Divalproex sodium: Nupharm V/S FDA

Fdalawblog has published a very interesting article on Divalproex sodium delayed-release 500 mg tablets

Earlier this month, we reported on a complaint filed by Nu-Pharm Inc. against FDA in the U.S. District Court for the District of Columbia seeking declaratory and injunctive relief with respect to the company’s Abbreviated New Drug Application ("ANDA") #77-615 for generic divalproex sodium delayed-release 500 mg tablets. Divalproex sodium delayed-release 500 mg tablets is marketed by Abbott Laboratories under the trade name DEPAKOTE. Nu-Pharm’s ANDA contained a paragraph IV certification to the Orange Book-listed patents for DEPAKOTE, Abbott sued within the statutory 45-day period, and the 30-month stay triggered by the suit reportedly expired in November 2007. Late last week, the court dismissed the complaint in a one-page order.According to Nu-Pharm’s memorandum in support of a temporary restraining order and/or preliminary injunction, FDA must approve ANDA #77-615 because the company satisfied all requirements for final ANDA approval and the 30-month stay of approval triggered by the submission of Nu-Pharm’s ANDA with a paragraph IV patent certification expired without a substantive ruling on patent validity or infringement. FDA nevertheless refused to approve ANDA #77-615 based on an order entered in a contempt proceeding by the U.S. District Court for the Northern District of Illinois (Eastern Division) (Judge Richard Posner sitting by designation) involving an ANDA with a paragraph IV patent certification for generic DEPAKOTE submitted by Apotex Inc. (which formerly owned Nu-Pharm) that also extended to Nu-Pharm’s product.In October 2007, the U.S. Court of Appeals for the Federal Circuit reversed the district court’s contempt judgment in the Apotex case with respect to Apotex acting in concert with Nu-Pharm to submit an ANDA "because the district court erred in finding Apotex in contempt when the conduct at issue was not within the express terms of the injunction." The Federal Circuit also held, however, that the contempt procedure used by the Illinois court was proper, that Nu-Pharm’s divalproex sodium drug product was not colorably different from Apotex’s divalproex sodium drug product, and that Nu-Pharm’s product would infringe patents covering DEPAKOTE. Apotex’s request for the Federal Circuit to hear the case en banc was denied, and in January 2008, the company petitioned the Supreme Court for review.Nu-Pharm contends that notwithstanding the order in the Illinois court contempt proceeding –to which Nu-Pharm was not and is not a party- FDA is required to approve ANDA #77-615 under the plain language of FDC Act § 505(j)(5)(B)(iii), which states, in relevant part:If the applicant made a [paragraph IV certification], the approval shall be made effective immediately unless, before the expiration of 45 days after the date on which the notice described in [FDC Act § 505(j)(2)(B)] is received, an action is brought for infringement of the patent that is the subject of the certification and for which information was submitted to the Secretary under FDC Act § 505(b)(1) or § 505(c)(2)] before the date on which the application (excluding an amendment or supplement to the application), which the Secretary later determines to be substantially complete, was submitted. If such an action is brought before the expiration of such days, the approval shall be made effective upon the expiration of the thirty-month period beginning on the date of the receipt of the notice provided under [FDC Act § 505(j)(2)(B)(i)] or such shorter or longer period as the court may order because either party to the action failed to reasonably cooperate in expediting the action, except that . . .(II) if before the expiration of such period the district court decides that the patent has been infringed . . . .Specifically, Nu-Pharm argues, among other things, that "for purposes of ANDA approval, the only action that matters is the one brought against the particular ANDA applicant within the 45-day period for infringement of the patent that is the subject of the applicant’s paragraph IV certification."FDA, in the Agency’s memorandum accompanying its motion to dismiss, comments in response to Nu-Pharm’s statutory plain meaning arguments that:FDA must give effect to the [Illinois] court’s order, which expressly pertains to Nu-Pharm. . . . While Nu-Pharm is correct that FDA must ordinarily approve an otherwise approvable ANDA upon expiration of a 30-month stay, in this case, FDA is subject to a direct court order requiring FDA to delay the approval of Nu-Pharm’s ANDA until after January 29, 2008. Thus, Nu-Pharm’s statutory arguments miss the point entirely because Nu-Pharm fails to recognize (at least before this Court) FDA’s obligation to give effect to the Illinois court’s order. For this reason, Nu-Pharm’s lengthy statutory arguments are irrelevant.FDA goes on to cite two cases in which courts have rejected arguments that FDA’s decision to follow court orders were improper because they were inconsistent with the FDC Act.Although Nu-Pharm was unsuccessful in convincing the U.S. District Court for the District of Columbia to grant declaratory and injunctive relief, the company has expressed its intent to appeal the decision. Specifically, in Nu-Pharm’s brief, the company states:[I]n the event the Court denies Nu-Pharm’s request for emergency injunctive relief, Nu-Pharm respectfully requests that any adverse FDA decision be stayed and that Nu-Pharm’s 500 mg product be finally approved pending review by, and appeal of this matter to, the United States Court of Appeals for the D.C. Circuit

Pentoprazole News

The fight on genric pentoprazole has started and generic players Teva, Sun Pharma, Caraco and innovator Wyeth has released following press releases
Sun Pharma launched Pentoprazole in USA
Sun Pharmaceutical Industries Ltd. announced today that it has commercially launched generic Pantoprazole Sodium Delayed Release (DR) Tablets, 40 mg, which is AB-rated to Wyeth's Protonix® DR Tablets. Sun's product is being sold in the United States by its marketing partner Caraco Pharmaceutical Laboratories. Sun Pharma had received a USFDA approval for these tablets in Sep 2007. This strength of Pantoprazole Sodium has annual sales of approximately USD 2.3 billion in the US.Sun's launch was initiated after the December 22, 2007 commercial launch by Teva Pharmaceutical Industries Ltd. of generic Pantoprazole Sodium tablet products, and after the January 29, 2008 commercial launch by Wyeth of generic Pantoprazole Sodium tablets product through its designated distributor.Sun shares a 180-day period of marketing exclusivity with Teva for this product. Sun is currently involved in patent litigation with Wyeth and Altana (now Nycomed) concerning this product in the U.S. District Court for the District of New Jersey. Although no trial date has yet been set, in September 2007, the District Court denied a motion filed by Wyeth and Altana for a preliminary injunction related to Sun's Pantoprazole Tablets. Wyeth and Altana have appealed the District Court's decision.

Caraco to market Sun Pharma Pentoprazole
Caraco Pharma announced today that it has launched Pantoprazole Sodium Delayed-Release Tablets, 40 mg (Pantoprazole Sodium DR), which is AB-rated to Wyeth's Protonix(R) DR Tablets, on behalf of Sun Pharmaceutical Industries, Ltd. (Sun Pharma). Sun Pharma recently received approval from the US Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for generic Protonix(R), and being one of the first-to-file an ANDA with a Paragraph IV certification, shares a 180-day marketing exclusivity with Teva Pharmaceutical Industries Ltd.Caraco's launch on behalf of Sun Pharma was initiated after the December 22, 2007 launch by Teva Pharmaceutical Industries Ltd. of generic Pantoprazole Sodium DR tablet products, and after the January 29, 2008 launch by Wyeth of generic Pantoprazole Sodium DR tablets product through its designated distributor.Sun Pharma is currently involved in patent litigation with Wyeth and Altana (recently acquired by Nycomed) concerning this product in the U.S. District Court for the District of New Jersey. Although no trial date has yet been set, in September 2007, the District Court denied a motion filed by Wyeth and Altana for a preliminary injunction related to Sun's Pantoprazole Tablets. Wyeth and Altana have appealed the District Court's decision.Pantoprazole Sodium DR is indicated for the short-term treatment (up to eight weeks) in the healing and symptomatic relief of erosive esophagitis, is indicated for the maintenance of healing erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in patients with gastroesophageal reflux disease (GERD), and is indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger- Ellison syndrome. This new product is bioequivalent to Protonix(R), a registered trademark of Wyeth Pharmaceuticals Inc. Protonix(R) 40 mg tablets had U.S. sales of approximately $2.3 billion for the 12-month period ended September 30, 2007, according to IMS Data.Detroit-based Caraco Pharmaceutical Laboratories, Ltd., develops, manufactures, markets and distributes generic and private-label pharmaceuticals to the nation's largest wholesalers, distributors, drugstore chains and managed care providers.

Prasco to distribute authorized generic Pentoprazole

Wyeth and its business partner, Nycomed, today announced the U.S. launch of Wyeth's own generic version of PROTONIX(R) tablets, in response to the at-risk launch of generic pantoprazole tablets in the U.S. by Teva Pharma, on December 21, 2007. Wyeth's own generic version of PROTONIX will be distributed by Prasco starting today."Compound patents, like that infringed by Teva, represent the foundation of pharmaceutical innovation, a critical underpinning in bringing important new medicines to patients," says Bernard Poussot, President and Chief Executive Officer for Wyeth. "We believe the PROTONIX compound patent is strong and we will vigorously pursue our litigation against Teva and other infringing generics. Going forward, we will continue to seek an injunction against any infringement of this patent, as well as monetary damages, including lost profits, from Teva."Wyeth and Altana Pharma AG (recently acquired by Nycomed) sued Teva and Sun Pharmaceuticals for patent infringement based on Teva's and Sun's filing of Abbreviated New Drug Applications (ANDAs) seeking U.S. Food and Drug Administration (FDA) approval to market generic versions of PROTONIX before the patent expires on July 19, 2010. Under the Hatch-Waxman Act, the filing of the lawsuit stayed final FDA approval of Teva's ANDA until August 2, 2007, and Sun's ANDA until September 8, 2007. On September 6, 2007, The United States District Court for the District of New Jersey denied Wyeth's and Nycomed's motion for preliminary injunction. The Court did not rule on the validity of the patent, but rather concluded that, based on the limited record before it, Wyeth and Nycomed were not entitled to the extraordinary relief of a preliminary injunction. Trial is expected in the second half of 2008.
Prasco announced today that, pursuant to an agreement it entered into with the ESI Lederle Division of Wyeth ("ESI"), it is shipping the generic version of PROTONIX(R) (Pantoprazole Sodium) Delayed-Release Tablets being offered for sale by ESI. Prasco, as ESI's agent and on ESI's behalf, will solicit orders for and distribute the 20 mg and 40 mg formulations of Pantoprazole Sodium Delayed-Release (DR) Tablets to all trade classes in the U.S. under the ESI Lederle label. Pantoprazole Sodium DR Tablets are AB-rated, therapeutically equivalent and substitutable for the brand PROTONIX Delayed-Release (DR) Tablets."We are extremely pleased to have established this agreement with Wyeth, a global leader in the pharmaceutical industry," said Prasco Chief Executive Officer E. Thomas Arington. "Pantoprazole Sodium DR Tablets are identical to PROTONIX DR Tablets, providing the consuming marketplace the benefits of competitive balance and brand-quality at generic prices," stated Arington.PROTONIX DR Tablets had reported sales of $2.5 billion dollars in the United States, with over 19 million prescriptions filled for the twelve months ended November 30, 2007, based on IMS sales data. PROTONIX is a registered trademark of Wyeth Pharmaceuticals, Inc.

