to known pharmaceutical substances are likely to be functionally equivalent as well.

If not and the new form of an existing substance works better than the old form, it is up to the patent application to demonstrate this and justify the claim to a patent.

Source: Reddy, S. B. (2008). 'Ducking' TRIPS in India: A Saga Involving Novartis and the Legality of Section 3(d). National Law School of India Review, 20(2), 131-155.

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SECTION 3(D)NON ELIGIBLE PATENTABLE SUBJECT MATTER

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 process results in a new product or employs at least one new reactant.


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WHY WAS SECTION 3(D) INTRODUCED?

Aims to prevent “ever-greening”.Only those pharmaceutical derivatives that demonstrate significantly enhanced efficacy are patentable.The Indian government introduced Section 3(d) to prevent multinational pharmaceutical companies from extending the life of a patent.


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EVER GREENING

A practice by which pharmaceutical companies attempt to extend patent protection by filing new patents over the process, dosage form, or method of administration, rather than the active ingredient itself Refers to different ways wherein patent owners can

take undue advantage of the law and associated regulatory processes to extend their IP monopoly.

Leads to patent lifecycle enhancement technique largely employed by the pharmaceutical companies to develop bullet proof patents for lucrative drug molecules.


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EVER GREENING

Protection of family of lucrative molecules. Can act as a jackpot to some pharmaceutical

companies, which can retain monopoly. Can lead to a potential loss to competitors. Ever greening strategies include method of

treatment, mechanism of action, dosing regimen, biological targets, isometric forms, screening methods.

Source: Inderjit Singh Bansal, D. S. (2009, July). Evergreening- A Controversial Issue in Pharma Milieu. Journal of Intellectual Property Rights, 14, 299-306.

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EVERGREEN STRATEGIES BY PHARMA COS.

Redundant extensions and creation of next generation drugs which result in superfluous variation to a product and then patenting it as a new application.

Prescription to OTC switch. Exclusive partnerships with cream of generic

players in the market prior to patent expiry.

Source: Inderjit Singh Bansal, D. S. (2009, July). Evergreening- A Controversial Issue in Pharma Milieu. Journal of Intellectual Property Rights, 14, 299-306.

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EVER GREENING BY FIRMS

Losec Omeprazole is sold in Canada by Astra Zeneca Pharma Inc. (“Astra”) under the brand name Losec. , with annual sales in Canada in 2002 of $424 million.

The second highest selling drug product in Canada based on sales dollars.

Sale of generic omeprazole in Canada has been successfully blocked by the ever greening of patents by Astra.

Source: http://www.pharmainfo.net/manandkumar/evergreening-patents-emerging-issue

http://www.pharmainfo.net/manandkumar/evergreening-patents-emerging-issue

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LOSEC OMEPRAZOLE

Losec capsules, Losec MUPS tablets (MUPS = Multiple Unit Pellet System) and Losec injection all contain the active ingredient omeprazole, which is a type of medicine called a proton pump inhibitor.

Omeprazole acts in the stomach to decrease the production of stomach acid.

Proton pumps are found on cells that line the stomach and are used by these cells to produce stomach acid.

Omeprazole works by inhibiting the action of the proton pumps, and this reduces the production of stomach acid.

Omeprazole is also given together with antibiotics to help eradicate bacteria called Helicobacter pylori from the stomach.

Source: http://www.netdoctor.co.uk/digestive-health/medicines/losec.html

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LOSEC OMEPRAZOLE

Omeprazole can also be used to prevent and treat peptic ulcers that can occur as a side effect of non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac. NSAIDs relieve pain and inflammation by reducing the production of substances called prostaglandins.

Source: http://www.netdoctor.co.uk/digestive-health/medicines/losec.html

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EVER GREENING BY FIRMS

After generic companies filed submissions with Health Canada in respect of Omeprazole, Astra switched its omeprazole product from a capsule to a tablet and acquired new 20-year patents on the tablet form.

Several other subsequent patents were listed on the Register in respect of minor modifications to the drug, including patents on a new coating, different dosages and the inactive chemicals used in tablets.

The Patent Register now contains at least 10 additional patents in respect of Losec.



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EVER GREENING BY GSK

Paroxetine is sold in Canada by GlaxoSmithKline (“Glaxo”) (formerly Smith Kline Beecham), under the brand name Paxil.

Paroxetine is an antidepressant with annual Canadian sales in 2002 of $227.5 million.

The listing of patents by Glaxo has resulted in seven-and-a-half years of automatic stays.




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PAROXETINE Generic Paxil is used for treating depression or

obsessive-compulsive disorder (OCD). It may be used to treat panic disorder, posttraumatic

stress disorder (PTSD), generalized anxiety disorder or social anxiety disorder.

