July 18, 2018:
Patentability of Medicines and Drugs By Varun Gupta (Download PDF)
The Author, Varun Gupta, is a 3rd year student of Chanderprabhu Jain College of Higher Studies and School of Law, New Delhi. He is currently interning with LatestLaws.com.
Introduction
Patent is one of the major forms of Intellectual Property Rights (IPRs) used in the pharmaceutical industry. Trade mark, industrial design, geographical indication and copyright are other forms of IPRs available in India. Grant of patent in India is governed under the Patents Act, 1970.Significant changes like provision of product patents and increase in the term of patent to 20 years were introduced in the Indian patent law, after India signed TRIPS (Trade Related Aspects of Intellectual Property Rights) agreement in 1995. This review provides a brief overview of development of patent law in India as a consequence of TRIPS agreement.
Criteria of patentability and different types of pharmaceutical patents currently being granted in India are described with the aim to provide the fundamental knowledge of pharmaceutical patenting to the researchers.
Other relevant provisions related with patenting of pharmaceuticals like section 3(d), transfer of the patent rights, compulsory licensing etc. are explained with suitable example.
What is a Generic Drug?
A generic drug is a drug that is not branded but is similar to a branded or reference listed drug in terms of dosage, administration and performance.
According to guidelines from the United States Food and Drug Administration (FDA), the generic drug must have the same active ingredient as the brand name drug as well as the same dosage, strength, safety, conditions of use and route of administration.
The generic drug is bioequivalent to the branded product, meaning there is either no significant difference between the two drugs in terms of the rate and extent of absorption or if there is a difference, it is either intended or not medically significant.
So long as the FDA criteria are met, a generic drug may be marketed when the patent protections ends or the patent owner waives its rights. The competitive nature of the drug market means that once the generic drug is available, the cost of the drug is substantially lowered for both the original brand name product and the generic drug.
Every drug that has been developed by the original company has patent protection, which lasts for a variable amount of time, depending on the molecule. In the United States, for example, drug patents only last for about twenty years. Furthermore, these patents apply from well before clinical trials have begun testing the safety and efficacy of the medication. This means that the effective patented life of the drug, which begins after the drug has been approved, may only be seven to twelve years, for example. The majority of drugs, particularly the life saving ones, are then manufactured and sold as generic drugs.
One example of a well known generic drug is metformin, which is used to lower blood sugar levels in diabetes. Metformin is the generic form of a drug which is also available under the brand name Glucophage.
PROCEDURE
When a pharmaceutical company first develops a new drug to be used for a disease condition, it is initially sold under a brand name by which the clinicians can prescribe the drug for use by patients. The drug is covered under patent protection, which means that only the pharmaceutical company that holds the patent is allowed to manufacture, market the drug and eventually make profit from it.
In most cases, the drug patent is awarded for around twenty years in the United States. The lifetime of the patent varies between countries and also between drugs. Since the company applies for a patent long before the clinical trial to assess a drug’s safety and efficacy has commenced, the effective patent period after the drug has finally received approval is often around seven to twelve years.
Once the patent has expired, the drug can be manufactured and sold by other companies. At this point, the drug is referred to as a generic drug. According to guidelines in most countries, including those from the US FDA, generic drugs have to be identical to the branded drug in terms of efficacy, safety, usage, route of drug administration, pharmacokinetics and pharmacodynamics.
Therefore, a drug can be manufactured as a generic drug when the following apply:
- Its patent has expired
- The company that would manufacture the generic drug certifies that the patents held on the drug are either unenforceable, are invalid or would not be infringed upon
- There has never been any patents on the drug before
- In countries where the drug has no patent protection
Once the generic drug is on the market, the monopoly of the patent holder is removed. This encourages competition and results in a significant drop in drug costs, which ensures that life-saving and important drugs reach the general population at comparative prices.
The company holding the initial patent may, however, renew the patent by forming a new version of the drug that is significantly changed compared to the original compound. However, this may require new clinical trials and re-application of the patent. Furthermore, the new compound may have to compete with the original generic molecule on the market, unless the drug regulators find faults and remove the original from the market altogether.
Types of Drugs
One of the key classifications is between traditional small molecule drugs; usually derived from chemical synthesis, and biologic medical products; which include recombinant proteins, vaccines, blood products used therapeutically (such as IVIG), gene therapy, and cell therapy (for instance, stem cell therapies).
Pharmaceutical or drug or medicines are classified in various other groups besides their origin on the basis of pharmacological properties like mode of action and their pharmacological action or activity,[7] such as by chemical properties, mode or route of administration, biological system affected, or therapeutic effects. An elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System (ATC system). The World Health Organization keeps a list of essential medicines.