Teva announced termination of agreement with Wyeth
Teva Pharma announced today that the Company's standstill agreement with Wyeth/Altana regarding additional shipments by Teva of generic Protonix (Pantoprazole Sodium) has terminated as a result of Wyeth's launch of an authorized generic product.Teva is currently involved in patent litigation with Wyeth/Altana concerning this product in the U.S. District Court for the District of New Jersey. A trial date has not been set.In September 2007, the District Court denied a motion filed by Wyeth/Altana for a preliminary injunction related to Teva's Pantoprazole Tablets. In that decision, the Court found that Wyeth/Altana did not meet its burden of proving likelihood of success on the merits. Wyeth/Altana have appealed that decision.

Mylan updates on Lorazepam and Clorazepate antitrust cases

Mylan today announced that it intends to appeal a Jan. 24, 2008 decision by the U.S. District Court for the District of Columbia against Mylan and its co- defendants Cambrex Corporation and Gyma Laboratories in the last of the pending Lorazepam and Clorazepate antitrust cases. The first related suit had been filed in 1998. As previously disclosed, in June 2005, a jury in the district court had rendered a verdict against Mylan and its co-defendants. The parties subsequently filed various post-trial motions, and the January 24 decision resolved several of those motions. The district court ordered Mylan to pay $35,906,922. The court also ordered Cambrex and Gyma to pay $16,709,242 each, some or all of which may be subject to indemnification obligations by Mylan. Plaintiffs' motion for attorneys' fees remains pending. Mylan intends to immediately appeal the decision and will continue to vigorously defend itself in the litigation. Mylan Inc. is one of the world's leading quality generic and specialty pharmaceutical companies. The Company offers one of the industry's broadest and highest quality product portfolios, a robust product pipeline and a global commercial footprint through operations in more than 90 countries. Through its controlling interest in Matrix Laboratories Limited, Mylan has direct access to one of the largest active pharmaceutical ingredient (API) manufacturers in the world. Dey, L.P., Mylan's fully integrated specialty business, provides the Company with innovative and diversified opportunities in the respiratory and allergy therapeutic areas.

Endo Pharma filed a lawsuit against Impax on Oxymorphone HCl extended-release tablets

Endo Pharma and Penwest Pharma announced today that they have filed a lawsuit against Impax Lab in the United States District Court for the District of Delaware in connection with Impax's Abbreviated New Drug Application (ANDA) for Opana ER (Oxymorphone HCl) extended-release tablets . The lawsuit is in response to IMPAX's notice to Endo and Penwest, announced on December 17, 2007, advising of the FDA's acceptance for substantive review, as of November 23, 2007, of IMPAX's ANDA containing a Paragraph IV certification under 21 U.S.C. Section 355(j) forOxymorphone hydrochloride extended-release tablets CII. IMPAX stated in its Paragraph IV certification notice letter that the FDA requested IMPAX to provide notification to Endo and Penwest of this certification.IMPAX's Paragraph IV certification notice refers to certain Penwest patents listed in the FDA's Orange Book relating to the formulation of OPANA ER. The complaint filed today alleges infringement of certain of these Orange Book-listed patents.As previously disclosed, Endo and Penwest filed a lawsuit against IMPAX on November 15, 2007 in the United States District Court for the District of Delaware in response to a series of Paragraph IV certification notices that Endo and Penwest assert were wrongfully served on them by IMPAX. These prior Paragraph IV Certification Notices related to the same Orange Book-listed patents for OPANA ER and were served on Endo and Penwest after the acceptance of IMPAX's ANDA was rescinded by the FDA. Endo and Penwest continue to believe that these prior Paragraph IV Certification Notices are null, void and of no legal effect.OPANA ER has been granted new dosage form regulatory exclusivity that prevents the FDA from approving any ANDA for a generic version of OPANA ER for launch prior to June 22, 2009, the date such regulatory exclusivity expires.

Gilead’s loss, Cipla’s gain

The US Patent and Trademark Office’s (USPTO) rejection of Gilead Sciences’ patent application for the AIDS drug, Viread, is expected to have a strong impact in the Indian as well as global HIV/AIDS drug market. The rejection may affect the decision of the Indian Patent Office on Gilead’s patent application for Viread here. Last year, Cipla had filed a pre-grant opposition with the Indian patent office against Viread, the much sought after second line AIDS drug, arguing that the grant of the patent in India will make the HIV drug unaffordable to patients worldwide.
On Wednesday, USPTO rejected four patents on Viread, claiming the molecules are known. But the ruling is not final and Gilead claims that the patents will be upheld. “Now, since the patent application is rejected in the US, chances for the application getting rejected in India become high and Gilead will be forced to withdraw the application,” a patent attorney told FE.
According to analysts, Cipla will be benefited from the verdict. Cipla is marketing a generic version of tenofovir at a cost of $700 per person per year in India, while Gilead’s tenofovir costs $5,718 per patient per year in developing countries. However, Cipla officials refused to comment citing that the matter was sub judice.
Last year, Gilead signed license agreements with 11 Indian Companies for manufacturing and selling Viread in 95 countries, including India. Cipla, which refused Gilead’s licensing offer, challenged Viread’s validity by filing a pre grant opposition, apart from Delhi Network of Positive People, an NGO. However, Indian firms who entered into agreements with Gilead remain unfazed by the verdict. MM Srinivas Reddy, director, marketing, Hetero Drugs, told FE, “We are not worried at all over the verdict. Gilead has the chance to go for further appeal. Let the final verdict come.”
Gilead sells tenofovir alone and in combination with other drugs like Truvada and Atripla. Taken together, the three HIV treatments generated $3.1 billion in sales last year, according to the company reports. (Source: Financial express)

Why to change US patent system when its best in the world?

For years, Germany has been the world's leading exporter, buoyed by sales of high-end technology. People across the globe have benefited from Germany's life-saving drugs and state-of-the-art machinery, not to mention its unrivaled luxury automobiles.However, a recent effort by the United States to reform its patent system threatens to undermine German innovation and deprive Americans and the world of its benefits.The U.S. patent system has been an integral part of German technological development. American patents have helped spur German dominance in areas such as industrial machinery, chemicals, pharmaceuticals and advanced medical devices. They have also helped preserve the nearly one in four German jobs that are dependent on exports.
Between 2000 and 2005, more than 64,000 German inventions received patents from the U.S. Patent Office - roughly the same number of patents Germany issued to its own citizens.The appeal of the American patent system is not limited to Germans. Last year, the U.S. Patent Office granted more than 94,000 patents to foreign inventors. Activity in the U.S. Patent Office was 50 percent higher than the European patent offices combined.The American system is regarded as the strongest protector of patent rights in the world. Unfortunately, the U.S. Congress is considering "reforming" the system. A bill has already been passed by the House and is under consideration in the Senate. Proposed changes could have potentially devastating consequences to research-based industries, especially the pharmaceutical industry.
Europe's inventors have flocked to the U.S. Patent Office because the European patent system is far inferior to America's. Europe's extended post-grant review procedures and artificially low caps on damages for stolen patents undermine the value of European intellectual property. Other flaws include ineffective and slow prosecution of counterfeit and copyright infringement cases.America has reaped great benefits when foreign inventors use the U.S. patent system. Thanks to the development and innovation spurred by American patents issued to Germans, for example, the two countries have developed a remarkably close trade relationship, which has reinforced their close political ties.
Germany consistently ranks as America's top trade partner in Europe. Moreover, as of 2000, 50 percent of German foreign direct investment went to the United States. Similarly, America was the top investor in Germany. As a direct result of German-American trade, millions of jobs have been created on both sides of the Atlantic.Patent protections will play an even more important role in German-American trade as it becomes increasingly dominated by research-based industries such as pharmaceuticals, chemicals and high-tech machinery. The process of innovation is so costly in these sectors that they cannot survive without strong protection of intellectual property rights.
In the pharmaceutical industry, it takes on average about 10 years and $800 million to develop just one drug. Many attempts lead to dead ends. Of the few drugs that make it to market, more than 50 percent will never turn a profit.To continue the research necessary to develop new drugs, which have been credited with 40 percent of the increase in life expectancy over the past 20 years, drug companies must recoup all their losses on just a handful of drugs. When patent regimes allow generics to flood the market, this becomes impossible.
However, by passing the Patent Reform Act of 2007, Congress would replace many of the best aspects of the U.S. patent system with the worst aspects of the European system. It would hurt the United States, Germany and - in the long run - many consumers worldwide."Virtually all of the inventions which ultimately hastened economic development and lifted living standards - especially new technologies and manufacturing processes - were developed in societies with strong intellectual-property protections," according to a 2005 report, "The Economic Value of Intellectual Property." U.S. patent reform will only weaken international protection of intellectual property.
The patent-reform bill would reduce incentives to perform research and development, threaten jobs at home and abroad and damage trans-Atlantic trade relationships, which have brought wealth and vital goods to the United States and Europe.Congress should think twice before "fixing" a patent system that is the envy of the world.
(This is is an interesting article from GERNOT PEHNELT who is a lecturer of economics and research associate at the Friedrich-Schiller-University in Jena, Germany.)