The first stay was triggered on December 4, 1996 and expired May 4, 1999.

The ‘base’ patent expired in the late 1990s, but ancillary patents covering new forms, tablets, uses and processes will not expire until between 2006 and 2018.

Source: http://www.reedsportcc.org/store/paroxetine-10-mg-usa.html: CHALMERS, R. (2007, March 5). EVERGREEN OR DECIDUOUS? AUSTRALIAN TRENDS IN RELATION TO THE ‘EVERGREENING’ OF PATENTS. Melbourne University Law Review, 30, pp. 29-33.

http://www.reedsportcc.org/store/paroxetine-10-mg-usa.html

http://www.reedsportcc.org/store/paroxetine-10-mg-usa.html

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EVER GREENING BY GSK

The original inventor of Paroxetine was “Ferrosan”. GSK acquired the rights for the molecule. Thereafter, GSK has acquired several patents for

Paroxetine.

Source: http://www.gnaipr.com/Articles/Evergreening.pdf

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INDIA AND WTO

India joined WTO at the end of the 20th century. Needed to comply with the international standards

for intellectual property. The former policy favoured domestic drug

producers who could produce drugs at cheaper rates than international drug maker

Controversy in India regarding balancing the consumer requirements of low cost drugs versus long term investment in the pharmaceutical industry.


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U.S. PATENT ACT

The general rule is that patents filed today in the United States and most other countries have a term that lasts from issuance until 20 years from the filing date.

The general rule in the United States is that provisional and foreign filings will not count against patent term.

Source: Tamsen V. Valoir, R. L. (2007, April). Calculating Patent Term: A Tricky Business. Intellectual Property & Technology Law Journal, 19(4).

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U.S. PATENT ACT CONTD..

To calculate patent term, begin with the first filed utility or Patent Cooperation Treaty (PCT) application and add 20 years to obtain the patent term.

Next, check for patent term adjustments on the face of the patent or at the Patent Application Information Retrieval system (PAIR) and add the adjustment, if any.

If the patent is for a pharmaceutical product, check the Orange Book, the Federal Register, or the Patent and Trademark Office (PTO) to determine if the patent was awarded any restoration of patent term under 35 U.S.C. § 156.Source: Tamsen V. Valoir, R. L. (2007, April). Calculating Patent

Term: A Tricky Business. Intellectual Property & Technology Law Journal, 19(4).

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THE 17 YEAR METHOD (U.S. PATENT)

The effective date of the change in law to the modern 20-year term was six months after the GATT agreement, or June 8, 1995.

Any patent that had already expired by that date would be governed by the old law and have a 17-year-from-issue term.

Counting backwards from the change in law, the last issue date for patents governed by the old rule is June 5, 1978.

All of the patents that fall under the old rule have already expired.

The patent term for these older patents is calculated using the issue date of the patent and adding 17 years to obtain the patent term. Source: Tamsen V. Valoir, R. L. (2007, April). Calculating Patent Term: A

Tricky Business. Intellectual Property & Technology Law Journal, 19(4).

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PATENT RULES IN CHINA

For applications filed before January 1, 1993, the patent term is 15 years for invention patents and five years for utility model and design patents, each calculated from the Chinese filing date of the application.

The terms for utility model and design patents, but not invention patents, are each extendible for another three years, provided that one files the requisite petition and fees.

For applications filed in China on or after January 1, 1993, the patent term is 20 years for invention patents and 10 years for utility model and design patents, calculated from the Chinese or international filing date, rather

than the priority date.Source: Tamsen V. Valoir, R. L. (2007, April). Calculating Patent Term: A Tricky Business. Intellectual Property & Technology Law Journal, 19(4).

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China does not have patent term restoration for

drug patents. However, China does offer “Monitoring Period

Exclusivity” and “Data Exclusivity,” which are similar

to the non-patent protections offered by the FDA in

the United States for medical products. There is also “Administrative Protection of

Pharmaceuticals,” which is a quasi-patent

protection designed to address the lack of patent

protection in China for pharmaceuticals prior to

1993.Source: Tamsen V. Valoir, R. L. (2007, April). Calculating Patent Term: A Tricky Business. Intellectual Property & Technology Law Journal, 19(4).

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China has overhauled parts of its intellectual property laws to allow its drug makers to make cheap copies of medicines still under patent protection.

Allows Beijing to issue compulsory licenses to eligible companies to produce generic versions of patented drugs during state emergencies, or unusual circumstances, or in the interests of the public.

For "reasons of public health", eligible drug makers can also ask to export these medicines to other countries, including members of the World Trade Organisation.

Source: Reuters

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DRUG PRICING IN RUSSIA

Prior to April 2010, there was a free drug pricing system in Russia, which allowed pharmaceutical companies to choose the price of drugs.