A sampling of classes of medicine includes:
- Antipyretics: reducing fever(pyrexia/pyresis)
- Analgesics: reducing pain(painkillers)
- Antimalarial drugs: treating malaria
- Antibiotics: inhibiting germgrowth
- Antiseptics: prevention of germ growth near burns, cutsand wounds
- Mood stabilizers: lithiumand valpromide
- Hormone replacements: Premarin
- Oral contraceptives: Enovid, "biphasic" pill, and "triphasic" pill
- Stimulants: methylphenidate, amphetamine
- Tranquilizers: meprobamate, chlorpromazine, reserpine, chlordiazepoxide, diazepam, and alprazolam
- Statins: lovastatin, pravastatin, and simvastatin
Pharmaceuticals may also be described as "specialty", independent of other classifications, which is an ill-defined class of drugs that might be difficult to administer, require special handling during administration, require patient monitoring during and immediately after administration, have particular regulatory requirements restricting their use, and are generally expensive relative to other drugs.
Licences for Manufacturers of Pharmaceutical Products Notes for the guidance of applicant
Under the Pharmacy and Poisons Ordinance, “manufacture” means (a) the preparation of pharmaceutical products, from purchase or acquisition of materials, through processing and packaging, to their completion as finished products for sale or distribution; or (b) the repackaging of pharmaceutical products as finished products for sale or distribution. “Manufacturer” has a corresponding meaning. It shall not include the individual dispensing on a prescription or otherwise of any pharmaceutical products. 2. Part 7 of the Pharmacy and Poisons Regulations relates to the licensing of pharmaceutical manufacturers. A person must not manufacture any pharmaceutical product on any premises unless he is the holder of a licence to manufacture pharmaceutical products on those premises.
The licensing authority is the Pharmacy & Poisons (Manufacturers Licensing) Committee (“the Committee”), an Executive Committee established under the Pharmacy and Poisons Board (“the Board”). The criteria which the Committee must consider in granting a manufacturer’s licence include but are not limited to the following: (a) pharmaceutical products are manufactured by or under the supervision of a registered pharmacist or a person approved by the Board; (b) at least one authorized person is employed to be responsible for ensuring and certifying that each batch of the pharmaceutical products has been manufactured and checked in accordance with the GMP Guide; and the registrable particulars of each batch of the pharmaceutical products correspond exactly with the registered particulars of the products; (c) proper labelling of pharmaceutical products manufactured; (d) premises used in the manufacturing, testing and dispatch of pharmaceutical products being suitable for the purpose; (e) adequate hygiene control of personnel and premises to avoid contamination of pharmaceutical products; (f) retention of a control sample and all related records; (g) compliance with the GMP Guide issued by the Board; (h) results of pre-licensing inspection, which is conducted for all new applications to evaluate whether the premises under application are fit for the licence purposes; (i) previous drug-related conviction(s), in particular those have significant impact to the public interest, of the applicant or his key personnel, if applicable; and (j) previous disciplinary action(s) against the applicant or his key personnel, if applicable. 5. The Committee may revoke a licence to manufacture pharmaceutical products or suspend it for a period it thinks fit, issue a warning letter, or vary a condition of the licence, if, in the Committee’s opinion, the licensed manufacturer has contravened a condition of the licence or any of the regulations provided by the Pharmacy and Poisons Regulations, a code of practice applicable to the licensed manufacturer or the GMP Guide, or has been convicted of a drug-related offence.
(Natco Pharma Ltd., India vs Bayer Corporation, USA)[18]:
In a landmark decision on 9th March 2012, Mr. P. H. Kurian, the then Controller of Patents issued the order of grant of first compulsory license for patents in India. The compulsory license was issued to Natco Pharma Ltd. in patent number 215758 granted to M/S Bayer Corporation. This patent relates to drug Sorafenib tosylate sold under the brand name Nexavar by Bayer. Nexavar is indicated in Renal Cell Carcinoma - RCC (kidney cancer) and Hepatocellular Carcinoma – HCC (liver cancer).
After getting this compulsory license Natco is now free to manufacture and sell a generic version of Nexavar in RCC and HCC. Natco will have to pay a 6% royalty on the net sales to Bayer at the end of each quarter. Further, it can not charge more than Rs 8800 for a monthly dose of 120 tablets of the drug. Natco has also committed to donate free supplies of the medicines to 600 needy patients each year as a condition of the compulsory license agreement.
Above decision was based on the grounds for the grant of compulsory license mentioned under section 84 of the Patents Act, 1970. Controller found that the reasonable requirements of the public with respect to the patented invention had not been satisfied since only 2% of the total kidney and liver cancer patients were able to access the Bayer’s drug. The Controller determined that the patented invention was not available to the public at a reasonably affordable price because Bayer was charging about Rs 2.8 lakhs for a therapy of one month of the drug. The Controller also found that the patented invention was not worked in the territory of India since Bayer was not manufacturing the product in India rather it was importing it from out side India.