supreme court stays proceedings before IP Board on Glivec case

The Indian Supreme Court (The Hindu) has stayed proceedings before the Intellectual Property Appellate Board (IPAB), regarding the hearing on the rejected patent application of Novartis’ cancer drug Glivec.
The development follows a Special Leave Petition (SLP) filed by Hyderabad-based Natco Pharma at the apex court, a lawyer familiar with the case told Business Line.
Natco’s SLP at the Supreme Court came after the Madras High Court said in November last year that a two-member bench comprising the Chairman and Vice-Chairman of the IPAB could look into the case. The Madras HC’s ruling seemed to go with the revised approach that the Government had earlier submitted to the court, where the Centre had made a similar suggestion.
The Centre had come up with a revised approach to get the IPAB to hear the rejection of Novartis’ Glivec patent application, after Novartis objected to the composition of the IPAB. The IPAB had former Patent Controller Mr S. Chandrasekaran, on it as a technical member. And Novartis had objected to this as he was head of the Patent Controller’s office when it had rejected Novartis’ application in January 2006.
All parties to the case, including Novartis, the Centre, generic companies like Ranbaxy and Cipla and the Cancer Patients Aid Association will now have to respond to the latest development at the SC within four weeks, the lawyer said.
The development at the Supreme Court on Monday comes even as the IPAB was scheduled to look into the rejection of Givec’s patent application on the same day.
The case on Novartis’ rejected Glivec patent application had shifted from the Madras HC to the IPAB after the latter was created last April, following a notification from the Centre. But the focus again shifted back to the Madras HC, with Novartis objecting to the appointment of the former Patent Controller as technical member on the IPAB. The Madras HC subsequently ruled on the issue late last year, following which Natco approached the apex court.

Merck, Schering-Plough to Cooperate in Vytorin Probe

Jan. 27 (Bloomberg) -- Merck & Co. and Schering-Plough Corp. will cooperate in the probe of Vytorin by New York Attorney General Andrew Cuomo, who wants to know if the pharmaceutical companies hid research on the cholesterol- lowering drug.
Cuomo's investigation focuses on the marketing of the drug and sales of the companies' shares before the negative results were made public, the attorney general's office said yesterday in an e-mailed statement.
A study released Jan. 14 showed that Vytorin, a combination of the drugs Zocor and Zetia which had $5 billion in sales in 2007, may be no more effective at reducing plaque buildup inside the arteries than Zocor alone. New York's Medicaid program for those with low incomes has paid about $21 million for Vytorin in the past two years rather than buying a cheaper generic version that might be at least comparable to the name brand, Cuomo said.
``We are aware of the subpoenas and will cooperate with the New York attorney general,'' said Schering-Plough spokeswoman Rosemarie Yancosek. ``We stand behind our products as we have done nothing wrong.''
``Merck received the subpoenas and will cooperate fully,'' said spokesman Chris Garland. ``Merck stands behind the safety and efficacy profiles of Zetia and Vytorin. We acted with integrity and good faith with respect to the trial.''
Stock Sales
The attorney general also sought information to determine whether insider sales of stock were appropriate and whether statements to investors were accurate. He declined, however, to pinpoint any specific trading in the shares of Merck, based in Whitehouse Station, New York, or Schering-Plough, based in Kenilworth, New Jersey.
Carrie Smith Cox, a Schering-Plough executive vice president, sold 900,000 shares for $28 million on April 20, according to a Securities and Exchange Commission filing. No reference to her was made in yesterday's statement. The company said on Jan. 22 that Cox followed procedures in making the sale.
``We will investigate and, when appropriate, hold accountable drug companies for engaging in irresponsible and deceptive conduct and any deceitful marketing of prescription drugs,'' Cuomo said in the statement.
The company-sponsored study from October 2002 to April 2006 measured the thickness of the carotid arteries of 720 patients with a predisposition to high cholesterol who took the largest dose of Vytorin over two years. A blocked carotid cuts blood supplies to the brain and can cause a stroke.
Lawmakers' Probe
Lawmakers are probing whether Schering and Merck acted improperly in their marketing for Vytorin, which cost an average of $3 a pill compared with 3 cents for Zocor.
Earlier this month, Representatives John Dingell and Bart Stupak, Michigan Democrats, sent letters asking the companies and the U.S. Food and Drug Administration for records related to their marketing of the products.
The FDA, meanwhile, has said it may take six months to accumulate the data from the Enhance trial before a decision can be made on whether to investigate the drug.
New prescriptions for Vytorin have fallen 22 percent and 23 percent for Zetia in the 10 days since the study was reported, according to James Kelly, an analyst with Goldman Sachs Group Inc.

Cypress Reaches Settlement with Glaxo Relating to Ranitidine Oral Syrup Products

Cypress Pharmaceutical, Inc. today announced that it has reached a settlement with Glaxo, part of the GlaxoSmithKline group of companies, resolving all disputes between the companies related to Cypress' generic ranitidine oral solution products and Glaxo's Zantac(R) syrup.
Under the terms of the settlement, Glaxo has agreed not to assert its patent against Cypress' new alcohol-free formulation of its generic ranitidine oral syrup. Cypress expects to launch the product immediately upon receiving FDA approval. As a result of the settlement, the parties filed a stipulation to dismiss their patent litigation pending in the U.S. District Court for the Southern District of New York.

Forest and Merz File Additional Lawsuit Against Generic companies for Patent Infringement of Memantine

Forest Lab, Merz Pharma announced that they have filed a second lawsuit in the U.S. District Court for the District of Delaware against additional companies for infringement of US5061703 (the '703 patent) which covers a method for the prevention or treatment of cerebral ischemia comprising the step of administering, to a patient in need thereof, an effective amount of an adamantane derivative like Memantine hydrochloride. The defendants named in the lawsuit include Dr. Reddy's Laboratories Limited, Genpharm Inc., Interpharm Inc., Mylan Pharmaceuticals Inc., Ranbaxy Laboratories Limited, Sun India Pharmaceutical Industries Limited, and related companies and subsidiaries thereof. The '703 patent expires in April 2010. Forest has applied for patent term extension which, if granted, would extend the '703 patent until September 2013.
As previously reported, Forest and Merz had received notification from several companies that they had filed Abbreviated New Drug Applications (ANDA) with Paragraph IV certifications to obtain approval to market generic versions of Namenda and commenced an action in patent infringement in the U.S. District Court in Delaware against such filers.

New rules for labeling changes for approved drugs

FDA issued (News from fdalawblog) a proposed rule that would “reaffirm [the Agency’s] longstanding position that” labeling changes for approved drugs, biologics, and medical devices may only be made to show newly acquired information or to “add or strengthen a contraindication, warning, precaution, or adverse reaction” when there is sufficient evidence to support the change.
FDA’s current regulations at 21 C.F.R. §§ 314.70(c), 601.12(f), and 814.39(d) allow changes to be made to drug, biologic, and device labeling in certain situations upon FDA’s receipt of a supplemental application, commonly referred to as a “changes being effect supplement,” or a “CBE supplement,” for drugs and biologics, and a Premarket Approval Application (“PMA”) supplement or Special PMA Supplement for devices. (For convenience, we use the term CBE supplement to refer to drug, biologic, and device labeling supplements.) FDA’s proposal, if finalized, would make explicit that CBEs may only be used to update newly acquired safety information, which FDA proposed to define as “data, analyses, or other information not previously submitted to the agency, or submitted within a reasonable time period prior to the CBE supplement, that provides novel information about the product.” For example, if a postmarket study suggests a more severe and significant adverse reaction than previously known, then a CBE supplement “may be appropriate;” but if a study only provides additional data on a known adverse reaction, a CBE supplement would not be appropriate. Further, according to FDA, a CBE supplement may only be used for labeling changes relating to “contraindications, warnings, precautions, or adverse reactions in circumstances when there is sufficient evidence of a causal association with the drug, biologic, or medical device.”
Because FDA’s proposal would merely codify existing FDA policy, it would not significantly alter Agency practice or establish new regulatory requirements. However, the proposed rule, if finalized, could give significant support to firms that invoke an FDA preemption defense in product liability cases where plaintiffs argue that firms should revise their own labeling in accordance with state law. Specifically, by revising its CBE supplement regulations to state that such applications require “newly acquired information,” FDA could limit the number of cases in which the results from certain studies could be used to support a stronger labeling warning and a product liability lawsuit. FDA states in the proposal that:
To the extent that state law would require a sponsor to add information to the labeling for an approved drug or biologic without advance FDA approval based on information or data as to risks that are similar in type or severity to those previously submitted to the FDA, or based on information or data that does not provide sufficient evidence of a causal association with the product, such a state requirement would conflict with federal law. In such a situation, it would be impossible to market a product in compliance with both federal and state law, and the state law would “stand[] as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress,” Hines, 312 U.S. at 67. Moreover, such a state law requirement relating to a medical device would constitute a requirement that is different from, or in addition to, a federal requirement applicable to the device, and which relates to the safety or effectiveness of the device. 21 U.S.C. 360k(a).
Indeed, this is precisely the issue the Supreme Court will consider later this year in Wyeth v. Levine - whether prescription drug labeling preempts state law product liability claims. Documents on the case are available from SCOTUSBlog. Last week, the Court agreed to hear the case.
In 2006, the Vermont Supreme Court ruled against Wyeth concerning the company’s labeling of PHENERGAN (promethazine HCl) and held that the FDC Act “provides a floor, not a ceiling, for state regulation.” FDA has previously stated (pages 3934-35) that “FDA approval of labeling under the [FDC Act] . . . preempts conflicting or contrary State law,” and that “FDA interprets the [FDC Act] to establish both a ‘floor’ and a ‘ceiling,’ such that additional disclosures of risk information can expose a manufacturer to liability under the act if the additional statement is unsubstantiated or otherwise false or misleading.”
FDA has invited comments on the Agency’s proposal regarding when safety information relating to a drug, biologic, or medical device should be considered “newly acquired.” All comments to the proposed rule are due March 17.