Prices increased dramatically during the 2008-2009 economic crisis, and drug prices in Russia increased by 30% during 2009.

The pricing policy for drugs in Russia was modified after the 2010 implementation of the new law "on the circulation of drugs".

Source: http://www.chemrar.ru/eng/i-news/index.php?ELEMENT_ID=13789

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DRUG PRICING IN RUSSIA

The new law makes it compulsory for drug manufacturers to register the maximum selling prices of drugs on the EDL (Essential Drugs List), which constitutes more than 30% of the Russian pharmaceutical market.

This acts to prohibit drug makers from increasing the cost of listed drugs, helping to prevent inflation of medical treatment costs, and also encourages growth in the Russian pharmaceutical manufacturing market, as foreign drug companies refrain from importing products whose maximum drug prices cannot incorporate import charges.

Source:http://www.chemrar.ru/eng/i-news/index.php?ELEMENT_ID=13789

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BRAZIL PATENT RULES

Brazil passed a TRIPS compliance patent law in 1996. Before this new law, there was an exclusion of

patentability for pharmaceutical products and processes. An important aspect of the 1945 changes in the national

patent laws was the creation of statutory exclusions of patentability for inventions relating to chemical products, food, and pharmaceutical products.

Inventions related to pharmaceutical processes were added to this list in 1969.

Source: Luciano Martins Costa Póvoa, U. o. (n.d.). Innovation in the Brazilian Pharmaceutical Industry post-TRIPS .

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BRAZIL PATENT RULES

The exclusion of patentability for pharmaceutical products proved to be insufficient to promote a robust technological effort by local firms.

It is for this reason that the exclusion of patentability was extended to pharmaceutical processes in 1969.

According to the TRIPS agreement, pharmaceutical inventions could not be excluded from the definition of patentable subject matter.

Source: Luciano Martins Costa Póvoa, U. o. (n.d.). Innovation in the Brazilian Pharmaceutical Industry post-TRIPS .

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PATENT LAWS IN BRAZIL

Brazil signed the TRIPS agreement, with 13 other WTO members. When Brazil signed TRIPS, it automatically had to reorganize its patent regulatory system.

Brazil then approved a patent law in 1996 (Law 9279) and the next year approved a plant variety protection law (Law 9456).

These adjustments came a few years after TRIPS, and the Brazilian patent law incorporated what was minimally required in the TRIPS Agreement.

Source: http://blogs.nature.com/tradesecrets/2011/08/17/the-patent-system-in-brazil

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The Brazilian law incorporated TRIPS-endorsed principles that were never accepted by the international pharmaceutical sector, particularly compulsory license.

The Brazilian law allows for patented products to be manufactured in Brazil if it’s deemed that prices established by pharmaceutical companies (mostly multinationals) are abusive.


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Next the Brazilian government, under the stimulus of the health public sector, modified the Patent Law and established with ANVISA (equivalent to FDA in the USA and to EMEA in Europe) that those willing to patent in pharmaceuticals, and having applied for this purpose at the National Institute of Intellectual Property, needed an agreement from ANVISA.

This rule makes the Brazilian process longer than any other in the world, and it is under judicial dispute.


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The Brazilian Patent Law is very restrictive, as we can see in the Article 18 of the Law, which deals with biology matters.

The Law 9279 prevents patenting parts of organisms, be it microorganism, plant or animal. Cells are not patentable .

Genes are not patentable, unless essential for a patented process.


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Biopharmaceuticals are not patentable. Molecules derived from the huge Brazilian biodiversity are not considered inventions even if these molecules are isolated and their function demonstrated.

As a result Brazil has not one molecule patented from our biodiversity.


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FOREIGN FIRMS CONCERN ABOUT 3(D) IN INDIA

Pharmaceutical companies spend billions of dollars on research for developing a single product.

A company has to spend approximately $800 million and 15 years to bring a drug into the market.

It is estimated that, of every thousand potential drugs screened, only four to five reach the clinical trial stage and only one actually gets approved for marketing.

The exclusive rights given to pharmaceutical companies as patentee for 20 years, facilitates them to recover their investments.

Source: INTERPRETATION OF SECTION 3(D) IN THE INDIAN PATENTS ACT 2005: A case Study of Novartis.

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FOREIGN FIRMS CONCERN ABOUT 3(D) IN INDIA

The prices of such medicines depend upon the pricing strategies and profit margins of each company.

They sell drugs at a high price to replenish the research and development costs.

This may lead to unaffordable prices of patented medicines in developing countries.

Under Section 3(D), they can not file for a patent for all drugs.

The terms and conditions under Section 3(D) are unclear.

Foreign firms are concerned that the local firms will copy their substances and sell at a cheaper price, ruining the foreign firms’ business.