How long does an exclusivity period last?
It depends on what type of exclusivity is at issue.
- Orphan Drug Exclusivity (ODE) – 7 years
- New Chemical Entity Exclusivity (NCE) – 5 years
- Generating Antibiotic Incentives Now (GAIN) Exclusivity– 5 years added to certain exclusivities
- New Clinical Investigation Exclusivity – 3 years
- Pediatric Exclusivity (PED) – 6 months added to existing Patents/Exclusivity
- Patent Challenge (PC) – 180 days (this exclusivity is for ANDAs only)
- Competitive Generic Therapy (CGT) - 180 days (this exclusivity is for ANDAs only)
See 21 C.F.R. 314.108, 316.31, 316.34 and sections 505A, 505E, 505(j)(5)(B)(iv), and Section 505(j)(5)(B)(v) of the FD&C Act.
When should an NDA holder submit patent information?
Patent information is required to be submitted with all new drug applications (NDAs) and certain supplemental applications (sNDAs) on Form FDA 3542a at the time of submission of the NDA or sNDA. Patent information for listing in the Orange Book must be submitted on Form FDA 3542 within 30 days following approval of an NDA or supplemental application. For patents issued after approval of the NDA or supplement, the NDA holder must submit the required patent information within 30 days of the issuance of the patent for it to be considered timely filed. If the NDA holder timely submits the required patent information, but FDA notifies the NDA holder that its Form FDA 3542 is incomplete or shows that the patent is not eligible for listing, the NDA holder must submit an acceptable Form FDA 3542 within 15 days of FDA’s notification to be considered timely filed as of the date of the original submission of patent information. New patent information may still be submitted after 30 days of the issuance of the patent, but such information is not considered timely filed.
Why Is Drug Patent Life Important?
Intellectual property laws protect drug manufacture and sales through patents. However, a large portion of a drug's patent life can expire due to research, development, and approval time before it ever hits the market.
Once they are marketed, however, drugs make a lot of money. They are depended upon by thousands or millions of people. If a patent for a best-selling drug runs out, other companies can begin engineering it. People will stop buying the original company product, costing that company a great deal of money.
When a company owns a patent to a drug, it is sold under a brand name. Doctors usually prescribe it using that name, which is a patented term for the ingredients in that drug. The company has a monopoly on it until its patent period ends (unless it attempts to extend or to renew it). The longer that drugs have their original patents, the longer before the companies making generic versions can manufacture those drugs to help make them more affordable.
How to extend life of patent
The Hatch-Waxman Act
This act was passed in 1984. Its chief purpose was to help balance out the many years a company can lose in patent life while it waits for the drug to be tested and certified. Extensions can be permitted in order to make up for this lost time, but there are a few exceptions. Firstly, the extension cannot go beyond five years, regardless of how many years the company lost while waiting. Secondly, the actual maximum amount of years for a company to own a patent once it's been approved is 14. Between these two numbers, there is not much flexibility.
Pediatric Exclusivity
By seeking to test out a drug on children, a patent can be extended for six months. This arrangement can occur two times with the same drug.
New Versions
One trick companies use is to combine the medical components in a somewhat new way by coming up with a newer concoction of what is essentially the same medicine. They might make a drug more tolerable via numerous new methods. For example, they might change a particular intake to a slow-release, or they might change from one daily dose to two, or transition from an oral medicine to an injection.
Transcept's Intermezzo is an example of alternative delivery. The pill form of the drug, Ambien, had been in use for several years. Intermezzo, which dissolves under the tongue, has a lower dosage of its active chemical as well as faster activation and a slightly different effect on the user. Therefore, it qualified for a five-year exclusivity period, which offset the expiration of the patent on Ambien.
New Things It Can Do
The FDA has a rule called the "three year new use" stipulation. It means that when it's discovered that the drug can achieve another remedy, you can increase the patent for three years on the basis of its new purpose.
Chemical Adjustments
Companies can make adjustments to the amount of isomers in a medicine. When companies do so, the drug is essentially different, even though it's achieving the same purpose. If one isomer doesn't add anything to the purpose, it can be deleted, and then it's a new drug, ready for an extended patent. Another term for this is "purification," meaning that when an unnecessary chemical is taken out of the combination, it leaves behind what really matters. Regardless, it's considered a new drug.