USFDA panel gave positive report for Alvimopan

A Food and Drug Administration panel gave a positive recommendation to a gastrointestinal treatment co-developed by GSK giving the drug the inside track to U.S. regulatory approval.
The FDA panel said the benefits of the drug Entereg (Alvimopan), co-developed by Glaxo and Adolor Corp of Pennsylvania, outweigh its risks. The drug treats a condition called post-operative ileus, in which the gastrointestinal system doesn't function properly after bowel surgery.
The condition, which annually afflicts hundreds of thousands of patients, is characterized by constipation and other gastrointestinal dysfunction.
The full FDA is scheduled to make a final decision on Entereg by Feb. 10. The agency is not bound to follow the recommendations of its panels, though it typically does.
The agency might extend its review period, however, because the panel on Wednesday said Adolor needs to come up with a better plan for ensuring that patients don't take the drug on a long-term basis. Safety data show that the drug can be dangerous to the cardiovascular system in the long term, the panel said.

Abbott got $1.2 billion fourth-quarter profit

Pharmaceutical and medical products maker Abbott Lab reported a $1.2 billion fourth-quarter profit Wednesday on the strength of strong drug sales worldwide, capping a year which saw international sales account for a majority of its business for the first time.
Blockbuster anti-inflammatory drug Humira led the way with a 43 percent jump in sales from a year earlier to top $3 billion in sales for 2007. Other Abbott drugs Depakote, TriCor and Kaletra also posted double-digit sales gains as pharmaceuticals helped it increase companywide sales by 16 percent.
Abbott's first-quarter outlook for earnings slightly below analysts' expectations sent its stock down despite the strong quarter. Shares fell $1.21, or 2 percent, to $56.28 in afternoon trading Wednesday.
Both the company and analysts painted an optimistic view of longer-term prospects for the North Chicago, Ill.-based company, however.
"Humira represents the primary growth and profitability driver for the company, and fourth-quarter performance continues to support our bullish view of the product," Cowen and Co. analyst Sara Michelmore said in a note to investors.
The fourth-quarter gain represented a turnaround from a loss a year earlier, when results were reduced by hefty acquisition charges for Kos Pharmaceuticals Inc. For the quarter ended Dec. 31, the company's net income amounted to 77 cents per share and compared with a loss of $476.2 million, or 31 cents per share, in the same period of 2006.
Revenue rose to $7.22 billion from $6.22 billion, exceeding the $6.97 billion estimated by analysts polled by Thomson Financial. Favorable exchange rates contributed 4.5 percent to the increase.
Adjusted earnings, excluding certain items, rose to 93 cents per share from 75 cents per share in the year-earlier period. That was a penny better than analysts' consensus estimate.
The 2006 fourth quarter included a $1.3 billion, or 85 cents-per-share, charge related to costs in the $3.7 billion acquisition of Kos Pharmaceuticals last year.
"Going forward, we're targeting higher growth markets, including emerging markets where we can distinguish Abbott from the competition with leading technology and innovative new products that meet the needs of patients and customers," CEO Miles White said on a conference call. "In 2007, we saw that focus pay off as our unique mix of businesses and new products delivered strong results."
Abbott's U.S. pharmaceutical sales increased 16.6 percent in the quarter and its international pharmaceutical sales rose 21.3 percent.
Humira, Abbott's top-selling product, recorded $527 million in sales in the most recent quarter. The company forecast 2008 Humira sales of about $4 billion.
Medical product sales climbed 11.5 percent, led by 15.2 percent growth in worldwide Diabetes Care sales and a 16.4 percent gain in international diagnostics sales. Nutritional product sales were up 11.2 percent over a year earlier, helped by strong results in emerging growth markets.
Abbott projected earnings per share of $3.20 to $3.25 for 2008 and 61 cents to 63 cents for the first quarter, both excluding items. Analysts had estimated earnings at 65 cents per share for the first quarter and $3.22 per share for the year.
Given the leadership positions of our major businesses, and the new products launching over the next year, we expect another year of strong results in 2008," Chairman and CEO Miles White said in a statement.

New warning for the use of Rosiglitazone

The European Medicines Agency (EMEA) has recommended updating the product information for rosiglitazone-containing antidiabetic medicines. Rosiglitazone is available in the European Union as Avandia (Rosiglitazone maleate), Avandamet (Rosiglitazone maleate/metformin) and Avaglim (Rosiglitazone maleate/Glimepiride).
During its January 2008 meeting, the Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a scientific opinion recommending the inclusion of a new warning stating that the use of Rosiglitazone in patients with ischemic heart disease and/or peripheral arterial disease is not recommended.
The CHMP also adopted an opinion recommending the addition of a new contraindication stating that rosiglitazone must not be used in patients with an acute coronary syndrome, such as angina or some types of myocardial infarction, because the medicine has not been studied in controlled trials in this specific patient group.
The recommended changes to the product information have been made as a follow-up measure to the re-assessment of the benefits and risks of rosiglitazone and pioglitazone, another antidiabetic medicine. This re-assessment was finalised by the CHMP in October 2007, concluding that the benefits of both medicines continued to outweigh their risks in their approved indications, but that the product information for rosiglitazone should be changed.
Looking more globally at antidiabetic medicines and the cardiovascular risk associated with their use, the CHMP and its Efficacy Working Party are currently re-examining their existing ‘Note for guidance on clinical investigation of medicinal products in the treatment of diabetes mellitus’ to decide whether changes are needed. A concept paper, setting out the main points for revision, is expected to be released in February.

USPTO rejected patent covering tenofovir disoproxil fumarate

The Public Patent Foundation ("PUBPAT") announced today that the USPTO has rejected four key HIV/AIDS drug patents held by Gilead Sciences that relate to the drug known generically as tenofovir disoproxil fumarate (TDF), a key weapon in the battle against HIV/AIDS. Gilead markets TDF in the USA under the brand name VIREAD and as a part of its ATRIPLA combination product.Roughly 40 million people worldwide are infected with HIV/AIDS, including more than 1.2 million Americans. The USFDA will not allow anyone other than Gilead distribute TDF in the United States because Gilead claims the four patents challenged by PUBPAT and now rejected by the Patent Office give them the exclusive right to do so."Every person suffering from HIV/AIDS has a right to get the best medical treatment science can offer, without any unjustified impediments placed in their way," said Dan Ravicher, PUBPAT's Executive Director. "This includes Americans infected with HIV/AIDS, who are entitled to the best pharmaceuticals possible without undeserved patents making them exorbitantly expensive."In its filings challenging the patents, PUBPAT submitted prior art that Gilead had not disclosed to the Patent Office during the patent application process that resulted in the patents being granted to the Foster City, California, biopharmaceutical giant. PUBPAT also described in detail how the prior art would have prohibited the patents from being issued in the first place, had the Patent Office had been aware of it. The Patent Office has now agreed with PUBPAT and found that each of the four Gilead Sciences patents are undeserved. Although Gilead has the right to respond to the Patent Office's rejections of the patents, third party requests for re-examination, like the ones filed by PUBPAT against the four Gilead TDF patents, are successful in causing the reviewed patents to either be revoked or changed more than two-thirds of the time."We are extremely pleased that the Patent Office has agreed with us that Gilead's TDF patents are invalid," said Ravicher. "This means that we are now well on the way towards ending the harm being caused to the public by Gilead's use of the patents to prevent anyone else from offering TDF to HIV/AIDS patients in the United States."The Gilead Sciences TDF patents challenged by PUBPAT that have now been rejected by the Patent Office are US5922695, US5935946, US5977089 and US6043230. Gilead has applied for similar patents on TDF in other countries throughout the world, including India, where they have received fierce opposition by non-profit AIDS patient groups.

USPTO grant contraceptive patent to Barr

Barr Pharmaceuticals, Inc. today announced the U.S. Patent and Trademark Office (PTO) issued US7320969 (which covers a method of contraception in a female in need thereof, the method comprising administering to the female a dosage comprising a combination of estrogen and progestin for a period of 81 to 89 consecutive days, followed by administration of a dosage consisting essentially of estrogen for a period of 2 to 8 consecutive days, wherein the estrogen that is administered in combination with progestin for the period of 81 to 89 consecutive days is administered in a daily amount equivalent to about 10 .mu.g to about 50 .mu.g of ethinyl estradiol, the estrogen that is administered for the period of 2 to 8 consecutive days is administered in a daily amount equivalent to about 5 .mu.g to about 10 .mu.g of ethinyl estradiol, and the progestin that is administered for the period of 81 to 89 consecutive days is administered in a daily amount of about 150 .mu.g of levonorgestrel) for the Company's SEASONIQUE(R) extended- cycle oral contraceptive. The patent will expire on January 30, 2024. The Company also announced that it has submitted the patent to the U.S. Food and Drug Administration (FDA) for issuance in the Orange Book.
"We are very pleased that the PTO has issued this important patent to protect our SEASONIQUE extended-cycle oral contraception intellectual property," said Bruce L. Downey, Barr's Chairman and CEO. "We remain committed to developing new products for our portfolio of extended-cycle oral contraceptives and to providing women with options as they consider their contraceptive alternatives."
The Company received FDA approval for SEASONIQUE (levonorgestrel/ethinyl estradiol tablets 0.15 mg/0.03 mg and ethinyl estradiol tablets 0.01 mg) extended-cycle oral contraceptive in May 2006. SEASONIQUE is indicated for the prevention of pregnancy and represents the next generation of extended-cycle oral contraceptives in a category the Company created with the launch of the SEASONALE extended-cycle oral contraceptive in 2003.