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SUMMARY OF PATENT RULES

Section 3DWTO member TRIPS Patent Term

Compulsory Licensing

COUNTRY

INDIA YES YES YES 20 years YES

RUSSIA NO NO NO 20 years YES

CHINA NO YES YES 20 years YES

BRAZIL NO YES YES 20 years YES

USA NO YES YES 20 years YES

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LABCORP CASE

Laboratory Corp. of America v. Metabolite Labs, Inc. (LabCorp) case.

The first case in which the Supreme Court would address the question of what constitutes patentable subject matter under 35 U.S.C. § 101 2 since its landmark decision in Diamond v. Diehr.

Source: Tyler, Lynn C (2007), “Genes and 35 U.S.C. § 101: Are DNA Sequences Corresponding to Gene Patentable Subject Matter,”?Intellectual Property & Technology Law Journal . 19( 6)

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LABCORP CASE PROBLEM

Whether a method patent setting forth an indefinite, undescribed and non-enabling step directing a party simply to “correlat[e]” test results can validly claim a monopoly over a basic scientific relationship used in medical treatment such that any doctor necessarily infringes the patent merely by thinking about the relationship after looking at a test result.


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WHY DEBATE OVER PATENTS?

More than 2000 patents have been issued to different pharmaceutical companies.

The magnitude of these patents have generated debate within the scientific, legal, and other communities over whether private parties should even be allowed to patent genes or other DNA sequences.


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WHAT IS PATENTABLE?

35 U.S.C. § 101 defines patentable subject matter as “any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof . . . .”

Congress adopted § 101 in 1952, the Supreme Court has held that “Congress intended statutory subject matter to ‘include anything under the

sun that is made by man.’


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WHAT IS NOT PATENTABLE?

In 1853, the Supreme court wrote that “the discovery of a principle in natural philosophy or a physical science is not patentable.”

Laws of nature, natural phenomena, and abstract ideas. New mineral discovered in the earth or a new plant found

in the wild is not patentable subject matter.


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WHAT IS NOT PATENTABLE?

Patents cannot be issued for the discovery of the phenomena of nature.

Manifestations of laws of nature, free to all men are reserved exclusively to none.

He who discovers a hitherto unknown phenomenon of nature has no claim to a monopoly of it which the law recognizes.


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HOW WAS GLEEVEC DISCOVERED?

In 1960, Peter Nowell, a faculty member at the University of Pennsylvania School of Medicine, alongwith a grauduate student discovered a genetic mutation in patients with Chronic Myelogenous Leukemia (CML).

This discovery was named “Philadelphia chromosome”- a potential cure for CML.

In the 1990s, researchers modified this chromosome into a free base called “Imatinib”.


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MECHANISM OF ACTION OF IMANITIB

Source: Wikipedia

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HOW DOES THE DRUG WORK?

Gleevec (imatinib mesylate) film-coated tablets contain imatinib mesylate equivalent to 100 mg or 400 mg of imatinib free base.

Imatinib mesylate is designated chemically as 4-[(4Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]benzamide methanesulfonate and its structural formula.

Imatinib mesylate is a white to off-white to brownish or yellowish tinged crystalline powder.

Source: K.D. Raju. INTERPRETATION OF SECTION 3(D) IN THE INDIAN PATENTS ACT 2005: A case Study of Novartis.

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Its molecular formula is C29H31N7O • CH4SO3 and its molecular weight is 589.7.

Imatinib mesylate is soluble in aqueous buffers = pH 5.5 but is very slightly soluble to insoluble in neutral/alkaline aqueous buffers.

In non-aqueous solvents, the drug substance is freely soluble to very slightly soluble in dimethyl sulfoxide, methanol and ethanol, but is insoluble in n-octanol, acetone and acetonitrile.


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Imatinib is a type of targeted therapy known as a tyrosine kinase inhibitor.

Its targets include tyrosine kinase proteins. These abnormal proteins are found at the surface of certain cancer cells.

They send constant signals telling the cells to divide and stay alive.

By blocking these signals, imatinib can stop the cells from growing and cause them to die.

Source: http://www.cancer.org

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NOVARTIS AND GLEEVEC

Novartis filed a patent for “Imatinib”. Imatinib was further researched and converted to

“imatinib mesylate”. Novartis later formulated the beta crystalline form of

Imatinib into a pharmaceutically useful drug, “Glivec”.


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GLEEVEC

Source: missionpossible-svmb.com

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IMPORTANCE OF GLEEVEC

Gleevec represents a new class of cancer drugs and a new way of thinking about cancer. These molecularly targeted drugs are different because they target abnormal proteins that are fundamental to the cancer itself.

