Lipitor patent expires, all eyes on Ranbaxy generic

For the Ranbaxy brass, the past week must have been the toughest in their career as they attempted to patch up with the drug regulator of United States to facilitate the exclusive launch of a low-cost version of Pfizer’s blockbuster drug Lipitor, after its patent protection expired on November 30, in the US.

An approval from the Food and Drugs Administration (FDA) was the only hurdle before Ranbaxy, the generic company that had successfully challenged Lipitor patent and secured a six-month exclusive right to sell the low-cost version of the $10.7-billion medicine in the US market after patent expiry, to monetise this opportunity.

Ranbaxy is expected to earn $600 million if it manages to sell the Lipitor generic, exclusively for six months.

Watson, the company other than Pfizer and Ranbaxy that can market a low-cost Lipitor by virtue of an agreement with Pfizer during the exclusivity period, announced the launch of its product on Wednesday. Unlike Ranbaxy, Watson did not require FDA approval, as the company was merely marketing the medicine produced and supplied by Pfizer.

Pfizer has also reduced the price of Lipitor to minimise the effect of the shift in prescriptions to the low-cost versions.

Ranbaxy’s ability for timely launch of this product came under doubt after two of its manufacturing facilities in India (one of which was to supply Lipitor generic) were placed under an export restriction in 2008 after the FDA raised some serious compliance issues. As a result, all new product approvals from these plants were put on hold and export of 30 drugs banned.

Now, it is the turn of Ranbaxy to secure approval and start shipping its version of Lipitor, the cheapest among the three, to the US market. Analysts expect the drug to fetch $600 million in six months, though the sheen of its profits may fade if the company pays a good portion of that as penalty to FDA to secure marketing approval.

The company had not announced the status of FDA approval till we went to press.

“Half of the revenues from Lipitor generic sales will be profit for Ranbaxy. However, it is a one-time opportunity and will not have a positive impact on the long-term performance of the company,” said Ranjit Kapadia, an analyst with Centrum Broking.

“Ranbaxy may miss a few days if the (FDA) approval comes late, but it will not impact the (six month) period of exclusivity, as its product exclusivity will kick in only from the day the company launches its product in the US,” said an industry expert, who did not wished to be named.

According to him, what will help Ranbaxy is the specific clause in the Medicare Modernisation Act (passed by the United States in 2003), which excludes all six-month exclusivity approvals gained before the enactment of the law from its stipulations. The MMA has detailed mention of the conditions under which a drug company may have to forfeit its six month marketing exclusivity if it fails to get necessary approvals on time. The Ranbaxy Lipitor challenge predates MMA.

Ranbaxy and its majority stake holder, Japanese drug major Daiichi Sankyo, had repeatedly expressed confidence over their ability to monetise the six month market exclusivity.

Ranbaxy’s approval status remaining a question, the industry was abuzz over the various marketing strategies the company might have looked at to minimise the loss of its exclusive marketing opportunity.

Daiichi Sankyo, in a recent communication, had stated Ranbaxy will start selling Lipitor generic in the US from November 30.

Earlier reports also had hinted that the company plans to manufacture the drug at its site in New Brunswick, New Jersey, US with raw materials sourced from approved sources.

Meanwhile, Pfizer hopes to hold on to the brand popularity by announcing patient friendly schemes to make consumers stick to their version of the drug even after the introduction of a low-cost variant.

The company has also, as noted earlier, authorised US-based generic drug maker Watson Pharmaceuticals to sell the “authorised generic” of Lipitor after patent expiry. US laws permit the patent holder to allow one such “authorised generic” to be marketed during the six-month exclusivity period.

Update 1:Patent enforceability US Case (Temodar)

CAFC reversed district court's findings on patent enforceability of 5,260,291 (assigned to schering)

(CAFC decision)

I have already blogged on this (Link 1) (Link 2) 

News today: Settlement & Litigations

1) Sanofi settlement with generic drug companies - Oxaplatin [Link]

2) Eli Lilly - Gemcitabine district court decision; Product patent (4808614) held valid and MOT patent (5464826) held invalid [Link]

3) In case between Teva/Duramed Vs Watson, District court of Nevada granted Teva summary judgement on validity of patent [7,320,969] pertaining to Seasonique (Women contraceptive: Levonorgestrol and ethinyl estradiol) [Link]

Update:Patent enforceability US Case (Temodar)

Teva, in press release, said that the parties to the patent litigation of Barr vs Schering related to Temodar [temozolomide] have entered into an agreement pending resolution of Schering’s appeal to the Federal Circuit of the U.S. District Court’s decision holding the ‘291 Patent unenforceable.