Drug filing/approvals

Teva got tentative approval for Lansoprazole: Teva Pharma announced today that the USFDA has granted tentative approval for the Company's Abbreviated New Drug Application (ANDA) to market its generic version of TAP Pharmaceutical's gastric-acid pump inhibitor, Prevacid(R) (Lansoprazole) Delayed-release Capsules, 15 mg and 30 mg. The brand product had annual sales of approximately $3.4 billion in the United States for the twelve months ended September 30, 2007, based on IMS sales data.Teva is currently in patent litigation concerning this product in the U.S. District Court for the District of Delaware involving Teva's paragraph IV certification to U.S. Patent Nos. 4,628,098 and 5,045,321. A trial was held in November, at the end of which the Court indicated it anticipates it will issue a decision before the June 7, 2008 expiration of the mandatory 30-month stay of FDA approval associated with the patent litigation.
Teva filed Para IV on Fenofibrate: Fournier Lab Ireland Ltd, a wholly-owned unit of Solvay Pharmaceuticals, was informed by Teva Pharmaceuticals that it has filed an ANDA - Abbreviated New Drug Application - with a Paragraph IV certification, seeking the approval of a generic version of TriCor® (Fenofibrate) 145mg NFE tablets in the United States.The Paragraph IV certification procedure challenges a number of US patents relating to TriCor® which run through the next decade.Such procedures are not unusual for branded products in the United States. Fournier Laboratories Ireland Ltd. remains fully committed to its fenofibrate franchise and is currently evaluating its options.
Banner Pharm got approval for Nimodipin: Banner Pharmacaps Inc., a leader in the pharmaceutical industry for the development of soft gelatin dosage form technology, today announced that the USFDA has granted approval for the Company's Abbreviated New Drug Application (ANDA) for Nimodipine 30 mg soft gelatin capsules. Banner's Nimodipine 30 mg capsules are the AB-rated generic equivalent of Bayer's Nimotop(R) 30 mg capsules, and are indicated for the treatment of subarachnoid hemorrhage, a form of cerebral bleed. Banner's product can be dispensed either in blister packaging or in bottles. Banner has partnered with Heritage Pharmaceuticals Inc., an Edison, New Jersey based generics company, for the exclusive US sales and marketing rights for Nimodipine.
USFDA approved Micafungin sodium sNDA: Astellas Pharma Inc. announced today that the USFDA has approved their Supplemental New Drug Application (sNDA) seeking approval for the use of MYCAMINE® (Micafungin sodium) for Injection in the treatment of patients with Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses. MYCAMINE was approved in 2005 for the treatment of patients with esophageal candidiasis and is the only echinocandin approved for the prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation.
NovaDel Pharma filed NDA for zolpidem tartrate Oral Spray: NovaDel Pharma Inc., a specialty pharmaceutical company developing oral spray formulations for a broad range of marketed treatments, announced today that the USFDA has accepted for filing its New Drug Application (NDA) for ZolpiMist(TM) (zolpidem tartrate) Oral Spray for the short-term treatment of insomnia. The company anticipates the FDA will complete its review by the end of the year consistent with PDUFA guidelines. NovaDel submitted its ZolpiMist(TM) application using the FDA's 505(b)(2) process based on data from two randomized, open-label, dose-ranging studies comparing ZolpiMist(TM) with Ambien(R) tablets in young and elderly healthy volunteers. Both studies compared the pharmacokinetics and safety of comparable doses of zolpidem administered as an oral spray versus tablets. The pharmacokinetic profiles were assessed by the maximum drug concentration (Cmax) and total exposure to drug (area-under-the-curve/AUC0-inf). The speed of drug absorption and level of sedation were also assessed in these studies. The results demonstrated bioequivalence between ZolpiMist(TM) and Ambien(R). Also included in the submission were data from process validation and registration stability batches produced at the intended commercial manufacturing facility.
USFDA has approved Colesevelam HCl: Daiichi Sankyo, Inc, said the USFDA has approved its cholesterol drug Welchol (Colesevelam HCl) to reduce both glucose levels and low density lipoprotein cholesterol levels (LDL-C) in adults with type 2 diabetes.

Teva got 180 days exclusivity for Granisetron HCl

USFDA’s requested for public comment to help resolve 180-day exclusivity issues concerning a generic version of the antinauseant and antiemetic drug KYTRIL (granisetron HCl) Injection. Specifically, in October 2007, FDA established a public docket in response to a letter from Teva Parenteral Medicines ("Teva"), in which the company argued that "the plain language and structure of the [FDC Act] compel the conclusion that Teva is entitled to 180-day exclusivity because Teva is the first applicant that submitted a substantially complete paragraph IV ANDA." Earlier today, FDA posted its January 17, 2008 response concluding that Teva did not forfeit 180-day exclusivity. This conclusion had been anticipated, because earlier this month Teva announced the approval of the company’s granisetron HCl ANDA with 180-day exclusivity.At issue in this case are the "failure to market" 180-day exclusivity forfeiture provisions at FDC Act § 505(j)(5)(D)(i)(I) added by the Medicare Modernization Act ("MMA") in 2003. Under these provisions, a generic applicant whose ANDA contains a paragraph IV patent certification and who is a "first applicant" eligible for 180-day exclusivity forfeits eligibility for such exclusivity if the firm fails to market the drug by the later of:(aa) the earlier of the date that is –(AA) 75 days after the date on which the approval of the application of the first applicant is made effective under subparagraph (B)(iii); or(BB) 30 months after the date of submission of the application of the first applicant; or(bb) . . . the date that is 75 days after the date as of which, as to each of the patents with respect to which the first applicant submitted and lawfully maintained a certification qualifying the first applicant for the 180-day exclusivity period under subparagraph (B)(iv), at least 1 of the following has occurred:(AA) In an infringement action brought against that applicant with respect to the patent or in a declaratory judgment action brought by that applicant with respect to the patent, a court enters a final decision from which no appeal (other than a petition to the Supreme Court for a writ of certiorari) has been or can be taken that the patent is invalid or not infringed.(BB) In an infringement action or a declaratory judgment action described in subitem (AA), a court signs a settlement order or consent decree that enters a final judgment that includes a finding that the patent is invalid or not infringed.(CC) The patent information submitted under [FDC Act § 505(b) or (c)] is withdrawn by the holder of the application approved under [FDC Act § 505(b)].In May 2004, Teva submitted the first ANDA to FDA containing a paragraph IV certification for a generic version of KYTRIL. The application also contained a paragraph III certification (date of patent expiration) and a "section viii statement" to a method-of-use patent. Roche, the NDA holder/patent owner, did not sue Teva (or any subsequent ANDA applicant) for patent infringement, and FDA tentatively approved Teva’s ANDA in August 2005. The patent subject to the paragraph III certification expired in December 2007; however, the 30-month period described in FDC Act § 505(j)(5)(D)(i)(I)(aa)(BB) above expired in November 2006.Teva argued that despite the expiration of the 30-month period, the firm remained eligible for 180-day exclusivity, which would be triggered by Teva’s commercial marketing of the drug.Specifically, Teva’s letter states:[T]he plain language and structure of the [FDC Act] compel the conclusion that Teva is entitled to 180-day exclusivity because Teva is the first applicant that submitted a substantially complete paragraph IV ANDA . . . . Teva’s exclusivity has not been forfeited . . . because there is a continuing possibility of ANDA-based patent litigation that could result in a "later" forfeiture event under [FDC Act § 505(j)(5)(D)(i)(I)]. . . .[The FDC Act] requires FDA to determine which is "the later of" (1) a determinate forfeiture trigger . . . "or" (2) a contingent forfeiture trigger . . . . But there is no conceivable way for FDA to determine which of those 2 potential triggers occurs "later" until (a) one of the contingencies that could give rise to a forfeiture trigger [under FDC Act § FDC Act § 505(j)(5)(D)(i)(I)(bb)] has occurred, or (b) none of the contingencies can occur. After all, it is impossible to know whether a contingent event has occurred before it does occur -- and twice as hard to determine that such an event will not occur until it no longer can occur.Teva echoed this argument in the company’s comments submitted to the docket FDA established to solicit public comment on acarbose (PRECOSE) 180-day exclusivity issues.FDA's granisetron docket response agrees with Teva’s argument. FDA states:We find that under the plain language of the statute, 180-day exclusivity is not forfeited for failure to market when an event under subpart (aa) has occurred, but - as in this case - none of the events in subpart (bb) has occurred. The "failure to market" provision results in forfeiture when there are two dates on the basis of which FDA may identify the "later" event as described in section 505(j)(5)(D)(i)(I). The provision does not effect a forfeiture when an event under subpart (aa) has occurred, but no event under subpart (bb) has yet occurred.This is not a situation in which it would be impossible for a later event to occur. Although at the time FDA made its exclusivity decision, there was no litigation regarding the ‘548 patent pending that could result in a forfeiture event under subitem (AA) or (BB) of subpart (bb), there was nevertheless the possibility that either an additional ANDA applicant would be sued as a result of a paragraph IV certification to the patent or one of the applicants would bring a declaratory judgment action against the NDA holder or patent owner. Either of these actions could result in a forfeiture event. In addition, the patent could be withdrawn by the NDA holder, resulting in a forfeiture event under subitem (CC). Because at least one of the events described in subpart (bb) could still have occurred and, if it did, would necessarily occur "later" than December 1, 2006, Teva did not forfeit its exclusivity.FDA also states in a footnote that:Inherent in the structure of the "failure to market" forfeiture provisions is the possibility that a first applicant would be able to enter into a settlement agreement with the NDA holder or patent owner in which a court does not enter a final judgment of invalidity or non-infringement (i.e., without a forfeiture event under subpart (bb) occurring), and that subsequent applicants would be unable to initiate a forfeiture with a declaratory judgment action. This inability to force a forfeiture of 180-day exclusivity could result in delays in the approval of otherwise approvable ANDAs owned by applicants that would market their generic drugs if they could but obtain approval. This potential scenario is not one for which the statute currently provides a remedy. (Source:FDAlawblog)

Pharma news in brief

Pantoprazole Sodium : Teva Pharma announced today that further to its press release dated December 24, 2007, the Company and Wyeth/Altana have agreed to extend their standstill agreement regarding generic Protonix(R) (Pantoprazole Sodium), through January 31, 2008. Under the agreement, Teva agreed not to ship additional product. This extension of the standstill period will allow the parties to continue their patent litigation settlement discussions

Barr in negotiation for patent dispute settlement: Barr Pharma today announced that the Company is in discussions with Ortho Women's Health & Urology, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. concerning a definitive agreement to settle the outstanding patent litigation involving Ortho Women's Health & Urology's oral contraceptive product, ORTHO TRI-CYCLEN(R) LO (norgestimate/ethinyl estradiol). The United States District Court for the District of New Jersey has postponed the trial date. The general terms and status of the anticipated settlement will not be disclosed by either party until a definitive agreement is reached.