Large number of population in India is poor. Indian patients can not afford Gleevec. If patented, Gleevec will become very expensive.


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ABOUT GLEEVEC

Gleevec (imatinib) interferes with the growth of some cancer cells.

Gleevec is used to treat a certain types of leukemia (blood cancer) such as Philadelphia chromosome positive chronic myeloid leukemia (CML).

It is also used to treat certain tumors of the stomach and digestive system.

Source: http://www.drugs.com/gleevec.html

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ABOUT GLEEVEC

It turns off the signal of a protein known to directly cause the cancer and has been shown to be considerably more effective than conventional therapy for CML.

Gleevec is a new type of cancer drug – the first of its kind developed to fight cancer by turning off an enzyme that causes cells to become cancerous and multiply.

Source:http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110505.htm

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HOW GLEEVEC WORKS

Source: www.cancer.gov

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ADVANTAGES OVER OTHER CANCER DRUGS

Its action is different than other cancer drugs in that it specifically targets an enzyme that allows CML cells to grow.

It can be given by mouth instead of by injection. CML seems to respond relatively quickly (within one

to three months) to the drug. This response can be measured by tests that show that the blood count returns to a normal range or tests that measure cancer cells in the bone marrow.

Source:http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110505.htm

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IMPACT OF GLIVEC ON INDIA

In 2004, Novartis approached the court for restraining generic manufacturers from producing the generic version of the drug. Once the generic manufacturers stopped producing Glivec, the price of the drug rose from approximately Rs.10,000 for a month’s requirement to a whopping Rs.1,20,000/-.Question of the social cost of protection of higher intellectual property and the ability of the government of a developing country to maintain public health.


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PRICE OF GLIVEC PRE AND POST EMR

Novartis sold Gleevec at USD 2666 per patient per year.

Generic companies had been selling their generic versions at USD 177 to USD 266 per patient per month.


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PATENT APPLICATION FOR GLEEVEC

Until January 2005, drug patents were unavailable in India.

Due to this, Novartis claimed Gleevec in a mailbox application.

This application was examined. The grant of patent was opposed by drug

companies and NGOs. The patent application was rejected.


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NOVARTIS AND GLEEVEC IN INDIA

Novartis AG and Novartis India filed two writ petitions in the Madras High Court.

The petition sought a reversal of the Assistant Controller’s order and declared that Section 3(d) was unconstitutional and was violating India’s obligations under TRIPS.

The High Court transferred the first petition to the Intellectual Property Appellate Board (IPAB).


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IPAB

The Indian judicial system comprises specialized tribunals, including the Intellectual Property Appellate Board (IPAB).

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GLEEVEC

When Novartis challenged the rejection of patent for Gleevec, it was the first major legal challenge to India's newly amended patent law.

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YEAR EVENT SOURCE

1993 The invention of Glivec's base compound, Imatinib mesylate, was patented.

Economic Times

2001 Gleevec launched worldwide. Hindubusinessline.com

2004 Novartis approached the court for restraining generic manufacturers from producing the generic version of the drug.

INTERPRETATION OF SECTION 3(D) IN THE INDIAN PATENTS ACT 2005: A case Study of Novartis

2005 India resumed granting drug patents as part of a World Trade Organization agreement on patents.

NYTimes

2006 The Madras Patent Office rejected Novartis' patent application for Glivec.

Economic Times

2007 Novartis lost its challenge to strike out Section 3(d) provision of the Indian Patent Law.

Economic Times

2012 The final arguments in the Indian Supreme Court case of Novartis vs. Government of India Section 3(d) patent case.

www.expresspharmaonline.com

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CHRONOLOGY OF GLEEVEC CASE

1993- the invention of Glivec's base compound, Imatinib mesylate, was patented. (Source- economic times)

2001- Gleevec launched worldwide.(Source- hindubusinessline.com)

2004- Novartis approached the court for restraining generic manufacturers from producing the generic version of the drug.( Source: INTERPRETATION OF SECTION 3(D) IN THE INDIAN PATENTS ACT 2005: A case Study of Novartis.)

2005- India resumed granting drug patents as part of a World Trade Organization agreement on patents. (Source- NYTimes)

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2006- The Madras Patent Office rejected Novartis' patent application for Glivec. (Source- economic times)

2007- Novartis lost its challenge to strike out Section 3(d) provision of the Indian Patent Law. (Source- economic times)

August 2012-The final arguments in the Indian Supreme Court case of Novartis vs. Government of India Section 3(d) patent case. (Source: www.expresspharmaonline.com)

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India stopped granting drug patents in 1970. Imatinib is a molecular compound developed by

Novartis in 1993. The invention of Glivec's base compound, Imatinib

mesylate, was patented in 1993, and is therefore not eligible for a patent in India.

