Esomeprazole Magnesium (Nexium): Innovator AstraZeneca sued Sandoz

Innovator AstraZeneca has sued another generic player over Esomeprazole Magnesium ER 20 and 40 mg capsules patents. Innovator has filed an infringement suit against Sandoz in New Jersey District Court for to protect its monopoly over the blockbuster medication after Sandoz filed ANDA with Para IV certification against Orange Book listed patents for Esomeprazole magnesium capsules.
Innovator has alleged Infringement of following patents in the complaint:
US5714504 (Expiry: Aug 3, 2015): which covers a pharmaceutical formulation for oral administration comprising a pure solid state alkaline salt of the (-)-enantiomer of 5-methoxy-2[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzi midazole and a pharmaceutically acceptable carrier.
US5877192 (Expiry: Nov 27, 2014) : which covers a method for treatment of gastric acid related diseases by inhibition of gastric acid secretion comprising administering to a mammal in need of treatment a therapeutically effective amount of a proton pump inhibitor consisting essentially of the (-)-enantiomer of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benz imidazole or a pharmaceutically acceptable salt thereof, so as to effect decreased interindividual variation in plasma levels (AUC) during treatment of gastric acid related diseases.
US6875872 (Expiry: Nov 27, 2014): which covers a Magnesium salt of (-)-5-methoxy-2-[[(4-methoxy-3,5,dimethyl-2-pyridinyl)methyl]sulfinyl]-1H- benzimidazole in an optical purity of at least about 94% enantiomeric excess.
US6369085 (Expiry: Nov 25, 2018): which covers a the magnesium salt of S-omeprazole trihydrate, with XRD and process of manugacturing the same
US7411070 (Expiry: Nov 25, 2018): which covers a the magnesium salt of S-omeprazole trihydrate.
Innovator is already in litigation with IVAX Corporation, Zenith, Teva and Dr. Reddy's for this product in New Jersey court. Earlier in April 2008, Innovator announced patent settlement with first Para IV filer Ranbaxy. As per settlement agreement, Ranbaxy will commence sales of a generic version of Nexium under a licence from AstraZeneca on May 27, 2014 onwards.

AstraZeneca initiated infringement suit against generic S-omeprazole of DRL

AstraZeneca Has filed a lawsuit against Dr. Reddy's Laboratories For the Infringement of US 5,714,504 (which covers composition), US6,875,872 (which covers Compounds,), and US6,369,085 (which covers Form of S-omeprazole) following a paragraph IV certification as part of DRL's filing of an ANDA to manufacture a generic version of AstraZeneca's Nexium® .In a complaint filed Thursday in the U.S. District Court for the District of New Jersey, AstraZeneca alleged that the Indian generic maker’s ANDA to the USFDA for 20 mg and 40 mg delayed release esomeprazole magnesium caplets infringes its Nexium patents.According to AstraZeneca’s complaint, Dr. Reddy’s ANDA seeks to market its esomeprazole magnesium products before the expiration of AstraZeneca’s patents, US5714504; US6875872 and US6369085, thus infringing the patents.AstraZeneca claims that Dr. Reddy’s is required to submit to the FDA specific reasons why its generic product will not infringe AstraZeneca's patents. Dr. Reddy’s has failed to meet this requirement, the complaint said.In December, AstraZeneca asked Dr. Reddy’s to supply more information and samples of its generic product so that the drug maker could determine whether the proposed product would infringe its patents.“DRL refused to agree to timely provide AstraZeneca sufficient access to all of the requested documents, information and samples and instead offered to produce only selected portions of DRL’s ANDA Number 78-279 and certain finished product samples,” the complaint said.AstraZeneca filed the suit in part “to employ the judicial process and the aid of discovery” to determine whether Dr. Reddy's proposed generic esomeprazole magnesium will infringe its three patents, according to the complaint.AstraZeneca is seeking a permanent injunction barring Dr. Reddy’s from marketing an infringing product, court costs and attorneys’ fees.In November 2005, the company asserted the three patents and others against a slew of generic makers, including Ranbaxy Pharmaceuticals Inc., Ivax Corp. and Teva Pharmaceuticals Industries Ltd. That case is still pending the New Jersey District Court.AstraZeneca also faced challenges to Nexium from competitors in Europe. But in November, the European Patent Office reportedly ruled that a patent covering Nexium was still valid in its amended form despite challenges from four generic competitors.In December 2006, the EPO said it had revoked the substance-of-matter patent, which was not set to expire until 2014, following an appeal from Ratiopharm.Nexium is a slightly revised form of Prilosec, another AstraZeneca blockbuster heartburn drug. It is also one of the world’s top-selling drugs, with global sales of $2.62 billion in the first half of 2007.