Teva to aquire CoGenesys: Teva Pharma today announced that it has entered into a definitive agreement to acquire CoGenesys, Inc., a privately-held biopharmaceutical company with a broad based biotechnology platform and focused on the development of peptide- and protein-based medicines across broad therapeutic categories. CoGenesys was established in 2005 as a division within Human Genome Sciences Inc. (HGSI) to focus on early drug development and was spun off as an independent company in June 2006. Teva's existing biotechnology infrastructure includes product development and manufacturing in several countries. The Company also markets a portfolio of biopharmaceutical drugs outside the United States, including interferon alpha 2b, granulocyte colony-stimulating factor ("GCSF") and human growth hormone ("hGH"), while marketing hGH in the United States as well. Under terms of the agreement, Teva will pay a purchase price of $400 million cash, funded from its internal resources. The transaction has been approved by the boards of directors of each company and by the shareholders of CoGenesys and is subject to customary closing conditions (including approval under the Hart-Scott-Rodino Antitrust Improvements Act of 1976), and is expected to close during the first half of 2008.

Orphan drug status: Marshall Edwards announced today that its triphendiol (previously known as NV-196) has been granted orphan drug status by the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer and for the treatment of cholangiocarcinoma, or bile duct cancer. An orphan drug refers to a product that is intended for use in a disease or condition that affects fewer than 200,000 individuals in the United States. A grant of orphan drug status provides 7 years of market exclusivity for the orphan indication after approval by the FDA, as well as tax incentives, study design assistance, and eligibility for grant funding from the FDA during its development.

Merck V/S Arrow: Alendronate sodium trihydrate (Europe)

In a significant decision in Arrow v Merck the Court has held that a generic drug company could request a declaration that its product was obvious at the priority date of a patent application. If so, were the patent granted from that application to cover the product it would be invalid. The decision therefore opens up the possibility of generic companies (and any other would-be infringer) being able to clear a product’s path to market without having to wait for a patent to grant in order to bring invalidity or non-infringement proceedings.
In 2003, the English Court of Appeal revoked Merck’s EP998292 Patent (‘292), which covers method to treat osteoporosis patients with 70mg alendronate sodium trihydrate over a week, rather than 10mg once a day, on grounds of obviousness and lack of novelty, and because it was, in substance, a method of treatment of the human body by therapy. In 2004 the Opposition Division of the EPO revoked the same patent, and in 2006 the Technical Board of Appeal dismissed an appeal, finding the patent invalid for added matter. The Board did not consider arguments of obviousness and lack of novelty.
Alendronate preparations were first sold in 1995, with a 10mg oral formulation being introduced in 1997. In 1998, (priority date 22 July 1997) Merck applied for a 70mg once a week formulation, that patent (’292) being revoked by Arrow Teva and Generics (UK) in 2003, for lack of novelty, lack of inventive step, and because it was a method of treatment of the human body by therapy. That decision was upheld by the Court of Appeal in November 2003.
Following revocation of the ‘292 Patent, Arrow and other generic companies sold the 70mg product throughout Europe, the markets have become generic, and the cost of a 4 x 70mg pack has fallen from around £15-£18 to around £1-£2, no doubt resulting in a very substantial loss of revenue to Merck. During the course of prosecution of the ’292 Patent, Merck filed four divisional applications. These applications were stayed during the ’292 Patent opposition proceedings, but revived on the conclusion of those proceedings.The Examining Division of the EPO has found one of these divisional applications to be inventive, and allowed it to proceed to grant, as EP1175904 (“’904”). Claim 1 of ’904 is a “Swiss claim” directed to the use of alendronate to make a medicament for the treatment of osteoporosis in the human, where the medicament is orally administered as a unit dosage comprising about 70mg of alendronate, according to a continuous schedule having a once weekly dosing interval. The key idea therefore appears to be essentially the same as that of the ’292 Patent, namely to give osteoporosis patients 70mg of alendronate once a week.The Examining Division has justified this change in position, on the basis of the declaration by a Dr. Goldberg of Merck, which apparently gives details of the statistically significant effect arising from administration of 70mg of alendronate once a week, rather than a once a day 10mg tablet.
As the judge noted, Arrow v Merck was an exceptional case. Arrow had cleared the path for its generic version of Merck’s Fosamax by successfully applying to the court for revocation of Merck’s relevant European patent (UK) in 2003. The European Patent Office (EPO) also revoked the patent in opposition proceedings. Arrow then proceeded to build up substantial sales in the EU for its drug only for Merck to be granted a second European patent earlier this year, based on the same application as the revoked one, with several more patents that might follow and all of which Arrow potentially infringed as they contained similar claims to the revoked patent. Further Merck clearly intended to enforce its rights and refused to give undertakings not to sue Arrow and to withdraw the UK designations of the applications.
The court evidently sympathised with Arrow’s position. While it could not give the declarations that Arrow actually sought – as they involved the validity of non-UK designations of Merck’s patent and applications over which the High Court had no jurisdiction – the judge decided that the court could rule on whether Arrow’s alendronate (formulated as a sodium salt in a weekly dosage form) was obvious as at the priority date of the patent and applications. If obvious, then any patent that covered the product would be obvious too and so invalid.
This approach neatly avoided the limited circumstances in which declarations of invalidity of patents can by brought under the Patents Act 1977 and which Merck argued formed a complete bar to the relief sought by Arrow.
But more significant is the court’s view that businesses need commercial certainty in patent matters, as in any other, and that the court should assist in providing it where it properly could. In particular Merck’s applications could take a further year or more to be granted as patents during which time Arrow would be accumulating substantial potential liability if it infringed them. Merck could have avoided this effect on Arrow by giving the undertakings but it did not so there was a valid and valuable commercial purpose to the declaration for Arrow. This decision gives a potentially attractive additional tool to declarations of invalidity and non-infringement of patents for those wanting to establish whether or not they infringe a patent and, if there is a risk they do, to clear the path for bringing their product to market. Particularly useful is that, as the declaration on a product can be sought as soon as a patent application is published rather than having to wait for grant, a favourable declaration allows considerably earlier entry on to the market. The decision will therefore be of obvious interest to generics drugs companies though, as it is not being appealed, it needs to be seen whether judges in other cases will follow it, or decide it is restricted to its facts or to exceptional circumstances only, before its full potential can be assessed. (Source :Arrow v Merck [2007] EWHC 1900 (Pat), Anna McKay, Ralph Cox)

Ranbaxy and Dr Reddy settled patent disputes with innovators

Ranbaxy Laboratories Ltd and Dr Reddy’s Laboratories Ltd, India’s top two drug makers, will launch versions of a migraine drug grossing $985 million, or Rs3,891 crore, for GlaxoSmithKline towards the expiry of the patent on the medication, potentially earning profits of up to Rs540 crore more in 2009.
Ranbaxy on Monday said it had settled a lawsuit with the British patent holder GSK, and will enjoy a six-month market monopoly in the US, beginning December. Dr Reddy’s had said in October 2006 that it had been signed on by GSK as the authorized generics partner on Imitrex (sumatriptan succinate), the migraine drug whose patent expires in February 2009.
The Gurgaon drug maker could earn between $80 million and $90 million in the six month exclusivity period, while Dr Reddy’s could earn anything from $22-46 million. Analyst believe that Ranbaxy will earn more profit in comparison to DRL.

It was not immediately clear if Monday’s settlement by Ranbaxy was exclusive or it would share the period with a US unit of Cobalt Pharmaceuticals Inc., an Ottawa-headed firm with which GSK had settled a similar case in November 2006. A Ranbaxy spokesperson insisted the firm would enjoy a full exclusivity period for sumatriptan succinate (the chemical name of Imitrex) for 25mg, 50mg and 100mg strengths.
Monday’s development is similar to a market situation involving the two drug makers and Merck and Co. Ranbaxy, as the patent challenger on Merck cholesterol drug Zocor, had earned revenues of $60 million and Dr Reddy’s, as Merck’s partner for Zocor and prostrate cancer drug Proscar, had grossed $400 million in sales.
In an unrelated development, Dr Reddy’s on Monday said it had settled with Novartis AG not to introduce generic variants of Alzheimer’s drug Exelon that grossed the Swiss drug maker $199 million in 2006. Terms of the settlement were not disclosed.

ExelonÒ (rivastigmine tartrate) is a reversible cholinesterase inhibitor and is known chemically as (S)-N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl]-phenyl carbamate hydrogen-(2R,3R)-tartrate.Exelon Capsules contain rivastigmine tartrate, equivalent to 1.5, 3, 4.5 and 6 mg of rivastigmine base for oral administration. Inactive ingredients are hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, and silicon dioxide. Each hard-gelatin capsule contains gelatin, titanium dioxide and red and/or yellow iron oxides.