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Gleevec was approved by the United States Food and Drug Administration in 2001

Gleevec was launched worldwide in 2001. Gleevec was granted EMR in the Indian market in

2003. India resumed granting drug patents in 2005 as part

of a World Trade Organization agreement on patents, but medicines created before 1995 did not qualify.

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Novartis legal action started when it attempted to obtain an Indian patent on Gleevec/Glivec (imatinib mesylate), its drug for chronic myeloid leukaemia and other cancers, which was denied by India's Patent Office in 2006.

In an order dated January 25, 2006, the Assistant Controller of Patents and Designs, Chennai Patent Office rejected the Novartis application.

Source: www.pharmatimes.com

http://www.pharmatimes.com/

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JANUARY 2006 ORDER Novartis AG and its Indian subsidiary, Novartis India Ltd.,

filed writ petitions, in the Madras High Court challenging the decision of the Controller.

The petitioner alleged that Section 3(d) of the Patents Act, 1970, as amended by the Patents (Amendment) Act, 2005, is invalid, illegal and unconstitutional on the ground that there is arbitrary power vested in the executive according to Article 253 read with Article 73 of the Constitution of India.

The petitioner, further, submitted that when enacting Section 3(d) of the Patents Act, the legislature had completely ignored the rationale underlying Articles 253 and 51(c) of the Indian Constitution, which allows the Parliament to mould municipal law in harmony with international treaties like the TRIPs Agreement of which India is a party.


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JANUARY 2006 ORDERARGUMENTS OF THE ASSISTANT CONTROLLER

Section 3(d) holding that the subject compound did not differ significantly in properties with regard to efficacy as compared to the known compound despite recording that there was a 30 per cent increase in bio-availability of the subject compound over the known substance.

Anticipation by prior publication, i.e., the subject compound is already discussed in public documents and, thereby, destroying the novelty of the invention.

On the question of obviousness, the Assistant Controller has held that the subject compound is in the obviously naturally occurring form and there was no inventive step involved.


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The Assistant Controller concluded that imatinib mesylate was already known from prior publications because Claims 6 to 23 of the U.S. Patent application, a pharmaceutically acceptable salt of the base compound and the patent term extension certificate, specifically mentions imatinib mesylate as the product in the earlier patent application.

Furthermore, the U.S. Patent discloses methanesulphonic acid as one of the salt forming groups and the patent specification clearly states that the required acid addition salts are obtained in a customary manner.


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Also that imatinib mesylate normally exist in the beta crystals form, which is thermodynamically a very stable product and, thus, the invention is obvious and anticipated by prior publication.

For these reasons, it is not an invention under the Indian Patents Act, 2005.


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THE PETITIONER’S CLAIMS

The petitioner alleged that the decision of the Assistant Controller violated the principles of administrative law crystallised and reiterated by the decisions of the Supreme Court of India, in particular the Wednesbury principle.

In the Novartis case, the petitioners claimed that they had invented a particular form of methanesulfonic acid addition salt of a particular Pyrimidineamine Derivative (Imatinib Mesylate) in the crystal form.


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THE PETITIONER’S CLAIMS Additionally, it was claimed that the petitioners had

invented the substance in two forms – Alpha and Beta- of which the Beta form can be stored easier, is less hygroscopic, easier to process and guarantees a constant quality of the final drug product.

The Beta crystalline form of imatinib mesylate also results in higher bio- availability over the 1993 compound and, hence, differs significantly in properties with respect to efficacy.

The Beta crystalline form of imatinib mesylate was being produced and sold on a commercial scale in India from 2003 after getting EMR.


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OPINIONS OF GENERIC MANUFACTURERS

The generic manufacturers and civil society organisations alleged that Novartis’ invention lacked novelty, and was obvious to a person skilled in the art, and that it was merely a new form of a known substance that did not enhance the efficacy of the substance, and therefore, it was not patentable under Section 3(d) of the Patents Act.

Different crystalline forms of imatinib mesylate did not differ in properties with respect to efficacy, and thus, the various forms of imatinib mesylate must be considered the same substance under Section 3(d).


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OPINIONS OF GENERIC MANUFACTURERS

These arguments were based on the fact that Novartis had already been granted a patent in 1993 for the active molecule, imatinib, and that the present application only concerned a specific crystalline form of the salt form of that compound.

It should be observed that Novartis’ 1993 patent disclosed both the free base, imatinib, and the acid-addition salt, imatinib mesylate and the crystalline forms of imatinib mesylate claimed in the application in question do not significantly differ in properties with respect to efficacy.


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NOVARTIS’ CLAIMS

The 1993 patent was for synthesizing the molecule of imatinib.

This molecule, could not be administered to patients and represented only the first step in the process to develop Glivec.