Esomeprazole (Nexium): AstraZeneca faces early generic in Denmark

Innovator AstraZeneca's blockbuster stomach ulcer and acid reflux molecule Esomeprazole magnesium (Nexium) faces early generic competition in Denmark, where Sandoz launched a generic version this week.

An AstraZeneca spokesman said on Thursday the group was aware of the launch, adding that authorisations for generic forms of the medicine had also been granted in Ireland, Portugal, Austria, Hungary, Estonia, Latvia, Lithuania, Finland and Slovenia.

In major European countries, however, the product is still protected by market exclusivity that only expires in March 2010. (Source: Reuters article Here )

Further, generic players have opposed key patents of innovator in EU market like EP00652872 (revoked by EPO) and EP00773940.

In US market, innovator has fared well and was successful in blocking generic challenge. Generic players like Sandoz, Dr. Reddy and Ivax challenged innovator but have not succeded till date. Also, the first para IV filer Ranbaxy settled patent litigation with innovator and would be able to launch generic version under licencing agreement from May, 2014 onwards. Innovator Astra has strong patent portfolio for this product.

Earlier news of Ippharmadoc on this product Here

Race to takeover: Innovator to generic and generic to bigger generic; Teva to buy Barr pahrma?

In last few days a paradigm shift is being observed in Pharmaceutical industry. Innovator companies are turning to generic buissness. The recent exmple of Daiichi Sankyo aquiring Ranbaxy to enter into the generic market. Also, another innovator company Sanofi Aventis is making a bid to acquire Czech generics company Zentiva.
Generic to bigger generic
Also, some generic companies are aquiring other generic companies like Sun pharma trying to buy Taro. Teva in a bid to aquire generic firms have paid $400 million to buy CoGenesys and is expected to close soon on a deal to purchase Bentley Pharmaceuticals for about $350 million. Now a Israel news paper has speculated here that Teva will buy Barr Pharma for about 7-7.5 $ billion

Innovator to generic trend was started by Novartis by floating its generic unit Sandoz. Now many innovator companies are eyeing this strategy. The Reason for this U turn seems to be due to following factors:


1) Loss of innovation: Drug development is a very risky affair which can consume billion dollars. All the latest techniques of drug development have not led to a blockbuster drugs. In nutshell, the innovation pipeline has dried up. Although, research is going on but these companies know that its difficult to launch a drug in 2-5 yr time, to cover up that gap and fund research generic buissness is ideal choice


2) Off-patent Scenario: After the expiry of key patent of innovator, its difficult to sustain in competion with generic players. The market for innovator product after generic launch erode very quickly.


3) High cost of drug development: With drug intermediate and other raw material prices zooming, the new drug development has became more expensive. Further, clainical trials ae also becoming more expensive.

4) Thriving generic companies: Some of the generic companies have achieved sales equivalent to innovator. The innovator mostly get 5 yr exclusivity and sales normally rises yearwise. By the end of 4th year of exclusivity, generic companies are ready with their strategy and file dossier to challenge innovator. As in US First para IV filer got 180 days exclusivity, so if a generic player enter after the end of innovator's 5 yr exclusivity they got profit in the tune of millions (Some times sales achieved by innovator in first 3 years of exclusivity). Further, the risk and money involved for generic companies for development and launch is minimal.

5) Pro generic patent laws: The patent laws in US and EU are becoming more favorable to generic companies. The KSR V.s Teleflex decision which changed the obviousness concept is proving detrimental to product patents in US. Recent example for this are Pramipexole and Ramipril, whose product patent was invalidated by Us court. Recently, in Europe the product patent of Esomeprazole got invalidated.