Under the terms of the agreement, subject to limited exceptions, Teva will only market a generic product should the Federal Circuit uphold the District Court’s decision. Furthermore, the agreement grants Teva the right to commence selling its generic product as of August 2013, during the period of Schering’s pediatric exclusivity.

Earlier Post [Link]

Patent enforceability US Case [CRCT Vs Barr]

Temodar [temozolomide] is marketed by Merck/Schering and is used for treatment of brain cancer [glioblastoma multiforme and refractory anaplastic astrocytoma]. Barr Pharma had filed ANDA seeking approval to market generic version of temozolomide. As the product patent has not expired and listed in Orange book, Barr has filed ANDA with PIV certification on product patent.

Product patent details

Patent No: US 5,260,291; Assignee: Cancer Research technology UK Ltd

Title: Tetrazine derivatives

US Expiry date: Aug 11, 2013

Patent claims original priority of first application filing date: 23/08/1982 and patent term extended around 3 years

Merck Schering is exclusive licensee of this patent ['291]

Upon filing ANDA with PIV certification on product patent, CRT has sued Barr (Teva) and consequently ANDA approval stayed for 30 months. In complaint, CRT argued that Barr's ANDA will infringe claims '291 patent. In answers, Barr has raised enforceability of '291 patent.

Defendant argument on Patent unenforceability

1) Doctrine of prosecution laches: This patent application's prosecution involves 11 patent application and 10 abandonment is unreasonable delay and no substantive prosecution for decades.

2) Inequitable conduct: Applicant was in possession of Human clinical trial data during the patent application prosecution and withheld from PTO

Court agrees on both arguments of defender by analyzing various facts and evidences submitted during trial.

Merck will appeal this decision

Links

[Teva Press release] [Merck press release] [District court decision]

Erlotinib Indian Case

Erlotinib Case Summary

Erlotinib is marketed by OSI Pharma in US and by Roche in non US areas.

Pre grant opposition of product patent 537/DEL/1996

[Natco Vs Pfizer]

Erlotinib infringement case:

Erlotinib product patent is granted in India [Patent No:IN196774, Application No:537/DEL/1996] equivalent to US 5747498. Cipla announced launch of generic version of Tarceva [Erlotinib]. Roche sued Cipla in Delhi High court for infringement of product patent ['774] and to grant injunction to market cipla product.

Injunction was denied to Roche

[Lower Bench; Ravinder Bhatt decision] [Appeal Higher bench; S. Muralitharan]

Pre grant oppositions of Polymorph related patents

OSI has filed to two patent applications, which are equivalent to US 6900221

IN/PCT/2002/507/DEL [Cipla Vs OSI] granted as ??

IN/PCT/2002/497/DEL [Cipla Vs OSI] granted as ??

Power Plants for Liver Diseases

1. Karisalankanni:

Botanical Name: Eclipta prostrata
Used for treatment of:
 Liver disease (herb of choice for liver diseases)
 Ulcer
 Jaundice
 Fatty liver
 Splenomegaly
 Hemorrhoids and
 Indigestion

Source: http://ayurvedichomeremedies.blogspot.com/2007/11/liver-and-ayurveda.html

2. Kizhanelli:

Botanical Name: Phyllanthus Nruri
Family: Euphorliaceae
Hindi: Buin anvalah, Jar – amla
Telugu: Nelavusari
Tamil: Kizha Nelli, Kizkhai Nelli, Kilkkay nelli, Kizvai nelli
Used for treatment of:
 Jaundice
 Gonorrhea
 Urinary tract
 Frequent menstruation
 Dysentery
 Diabetes
 hepatitis B
 Also antifungal, antiviral, and anticancerous properties

Source: http://ayurvedham.com/english/tag/keezhanelli

NDA and BLA approvals by US FDA – November 2009

1. Only one New molecular entity (NME) has been approved by FDA in this month.
 Drug Name: ISTODAX
 Company: Gloucester Pharms
 Active ingredient: ROMIDEPSIN
 Review Class: Standard review drug