Novartis developed the mesylate salt of imatinib and then the beta crystal form of imatinib mesylate to make it suitable for patients to take in pill form.

Glivec was launched globally in 2001, and this is the only form of Glivec Novartis has marketed.


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NOVARTIS’ CLAIMSThe subject compound is two step removed from the prior art as it is a two-fold improvement over the prior art- first, the imatinib free base had been chemically changed into a salt form (the methanesulfonic acid addition salt) and second, a particular crystal form of this salt, i.e., the beta crystal form which had been made through ingenuity and human intervention.Interestingly, the petitioners claimed that even if it were a discovery of a new form of a known substance, they could claim the patent because, it had resulted in the enhancement of the known efficacy of the known substance, i.e., imatinib free base, thereby making the subject compound more efficacious. Since the expression discovery has not been defined in any section of the amended Patents Act, it could be construed in the ordinary meaning.


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THE MADRAS HIGH COURT JUDGEMENT

The complainant prayed to the Court to declare Section 3(d) of the Patents (Amendment) Act, 2005, as inconsistent with the TRIPs Agreement and violative of Article 14 of the Indian Constitution.

The second prayer was to allow petitioner’s patent application bearing No.1602/NAS/98 filed before the Madras Patent Office seeking patent.

The whole argument with regard to the violation of Article 14 of the Constitution of India was based on arbitrary discretionary power vested in the Patent Controller in the determination of enhanced efficacy.


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The respondents argued that Section 3(d) has complied with the TRIPs Agreement and that the High Court was not the right forum to determine the issue rather the WTO Dispute Settlement Body (DSB) would be the appropriate forum.

It was argued that the Members are free to adopt laws within the framework of the TRIPs Agreement, and to adopt and implement national policies, like, the right to health for its citizens.


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The Court mainly considered the jurisdictional issue. The petitioner cited the Privy Council decision in Equal Opportunities Commission & Another v. Secretary of State for Employment (referred to Equal Opportunities Commission case”).

In this case, the question under consideration was whether judicial review is available for the purpose of securing a declaration that certain United Kingdom primary legislation is incompatible with European Community Law.


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The House of Lords held that this is a private law claim and dismissed the appeal, but declared the Employment Protection (Consolidation) Act, 1978, was incompatible with Article 119 of the EEC Treaty and Council Directive (EEC) 75/117 and Council Directive (EEC) 76/207.

The petitioner argued for a similar declaration in this case, emphasizing that Section 3(d) was not in consonance with the TRIPs Agreement.

But the High Court agreed with the respondents’ argument that the Equal Opportunities Commission case can be distinguished on facts and cannot be said to be applicable in the present case.


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The High Court on that jurisdiction point held that: “… any International Agreement possesses the basic nature of an ordinary contract and when courts respect the choice of jurisdiction fixed under such ordinary contract, we see no compelling reasons to deviate from such judicial approach when we consider the choice of forum arrived at in International Treaties. Since we have held that this court has no jurisdiction to decide the validity of the amended section, being in violation of Article 27 of TRIPS…”


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The High Court refused to look into the question of whether a private party has a right to enforce an international agreement or whether the Patents (Amendment) Act, 2005, is compatible with the TRIPs Agreement.

Before dismissing the petitions, the Court observed that the “…object which the Amending Act wanted to achieve was namely, to prevent ever-greening; to provide easy access to the citizens of this country to life saving drugs and to discharge their Constitutional obligation of providing good health care to it's citizens.”


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THE PRESENT STATUS

The long-running legal actions continue their course in India's Supreme Court today, following defeat in the initial case in 2007 and a subsequent appeal in 2009.

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ARGUMENTS OF THE OPPONENTS

The rules applied in the wealthy countries can not be applied in India.

Gleevec is a modification to an existing drug (Imantib) and therefore can not be patented according to the Patent Law in 2005.

Gleevec does not represent true innovation.

Source:http://www.swissinfo.ch/eng/business/Novartis_awaits_cancer_drug_ruling_in_India.html?cid=32197530

http://www.swissinfo.ch/eng/business/Novartis_awaits_cancer_drug_ruling_in_India.html?cid=32197530




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ARGUMENTS OF NOVARTIS

We do not want people to copy our substance without having done any research and then distribute the product cheaply and ruin our business.

Novartis argues that Gleevec does not fall into the category of a modified drug (which can not be patented in India).

Source:http://www.swissinfo.ch/eng/business/Novartis_awaits_cancer_drug_ruling_in_India.html?cid=32197530





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ARGUMENTS OF NOVARTIS

Novartis claims that the active ingredient in Gleevec (Beta crystalline form of imatinib mesylate) is more effective than the imatinib free base , as it displays better bio diversity properties.

This claim was rejected by the Assistant Controller.