6) Failure on Patent evergreening: Generic companies in the last 8 years have devloped their skills to stop patent evergreening attempts of innovator. Earlier, innovator in an attempt of evergreening of patent would get patents on polymorph, salt, formulation, purity, hausner ratio, bulk density, method of use, new combination etc. to thwart generic challenge. But all these patent are not sufficient to stop generic challenge once molecule or product patent expires.

Prilosec and Nexium Find No Evidence of adverse cardiovascular effects

AstraZeneca, the maker of Prilosec (omeprazole) and Nexium (esomeprazole), sent FDA data from two long-term studies in patients with severe gastroesophageal reflux disease (GERD) that were being treated with either Prilosec or Nexium. The studies were designed to assess the effectiveness of treatment with Prilosec, or Nexium, or surgery for severe GERD. Participants were randomly assigned to receive treatment with either a drug (Prilosec in one study and Nexium in the other) or surgery. During the studies, cardiovascular events raised a question about whether long-term use of these drugs increases the risk of heart attacks, heart failure, and heart-related sudden death in patients taking either one of the prescribed drugs compared to patients who received surgical treatment. On Aug. 9, 2007 FDA released an "Early Communication of an Ongoing Safety Review" of these drugs. The agency’s initial review determined that there was no increased risk of heart problems associated with long-term use of these drugs. At FDA’s request, AstraZeneca submitted a large amount of additional information about these and other studies and FDA undertook a comprehensive review of all available data regarding this potential safety concern.

Esomeprazole Magnesium (Nexium) 20 and 40 mg tablets: Innovator Astra settled patent litigation with Teva

Innovator Astra settled patent litigation with Teva pending in the U.S. District Court for the District of New Jersey

After first settling with first paara IV filer Ranabxy in April, 2008, innovator M/S AstraZeneca has entered into a licensing agreement with generic player Teva and as per terms of the settlement Teva would be able to launch the generic version in May 27, 2014 (after the expiry of two key Orange Book listed patents US5877192 and US6875872), onwards.

Teva has admitted the validity of following Orange Book patents:

US5,690,960

US5,714,504

US5,877,192

US5,900,424

US5,948,789

US6,428,810

US6,369,085

US6,875,872

US7,411,070

The other generic players like Sandoz, Dr. Reddy's and Lupin are in patent litigation with innovator, the litigation is pending in New Jersey District Court.

Esomeprazole (Nexium):Ranbaxy settled lawsuit with innovator

AstraZeneca announced that it has settled a lawsuit against Indian pharma giant Ranbaxy Lab in an agreement that will keep Ranbaxy's generic version of the blockbuster heartburn drug Nexium off the U.S. market until 2014.
AstraZeneca also awarded Ranbaxy some valuable contracts, which are separate from the litigation settlement. These contracts could trigger questions from the U.S. Federal Trade Commission, which still must review the agreements. The commission has objected to some deals where it believed that a patent holder was giving a generic company something of value in exchange for staying off the market, arguing that this process decrease competition and hurt consumers.
The agreement settles the patent infringement litigation filed by AstraZeneca following Ranbaxy’s submission to the USFDA an ANDA for a generic version of Nexium. Under the settlement agreement, Ranbaxy concedes that all six patents asserted by AstraZeneca in the patent litigation are valid and enforceable. Ranbaxy also accepts that four of the patents would be infringed by the unlicensed sale of Ranbaxy’s proposed generic product.The settlement agreement will allow Ranbaxy to commence sales of a generic version of Nexium under a licence from AstraZeneca on 27 May 2014. This date marks the expiry of US5877192 and US6875872. AstraZeneca’s patents protecting Nexium have expiration dates that range from 2014 through 2019.AstraZeneca and Ranbaxy have filed a Consent Judgment with the US District of New Jersey reflecting the terms of the settlement agreement. With the Court now having entered the Consent Judgment, the settlement agreement is final, and the patent infringement litigation against Ranbaxy has been dismissed.Nexium had U.S. sales of $5.5 billion last year, making it the second-biggest-selling drug, behind Pfizer Inc.'s cholesterol pill Lipitor, according to IMS Health.
In contracts AstraZeneca said were separate from the settlement, the company is allowing Ranbaxy to start making a portion of AstraZeneca's Nexium supply in May 2010. Ranbaxy will also start supplying AstraZeneca with the active pharmaceutical ingredient used to make Nexium in May 2009.
AstraZeneca is also giving Ranbaxy the right to distribute generic versions of two older AstraZeneca drugs -- Plendil for hypertension and Prilosec for heartburn -- in the U.S.
AstraZeneca still faces battles with other makers of generic drugs that are attempting to sell copies of Nexium as well as the company's drug to treat schizophrenia, Seroquel, in the U.S.
As per FDA guidelines Ranbaxy could have started selling generic Nexium this week, when a 30-month stay barring Ranbaxy from the market expired. But if Ranbaxy had started selling generic Nexium but lost the litigation, it would have to pay willful infringement damages to Astra.