An example of purification is Lundbeck's Lexapro. It took only three-and-a-half years to develop because its predecessor, Celexa, used two forms of the molecule citalopram. Lexapro was considered a purified form because it utilized only the one of these forms that caused the anti-depressant effect. Because Lexapro didn't use the second form of the molecule, it was seen as a new drug, and the FDA granted the company a five-year exclusive period. This period corresponded to the expiration of Celexa's patent. Sometimes, as in this case, purifications offer fewer side effects.
New Combinations
Sometimes, it isn't dangerous to combine two drugs into one. In some cases, it may even to be found to be more effective. At least, it can have a neutral effect. Therefore, companies have been known to fuse two medications together, thereby coming up with a new drug for patenting. Likewise, two mechanisms can be considered for one medicine, and this may also extend patent life.
For example, Pfizer patented Caduet, a heart disease drug that included two of its other patented drugs, Norvasc and Lipitor. The patents for the underlying molecules of the earlier drugs expired, but because Pfizer had a patent on the combination, no other company could produce it.
Combination drugs sometimes increase consumers' co-pays or require full retail payment because they are new. In these cases, patients can request the separate drugs from their doctors.
Drugs for Rare Diseases
A rare disease is defined as one that fewer than 200,000 people in the U.S. have in any given year. In order to encourage drug companies to develop treatments for such diseases and to keep these medicines available, a seven-year patent extension is possible for these drugs.
30-Month FDA Stays
If a generic company applies for approval of a spoken-for patent in order to claim a right to it, then the FDA gets involved, and a conflict and potential court case can ensue. When this happens, the original company could receive as much as another 30 months of patent life, unless the case is settled sooner.
- Novartis v. Union of India (2013) 6 SCC 1 :-
Rejection of a patent for a Drug which was not ‘inventive’ or had an superior ‘efficacy’-
Novartis filled an application to patent one of its drugs called ‘Gleevec’ by covering it under the word invention mentioned in Section 3 of the Patents Act,1970. The Supreme Court rejected their application after a 7 year long battle by giving the following reasons: Firstly there was no invention of a new drug, as a mere discovery of an existing drug would not amount to invention. Secondly Supreme Court upheld the view that under Indian Patent Act for grant of pharmaceutical patents apart from proving the traditional tests of novelty, inventive step and application, there is a new test of enhanced therapeutic efficacy for claims that cover incremental changes to existing drugs which also Novartis’s drug did not qualify. This became a landmark judgment because the court looked beyond the technicalities and into the fact that the attempt of such companies to ‘evergreen’ their patents and making them inaccessible at nominal rates.
- Hoffmann-La Roche Ltd vs Cipla Ltd., Mumbai Central,:-
First Patent Litigation in India post India’s 2005 Product Patent Regime which included public interest and pricing issues.
Over the years India has seen many patent disputes between Foreign Multinational Pharmaceutical companies and Indian generic drug companies. But the suit between Roche and Cipla has surely set the standards when it comes to a patent infringement suit.
In this case, two plaintiffs, namely, F. Hoffmann-La Roche Ltd. and OSI Pharmaceuticals Inc., filed the suit for permanent injunction restraining infringement of patent, rendition of accounts, damages and delivery against Cipla Ltd. Mumbai. Indian Generic manufacturer Cipla won this landmark case in the Delhi High Court. The case is the first Patent Litigation in India post India’s 2005 Product Patent Regime which included public interest and pricing issues in addition to India’s Section 3d that prevents evergreening. The case was followed by Pharma Giants worldwide.
Roche sued Cipla in 2008 before Delhi High Court claiming that Cipla’s generic product Erlocip violates former’s Indian ‘774 patent claiming “Erlotinib Hydrocloride”. The trial Judge rejected Roche’s appeal to grant interim injunction restraining Cipla from selling generic version of Tarceva on the grounds of public interest and the fact that there was an ongoing patent revocation proceedings against ‘774 patent. Cipla’s generic version costs about 1/3rd of Roche’s patented drug. Roche’s subsequent appeal to Division Bench also failed when not only did the bench uphold the findings of Trial Judge but also imposed costs on Roche for suppression of material patent information about Roche’s later filed application in India (IN/PCT/2002/00507/DEL). This was the Patent Application which was actually on Polymorph Form B of Erlotinib Hydrocloride but was rejected in 2008 following the opposition filed by Cipla primarily on Section 3d. Cipla argued that Tarceva corresponds to Polymorphic Form B (which is not a product of ‘774 patent but a ‘507 rejected application) and that it is Form B which is more stable and suitable for solid oral dosage form than the compound disclosed in ‘774 patent comprising a mixture of Forms A and B. Roche’s subsequent appeal before the Supreme Court (SC) challenging the order passed by the division bench got dismissed due to the ongoing trial at the Delhi High Court.