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ARGUMENTS OF NOVARTIS The petitioner alleged that Section 3(d) of the Patents

Act, 1970, as amended by the Patents (Amendment) Act, 2005, is invalid, illegal and unconstitutional on the ground that there is arbitrary power vested in the executive according to Article 253 read with Article 73 of the Constitution of India.

The petitioner, further, submitted that when enacting Section 3(d) of the Patents Act, the legislature had completely ignored the rationale underlying Articles 253 and 51(c) of the Indian Constitution, which allows the Parliament to mould municipal law in harmony with international treaties like the TRIPs Agreement of which India is a party.


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THE LATEST UPDATE

The final arguments in the Indian Supreme Court case of Novartis vs. Government of India Section 3(d) patent case, will be held on August 22, 2012.

Source: www.expresspharmaonline.com

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COMPULSORY LICENSING

Compulsory licensing is when a government allows someone else to produce the patented product or process without the consent of the patent owner.

It is one of the flexibilities on patent protection included in the WTO’s agreement on intellectual property — the TRIPS (Trade-Related Aspects of Intellectual Property Rights) Agreement.

Source: WTO

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COMPULSORY LICENSE

India's granting of its first-ever compulsory license to a generic firm - for Bayer's cancer drug Nexavar.

India's Controller of Patents - the highest authority of the Indian Patent Office ,has granted Indian generics company Natco Pharma Ltd the compulsory license for Nexavar, which is used in the treatment of liver and kidney cancers.

Source: http://www.pharmatimes.com/article/12-03-12/India_s_first-ever_compulsory_license_-_a_game-changing_move.aspx

http://www.pharmatimes.com/article/12-03-12/India_s_first-ever_compulsory_license_-_a_game-changing_move.aspx



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NEXAVAR

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COMPULSORY LICENSE

The Ecuadorian government has issued its first compulsory license for lopinavir/ritonavir, a key medication in the treatment of HIV/AIDS.

The compulsory license for ritonavir was granted by the Ecuadorian government to Eskegroup SA on 14 April, a Latin American distributor headquartered in Guayaquil for CIPLA, a leading Indian generic drug producer.

Source: http://www.twnside.org.sg/title2/wto.info/2010/twninfo100502.htm

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COMPULSORY LICENSE

The patent for ritonavir, sold under the brand-name Kaletra, is held by the US-based pharmaceutical company Abbott Laboratories.

The compulsory license was issued by the national Ecuadorian Institute of Intellectual Property (IEPI), and the term of application of the license is until 14 November 2014.


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COMPULSORY LICENSE

According to the IEPI document, on 5 January 2010, Eskegroup SA submitted to IEPI an application for a compulsory license to be granted for ritonavir, following which on 15 January, IEPI issued instructions for the granting of compulsory licenses for patented drugs.

On 19 February, Eskegroup SA submitted the required documents concerning its application, and Abbott Laboratories was duly notified of the application by IEPI.


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COMPULSORY LICENSE

In issuing the compulsory license, the IEPI cited amongst others the Constitution of the Republic of Ecuador, the Universal Declaration of Human Rights, Article 31 of the WTO TRIPS Agreement and the Doha Declaration on the TRIPS Agreement and Public Health.


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RITONAVIR COMPULSORY LICENSE

The compulsory licence has been granted for the time that was left on the patent, until 30 November 2014.

Ecuador is setting an example for countries that seek to expand access to life-saving medicines, but struggle to pay for ever-more expensive drugs.

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RITONAVIR (NORVIR)

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ABOUT RITONAVIR

Ritonavir is an antiviral medication in a group of HIV medicines called protease (PRO-tee-ayz) inhibitors.

Ritonavir prevents human immunodeficiency virus (HIV) cells from multiplying in your body.

Ritonavir is used to treat HIV, which causes acquired immunodeficiency syndrome (AIDS). Ritonavir is not a cure for HIV or AIDS.

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ABBOTT’S OPINIONAbbott developed the first test for HIV more than 25 years ago and has continued to invest in the development of new treatments, tests and clinical protocols for HIV since then.Abbott’s lopinavir/ritonavir is the most broadly available antiretroviral treatment in the world and forms the cornerstone of second-line treatment in developing countries – where the majority of people with HIV live. Abbott has invested in sufficient manufacturing capacity and has consistently made the medicine available at prices that are competitive with those of generic manufacturers.Abbott’s HIV medicines are affordable and sold at prices that are competitive with those of generic producers.

Source: http://www.ip-watch.org/2010/04/22/ecuador-grants-first-compulsory-licence-for-hivaids-drug

Documents

D RUG P ATENTING AND ITS E FFECTS ON P HARMACEUTICAL F IRMS With an Emphasis on the Gleevec Patent Case