Innovator in generic business: Pfizer announced licensing agreement with Aurbindo pharma to expand generic portfolio

Pfizer has agreed to license generic solid oral dosage forms and injectable medicines from India's Aurobindo Pharma Ltd to commercialize medicines that are no longer patent protected and have lost market exclusivity in the regulated market .

In the deal announced on Tuesday, Pfizer said it expected the products acquired to deliver more than $200 million in near future, according to David Simmons, general manager of Pfizer's established products business unit.
The products expand Pfizer's growing generics portfolio and are versions of drugs originally made by companies other than Pfizer. Financial terms of the deal were not disclosed.
Pfizer's Greenstone subsidiary already sells above 300 Pfizer medicines that have lost patent protection but still brought in a combined $10 billion last year. As per press release, Pfizer expects major revenue from generic business in 2013.

The licensing agreement with Aurbindo for generics can be attributed to patent expiry of blockbuster formulation of Pfizer like Atorvastatin, Sildenafil citrate, Celecoxcib, Pregabalin and Voriconazole etc. in near future. Pfizer is focusing on off-patent medicines as one avenue to spur profits as the drugmaker encounters generic competition that threatens revenue of its own top sellers.

Eralier, Pfizer acquired some major innovator companies like Warner-Lambert / Parke-Davis / Agouron, Pharmacia / Upjohn / Searle, SUGEN. Recently, Pfizer acquired Wyeth and Bayer to further strengthen its innovation approach.

Innovator companies are nowadays switching over to generic business after patent expiry of their blockbuster drugs. The trend was started by Novartis which opened it’s successful generic unit Sandoz, later on other innovator companies like Daiichi (Ranbaxy), Sanofi Aventis (Zentiva) entered into generic business.

Following are some factors for innovator companies interest in generic business:

1) Loss of innovation: Drug development is a very risky affair which can consume billion dollars. All the latest techniques of drug development have not led to a blockbuster drugs. In nutshell, the innovation pipeline has dried up. Although, research is going on but these companies know that its difficult to launch a drug in 2-5 yr time, to cover up that gap and fund research generic buissness is ideal choice

2) Off-patent Scenario: After the expiry of key patent of innovator, its difficult to sustain in competion with generic players. The market for innovator product after generic launch erode very quickly.

3) High cost of drug development: With drug intermediate and other raw material prices zooming, the new drug development has became more expensive. Further, clainical trials ae also becoming more expensive.

4) Thriving generic companies: Some of the generic companies have achieved sales equivalent to innovator. The innovator mostly get 5 yr exclusivity and sales normally rises yearwise. By the end of 4th year of exclusivity, generic companies are ready with their strategy and file dossier to challenge innovator. As in US First para IV filer got 180 days exclusivity, so if a generic player enter after the end of innovator's 5 yr exclusivity they got profit in the tune of millions (Some times sales achieved by innovator in first 3 years of exclusivity). Further, the risk and money involved for generic companies for development and launch is minimal.

5) Pro generic patent laws: The patent laws in US and EU are becoming more favorable to generic companies. The KSR V.s Teleflex decision which changed the obviousness concept is proving detrimental to product patents in US. Recent example for this are Pramipexole and Ramipril, whose product patent was invalidated by Us court. Recently, in Europe the product patent of Esomeprazole got invalidated.
6) Failure on Patent evergreening: Generic companies in the last 8 years have devloped their skills to stop patent evergreening attempts of innovator. Earlier, innovator in an attempt of evergreening of patent would get patents on polymorph, salt, formulation, purity, hausner ratio, bulk density, method of use, new combination etc. to thwart generic challenge. But all these patent are not sufficient to stop generic challenge once molecule or product patent expires.