Vioxx settlement

More than 3,000 former users of Merck & Co's withdrawn Vioxx pain drug have already signed up to take part in a $4.85 billion settlement deal that a federal judge on Friday declared was in the best interests of both sides.
Attorneys for Merck and plaintiffs who claim to have been harmed by Vioxx were in U.S. District Court to give a status report on the settlement to Judge Eldon Fallon, who had presided over all federal Vioxx trials and is overseeing the settlement process.
A total of 57,167 potential participants have registered claims by this week's deadline and 3,065 have already opted to enroll in the settlement, which was announced in November.
Registrants will be divided into Vioxx users who had suffered heart attacks and those who suffered strokes after taking the pain medicine. Merck needs 85 percent of registered plaintiffs in each category to sign on to the settlement for the deal to move forward.
"We continue to expect to meet and exceed the enrollment thresholds, but we don't know when that will occur," said Ted Mayer, an outside counsel for Merck.
There are a series of enrollment deadlines over the coming months with a final opt-in date of October 30, a spokesman for Merck's legal team said.
Asked the most important thing to come out of Friday's hearing, Mayer said: "We have over 57,000 claims submitted for registration and that the enrollment process is underway."

FDA sued over Depakote

On January 14, 2008, Nu-Pharm Inc., a Canadian drug company formerly owned by Apotex, Inc., filed a complaint in the U.S. District Court for the District of Columbia against FDA seeking declaratory and injunctive relief with respect to the company’s Abbreviated New Drug Application ("ANDA") for divalproex sodium delayed-release 500 mg tablets. The drug is marketed by Abbott Laboratories under the trade name DEPAKOTE for the treatment of mania, migraine, and epilepsy, and was first approved in 1983 under NDA #18-723.According to the complaint, Nu-Pharm submitted ANDA #77-615 to FDA in March 2005 with paragraph IV certifications to two Orange Book-listed patents covering DEPAKOTE: U.S. Patent #4,988,731 ("the ‘731 patent") and #5,212,326 ("the ‘326 patent"). These patents are scheduled to expire on January 29, 2008; however, in December 2007, FDA granted Abbott pediatric exclusivity for the drug, thereby delaying generic approval under certain circumstances until July 29, 2008.Earlier, Abbott sued Nu-Pharm in the U.S. District Court for the Northern District of Illinois (Eastern Division) for infringement of both patents, thereby triggering a 30-month stay of approval of Nu-Pharm’s ANDA. According to Nu-Pharm, the 30-month stay expired on November 13, 2007, without any substantive merits ruling on patent infringement. Nu-Pharm then contacted FDA requesting that the Agency grant final ANDA approval.According to the complaint, in December 2007, FDA informed Nu-Pharm that the Agency would not grant final approval based on an order entered in a contempt proceeding in the U.S. District Court for the Northern District of Illinois (Eastern Division) in Abbott Labs v. Apotex. In that proceeding, the charged conduct was the submission of repetitive ANDAs by Apotex and Nu-Pharm to FDA for generic DEPAKOTE. In October 2007, the U.S. Court of Appeals for the Federal Circuit reversed the district court’s judgment of contempt "because the district court erred in finding Apotex in contempt when the conduct at issue was not within the express terms of the injunction." By way of background, in previous paragraph IV patent litigation in that case concerning Apotex’s ANDA #75-112 for generic DEPAKOTE, Judge Richard Posner, sitting by designation in the U.S. District Court for the Northern District of Illinois, ruled that Apotex’s product infringed the ‘731 and ‘326 patents, enjoined the company from manufacturing, using, selling, or offering to sell generic divalproex sodium, and stated that the effective date of approval of ANDA #75-112 would be no earlier than January 29, 2008 when the patents expire - without pediatric exclusivity. The decision was affirmed in 2005. Apotex subsequently entered into an agreement with Nu-Pharm under which Apotex would pay for the costs associated with preparing and submitting a new ANDA (i.e., ANDA #77-615) for generic DEPAKOTE and Nu-Pharm would take on the "litigation risks" arising from the submission of the ANDA.According to the Nu-Pharm complaint, FDA orally refused to grant final approval for ANDA #77-615 on January 9, 2008. Considering FDA’s decision to be final agency action, the company filed a complaint. Nu-Pharm alleges that FDA’s refusal to approve the company’s ANDA violates the FDC Act and the Administrative Procedure Act because "FDA’s decision violates the plain and unambiguous language of the [FDC Act], which provides that FDA shall immediately approve an ANDA where, as in this case, the applicable 30-month stay has expired" and there has been no finding of infringement or validity, and that FDA "has no lawful basis or authority to withhold final approval . . . based on a court order in a wholly separate contempt proceeding to which Nu-Pharm was not a party."(Source FDAlawblog)

Pharma news in brief

1. Aurobindo Pharma Ltd has received an approval from the USFDA to market its 300mg cefdinir capsules in the US market. This is company's 62nd ANDA approval. The drug falls under the anti-bacterial segment and is a generic equivalent of Abbott Laboratories' Omnicef. Earlier, the company also received the final approval for 125 mg/5 mL and 250 mg/5 mL oral suspension of this drug from the US FDA.
   
2. Daiichi Sankyo, Inc., announced today that the United States Food and Drug Administration (FDA) has approved Welchol(TM) (colesevelam HCl) to improve glycemic control (measured as hemoglobin A1C) in adults with type 2 diabetes mellitus in combination with metformin, sulfonylureas, or insulin, either alone or in combination with other anti-diabetic agents. Welchol is now the first and only medication approved to reduce both glucose levels and low density lipoprotein cholesterol levels (LDL-C). The ADA estimates that 20.8 million people in the United States have diabetes with more than 90 percent of these people having type 2 diabetes.(1) Forty percent of patients with type 2 diabetes also have high LDL-cholesterol.(2) Welchol is a new option that addresses both these chronic health conditions and provides physicians with a unique therapeutic approach for treating patients with type 2 diabetes
3. Cipla (News from blog site patent circle) has finally launched a generic onslaught on anti-cancer patented drug Tarceva and reported to be convinced that Tarceva is not patentable and has strong case to oppose despite patent granted in India. Following the generic launch, Roche has filed an infringement case against Cipla in the Delhi High Court, which came up for its first hearing on Friday. Cipla launched generic Tarceva at Rs. 1600 compared to Roche Rs. 4800 per tablet.Erlotinib hydrochloride, an active ingredient of Tarceva is granted Indian Patent No. 196774 (the ‘774 patent) by the Delhi Patent Office against the mail-box Application No. 537/DEL/1996 filed March 13, 1996. Under section 25(2) of the Patents Act 1970, the ‘774 patent statutorily can be opposed within one year from the date of grant of patent, which Cipla may likely consider opting for. Interestingly, Hyderabad-based generic company Natco filed a pre-grant opposition against the Tarceva mail-box Application but subsequently rejected by the Delhi Patent Office. According to Dr. Gopakumar Nair, “Erlotinib is a derivative of another known cancer drug gefitinib, a pre-1995 invention of European drug maker AstraZeneca. Since the Delhi Patent Office had denied a patent for this drug, a patent for its derivative will not be strong, and the generic company can get the patent revoked through a post-grant opposition.” Under section 25(2) the ‘774 patent can be opposed on any of the eleven grounds
   - wrongfully obtained the invention,- prior publication,- subject-matter claimed in already claimed in patent of earlier priority,- publicly known or publicly used in India before the priority date,- obvious and does not involve inventive step,- not patentable subject-matter under the Act,- lack sufficient and clear description of the invention, or method by which it is to be performed,- filed not within 12 months from the priority date,- failure to disclose information under section 8 of the Act,- fail to disclose or wrongly disclose the source and geographical origin of biological material used in the invention, and- anticipated having regard to the knowledge, oral or otherwise.
4. Ranbaxy succeded in invalidating enatiomer (On 10th January 2008) patent of Pfizer in Germany. The basic patent covering Atorvastatin still stands and there will be no change in marketing status of Lipitor in Germany.

Ranbaxy settle sumatriptan succinate patent dispute with GSK

Ranbaxy Laboratories Ltd has settled all matters relating to possible patent litigation with GlaxoSmithKline relating to sumatriptan succinate tablets, the generic version of GlaxoSmithKline's Imitrex tablets.The terms of the settlement, provide that Ranbaxy may distribute a generic version of sumatriptan succinate tablets (in the 25 mg, 50 mg and 100 mg strengths) in the US with an expected launch date in December, 2008. Additional terms of the settlement agreement were not disclosed.The annual market sales for sumatriptan succinate (Imitrex®) were USD 985 million.

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.

Innogenetics won infringement suit against Abbot on Hepatitis C Virus genotyping technology