2. Four new formulations has been approved as shown below:
 Drug Name: LYSTEDA
 Company: Xanodyne Pharm
 Active ingredient: TRANEXAMIC ACID
 Review Class: Priority review drug

 Drug Name: NEXCEDE
 Company: Novartis
 Active ingredient: KETOPROFEN
 Review Class: Standard review drug

 Drug Name: REVATIO
 Company: Pfizer
 Active ingredient: SILDENAFIL CITRATE
 Review Class: Standard review drug

 Drug Name: PENNSAID
 Company: Nuvo Res
 Active ingredient: DICLOFENAC SODIUM
 Review Class: Standard review drug

3. One drug which is already in market (with out approval from FDA) for approved.
 Drug Name: QUTENZA
 Company: Neurogesx
 Active ingredient: CAPSAICIN
 Review Class: Standard review drug

4. A drug with out any NDA chemical type classification is also approved by US FDA
 Drug Name: KALBITOR
 Company: Dyax Corp
 Active ingredient: ECALLANTIDE
 Review Class: Unspecified

Generic Drug Approvals by FDA - November 2009

A quick view on the Generic drug approvals by US FDA this month (Nov'09).

1. Akorn Inc and Alcon Inc has obtained two generic drug approvals this year for KETOROLAC TROMETHAMINE OPHTHALMIC SOLUTION (0.4%, 0.5%); Notably, Apotex Inc and Sun Pharma has obtained one approval each (0.4%, 0.5% respectively) for the same drug.

2. One of the generic drug competitor, Barr Laboratories have got an approval on NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL TABLETS (1 MG/0.005 MG)

3. Another generic drug competitor, Teva Pharmaceuticals and Matrix laboratories have obtained approval for LANSOPRAZOLE DELAYED-RELEASE CAPSULES (15 MG and 30 MG)

4. The Indian pharma company, Aurobindo Pharma and Roxane laboratories, Ivax Pharmaceuticals (a subsidiary of Teva) have got nod for PERINDOPRIL ERBUMINE TABLETS (2 MG, 4 MG and 8 MG)

5. Par pharmaceuticals got approval for TRAMADOL HYDROCHLORIDE EXTENDED-RELEASE TABLETS (100 MG and 200 MG)    

6. The drug, NICARDIPINE HYDROCHLORIDE INJECTION (2.5 MG/ML; PACKAGED IN 25 MG/10 ML) was approved for Generamedix Inc, Pharmaforce Inc, Vavinta LLC, Sun pharma and Wockhardt Ltd.

7. NIZATIDINE ORAL SOLUTION (15 MG/ML) was approved to Amneal Pharmaceuticals.

Patent, Patenting and business

Patents are the concept which was originated to protect the investment made to make inventive, novel and not known technical development for benefiting people and/or society. This is an agreement between government and inventor (Or assignee) to grant exclusive rights for bring developed, novel benefiting innovation to people and to protect your money investment made to make such innovation. The granted rights are like physical property, could be sold to anyone. This patent right is valid to limited time duration (Normally 20 years). Patents enhance industrial growth by protecting huge money involved in research and development.

Patents and their governing laws are very different from country to country, since each country has their own way of interpreting and also depends countries' industrial growth and requirement. Before 2005, India have not had granted product patent for pharmaceutical/agrochemical innovations, to protect India's generic industry.

In the name of globalization, to protect foreign investments and exploring new markets, many international agreements and co-operations, were established

1) Paris conventions

2)Patent cooperation treaty (by WIPO; UN)

3) TRIPS (by WTO; UN)

4) Regional treaty like

European patent convention (EPC), Eurasian patent organization (EAPO), The cooperation council for the arab states of the Gulf (GCC), African regional intellectual property organization (ARIPO), African intellectual property organization (OAPI).

TRIPS agreement is major break through to bring minimum standards in countries' patent/IP and related laws to enhance international business activities in unexplored big markets like many asian countries, africa, latin america and like.

New Developments are

1) patent prosecution highway (PPH) cooperation between large volume patent offices to prevent repeated work

2) Community patent for European union (enhanced version for EPC)

3) IP5 (joined project by major 5 IP offices)

Disclaimer:

there may be some errors since these are my personal views on patent and related law