Innogenetics announced that the United States Court of Appeals for the Federal Circuit yesterday evening has affirmed the U.S. District Court’s finding that Abbott Lab infringed Innogenetics’ patented Hepatitis C Virus (HCV) genotyping technology. The Federal Circuit also upheld the jury’s finding that Abbott pay Innogenetics damages for infringement and sanctions for making a baseless claim against Innogenetics, estimated to total approximately $US10 million.
In a decision i the Federal Circuit rejected a myriad of issues raised by Abbott in Abbott’s effort to overturn the unanimous jury verdict in Innogenetics’ favor. The Federal Circuit also affirmed the district court’s finding that Abbott should be sanctioned and pay Innogenetics’ attorneys fees related to Abbott’s baseless claim that Innogenetics had acted improperly in obtaining its US HCV genotyping patent. The result of the Federal Circuit decision is that Abbott must pay an estimated $US 10 million in damages to Innogenetics, using current exchange rates. During the appeal, Abbott challenged many of the rulings made by both the district court and the jury. In rejecting Abbott’s challenges, the Federal Circuit affirmed the district court’s finding that Abbott infringed claims 1, 2 and 3 of Innogenetics’ HCV genotyping patent; dismissed all challenges to the validity of claims 2 and 3 of the patent; affirmed the jury’s damages award; affirmed the district’s finding that the patent is enforceable; and affirmed the district court’s sanctioning of Abbott by ordering it to pay Innogenetics’ attorneys fees resulting from Abbott’s baseless assertion that the patent was not enforceable due to Innogenetics’ conduct before the United States Patent Office.
The Federal Circuit reversed the district court’s decision to summarily rule on the validity of one of the patent’s claims in light of one piece of prior art; finding instead that the district court should have allowed that question to be decided by a jury. The Federal Circuit thereby remanded this issue back to the district court. Importantly, because two of the three claims found to be infringed are unaffected by this ruling, this reversal will not affect either the determination that Abbott infringed Innogenetics’ HCV genotyping patent or the jury’s determination that Abbott must pay damages for its infringement. In reversing the district court’s permanent injunction against Abbott, the Federal Circuit replaced the permanent injunction against Abbott with a compulsory license requiring Abbott to pay Innogenetics a royalty on each future infringing product sold by Abbott in the United States, or made by Abbott in the United States and exported for sale worldwide. The Federal Circuit left it to the district court to precisely determine the amount of damages to be paid to Innogenetics, taking into account accrued interest and the increased value of the Euro. These proceedings also will result in the establishment of an appropriate future royalty payment that Abbott must pay to Innogenetics if it sells any more infringing HCV genotyping assays.
In September 2005, Innogenetics sued Abbott Laboratories alleging that Abbott was infringing the company’s US5846704 (“the ‘704 patent”), which covers a method of genotyping the Hepatitis C Virus. The court found the patent was infringed as a matter of law. On September 1, 2006, a jury returned a unanimous verdict for Innogenetics that the ‘704 patent was valid in all respects. On September 8, 2006, the same jury unanimously found that Abbott’s actions had been willful, and directed Abbott to pay Innogenetics $7 million in damages related to the infringement up to the time of the trial. On January 4, 2007, the judge in this case dismissed Abbott’s requests for a new trial, affirmed the jury’s finding that Abbott infringed the patent, that the patent was valid in all respects and approved the award of $7 million in damages. The judge overturned the jury’s unanimous finding that Abbott’s infringement had been willful. On January 10, 2007, the judge affirmed Innogenetics’ request for a permanent injunction against Abbott, enjoining Abbott from any further sales, use or export of products, including components, that infringe on Innogenetics’ patented genotyping technology. On January 15, 2007, Abbott filed an appeal of the district court case with the United States Court of Appeals for the Federal Circuit. Innogenetics filed a cross-appeal on January 24, 2007. On October 1, 2007, oral argument was held before a three-judge panel of the United States Court of Appeals for the Federal Circuit.

Teva got approval for generic Pravastatin 80 mg tablets

Teva Pharma announced today that the USFDA has granted final approval for the Company's Abbreviated New Drug Application (ANDA) for Pravastatin Sodium Tablets, 80 mg.
Teva's Pravastatin Sodium Tablets, 80 mg are the AB-rated generic equivalent of Bristol-Myers Squibb's Pravachol 80 mg tablets, and are indicated for treatment of certain hyperlipidemias and the primary prevention of coronary events. Teva is already marketing the 10 mg, 20 mg and 40 mg strengths of this product (teva was first Para IV filer and it fought back its exclusivity from FDA).

Lack of new drugs sparked EU raids

European Union antitrust regulators said yesterday that they are raiding pharmaceutical companies in a probe into why so few new medicines and drug makers are emerging.
EU antitrust chief Neelie Kroes said she is looking at the entire pharmaceutical industry and wants to know why generic drugs were so slow to be launched in Europe. Generic medicines are made by other companies after the original developer of the drug loses its exclusive patent rights.
The European Commission said it is conducting inspections at the European premises of a number of pharmaceutical makers - both research-based and generic - including some based outside Europe.
U.S.-based Pfizer, Britain's GlaxoSmithKline and Sanofi-Aventis of France - the world's three biggest drug makers - along with Anglo-Swedish AstraZeneca, Merck Sharp & Dohme, Johnson & Johnson's Belgian unit, U.S.-based Wyeth, and Sandoz International GmbH, the generics division of Swiss company Novartis, confirmed that they had been the target of surprise raids and were co-operating with regulators.
Ms. Kroes said the EU is working closely with U.S. officials - "we're not the only one active in this," she said.
The EU executive will examine whether companies were deliberately preventing new firms from entering the market by abusing patent rights and launching "vexatious litigation" to ward off potential rivals.
It said the probe was partly triggered by its 2005 case against AstraZeneca in which the company was fined €60-million ($90-million) for filing misleading information to patent offices to delay generic versions of its ulcer drug Losec for most of the 1990s.
Fewer new medicines are reaching the market, regulators said, one sign that competition may not be working.
Europe spends €200-billion on medicines every year, or €400 per person.
Most of that cost is carried by state health insurance programs.
Pharmaceutical companies have argued that EU action to restrict patents would cost them billions of euros worth of research and development invested in new drugs, which get little or no return if cheaper generic drugs are allowed on the market.

Impax filed lawsuit against Medicis for generic minocycline hydrochloride extended-release tablets

IMPAX Lab announced that it has filed a lawsuit against Medicis Pharmaceutical Corporation in the United States District Court for the Northern District of California requesting a declaration that IMPAX does not infringe any valid claims of US5908838 (which covers A method for the treatment of acne using tetracycline antibiotic) related to IMPAX's filing in October 2007 of an Abbreviated New Drug Application (ANDA) for minocycline hydrochloride extended-release tablets, a generic version of Solodyn(R).IMPAX's ANDA does not contain any patent certification under Paragraph IV of the Hatch-Waxman amendments because no patents for the SOLODYN(R) product are listed in Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book), published by the U. S. Food and Drug Administration. Certain antibiotic products are not subject to these Hatch-Waxman procedures and, therefore, do not have patents listed in the Orange Book and are not subject to the patent certification requirements.Medicis Pharmaceutical Corporation markets SOLODYN(R) tablets for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older. U.S. sales of SOLODYN(R) tablets were approximately $216.7 million in the 12 months ended November 30, 2007.

Pharma news in brief

• UCB announced today that the New Drug Application (NDA) for the use of Keppra XR(TM) (levetiracetam) extended- release tablets in the adjunctive treatment of partial onset seizures in adults with epilepsy has been accepted for filing by the U.S. Food and Drug Administration (FDA).

• The European Medicines Agency (EMEA) has been formally notified by Marvel LifeSciences Ltd of its decision to withdraw its applications for a centralised marketing authorisation for the medicines Insulin Human Rapid Marvel, Insulin Human Long Marvel and Insulin Human 30/70 Mix Marvel.

• The Reyataz (atazanavir) package insert was revised to include information regarding the administration of atazanavir and/or atazanavir/ritonavir with food, proton pump inhibitors, H2 receptor antagonists, acetaminophen, and fluconazole. Additionally, dosing information in patients with renal impairment was included

• USFDA has issued a public health advisory to alert patients and healthcare professionals about important safety information concerning the drug Edetate Disodium. There have been cases where children and adults have died when they were mistakenly given Edetate Disodium instead of Edetate Calcium Disodium (Calcium Disodium Versenate) or when Edetate Disodium was used for "chelation therapies" and other uses that are not approved by the FDA. As a result, FDA is reviewing the benefit/risk profile of Edetate Disodium to determine if the benefits for its intended use continue to outweigh the serious risks.

• Dr Reddy's Laboratories Ltd has launched Supanac (Diclofenac potassium immediate release 50 mg tablets) in India, increasing its offering in the Rs 2700 crore ( $688 million) NSAID market.

• Pfizer Inc and Scil Technology GmbH (Scil) have signed a licensing agreement with Scil Technology GmbH (Scil) to develop and commercialise CD-RAP, Scil's cartilage specific growth factor. Under this agreement, Pfizer will obtain a worldwide exclusive license to develop and commercialise CD-RAP. In addition to receiving royalties on the sale of any products that may be commercialised under this agreement, Scil is eligible for upfront and milestone payments of approximately US $250 million depending on the achievement of various development and regulatory milestones.

• Nycomed announced today that the Food and Drug Administration (FDA) approved Alvesco(ciclesonide) Inhalation Aerosol in the United States for the maintenance treatment of asthma and as prophylactic therapy in adult and adolescent patients aged 12 years and older. ALVESCO(R) is an inhaled corticosteroid with novel release and distribution properties. Commercialisation and marketing of ALVESCO(R) will be achieved through a U.S. commercial partner.

• Teva Specialty Pharmaceuticals, the U.S. respiratory therapy unit of Teva Pharmaceutical Industries Ltd. (Nasdaq: TEVA) and UCB (Euronext: UCB) today announced an agreement to co-commercialize Teva's U.S. respiratory medicines. The initial product to be jointly promoted in the U.S. is Teva's ProAir(R)HFA (albuterol sulfate) Inhalation Aerosol. ProAir(R)HFA is the number-one branded hydrofluroalkane (HFA) albuterol sulfate inhaler in the U.S. Additionally, the agreement will provide UCB future joint promotion opportunities with other products in development by Teva Specialty Pharmaceuticals. Financial terms of the agreement were not disclosed.

• Dynogen Pharmaceuticals, Inc. today announced that the Company has acquired from Arachnova Therapeutics, Ltd. all of its worldwide patent rights and know-how related to DDP225 in an asset purchase agreement. The Arachnova patent rights, which include granted patents and pending applications related to the use of DDP225 for the treatment of functional bowel disorders, genitourinary (GU) disorders and pain, complement and enhance Dynogen's existing extensive worldwide patent estate related to DDP225. Financial terms of the agreement were not disclosed.

Hi-tech Pharma got final approval of fluticasone propionate nasal spray

Hi-Tech Pharma announced today that the USFDA has granted final approval to the Company's Abbreviated New Drug Application (ANDA) for fluticasone propionate nasal spray, 50mcg. Hi-Tech's fluticasone propionate nasal spray is the AB-rated generic equivalent of GlaxoSmithKline's Flonase(R), which is used in the management of the nasal symptoms of seasonal and perennial allergic and non-allergic rhinitis. Sales of branded and generic fluticasone propionate nasal spray, 50mcg was over $700 million for the 12 months ended June 2007 according to IMS sales data. Hi-Tech will begin immediate shipment of fluticasone propionate nasal spray, 50mcg.