Memantine hydrochloride (Namenda) 5 mg and 10 mg Tablets: Lupin entered into licensing agreement with innovator

Indian Pharma Giant M/S Lupin Pharma has announced that it has settled the litigation with innovator Forest Lab and Merz Pharma, which was pending in Delaware District Court, Maryland District Court and District of Columbia w.r.t generic version of Memantine hydrochloride (Namenda) 5 mg and 10 mg tablets.

Innovator has listed following patent in Orange Book for Memantine hydrochloride 5 mg and 10 mg tablets and sued Lupin and other generic players for the infringement of the same:

US5061703 (Expiry: April 11, 2015): The patent 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 Memantine (The said patent has got five years of patent term extension as reported by us Here )


Under the terms of agreement, Lupin will have a license under the required patents to launch its generic Memantine hydrochloride (Namenda) 5 mg and 10 mg tablets in January 2015 or earlier in certain unspecified circumstances. Importantly, Lupin would be able to market generic version almost 3 months earlier from the patent expiry date.

Earlier, the various generic players like Barr Lab, Cobalt Lab, Lupin, Orchid, Teva Pharma, Upsher-Smith Lab, Genpharm, Sun, Ranbaxy and Wockhardt filed ANDA with Paragraph patent IV certification against ‘703 patent. Subsequently, innovator sued various generic players for the infringement of ‘703 patent in U.S. District Court for the District of Delaware. Also, innovator sued Lupin in Delaware District Court, Maryland District Court and U.S District Court for the District of Columbia.

Earlier in September, 2009, the chief judge honorable G.M. Sleet of U.S. District Court for the District of Delaware has signed off on a request to dismiss M/S Upsher-Smith Lab (and 3 other generic players like Wockhardt, Amneal Pharmaceuticals, Apotex) from a patent infringement lawsuit that innovator Forest Labs and Merz Pharma brought to thwart the generic challenge to the Alzheimer's drug Memantine (Namenda) hydrochloride 5 mg and 10 mg tablets. Also in Oct, 2009, generic player Sun Pharma has agreed to launch generic version after the expiry of ‘703 patent.

Further, generic players like Orchid, Mylan and Cobalt are still in litigation with innovator for this product.

The generic players were not able to invalidate the method of use patent of this billion dollar molecule, till date. Further, 3 months earlier market entry (from patent expiry) is a favorable situation for Lupin to consolidate it’s generic version before further generic erosion after the patent expiry.

Montelukast sodium (Singulair): USPTO upheld the validity of compound patent during re-examination

Refer to our earlier post on Montelukast reexamination Here, Now, an article published in reuters (here ) reported that USPTO has upheld the validity of the key patent during re-examination. Now, generic version would be blocked till compound patent expiry in Aug 3, 2012.

Background

Earlier, the United States Patent & Trademark Office (USPTO) had accepted the request of a Independent firm Article One Partners LLC on Ex partes re-examination of blockbuster anti-allergic medication Montelukast’s (Singulair) key patent.

Innovator Merck has listed following disputed patent in Orange Book for Montelukast’s (Singulair) 10 mg tablets and 4 mg granules:

US5565473 (Expiry: Aug 3, 2012): which covers unsaturated hydroxyalkylquinoline acids as leukotriene antagonists, including Montelukast as product.The said patent is a blocking patent for other generic players and is a barrier to generic entry.

In March 2009, a firm that specializes in challenging the validity of patents has requested the USPTO to re-examine innovator Merck’s Orange Book listed patent US5565473 for Montelukast Tablets (Singulair). Independent firm Article One Partners LLC announced that its online community found two pieces of evidence that suggest the asthma and allergy drug's key ingredient isn't novel. Law firm has alleged that innovator during prosecution of ‘473 patent has not disclosed some articles authored by Merck's scientist Dr. Robert Young (who proposed a receptor model on anti-allergic effects). Further, law firm had alleged that the said article were very important for patentability determination of ‘473 patent.

Earlier, U.S. District Court for the District of New Jersey has upheld the validity of said patent and opined that generic version of M/S Teva pharma would infringe the compound patent (as reported by this blog Here )

Omeprazole Delayed Release 20 mg and 40 mg Capsules (Prilosec OTC): CAFC upheld Dr. Reddy’s non-infringement strategy

The Court of Appeal for Federal Circuit(CAFC) has affirmed (Here) a summary judgment decision by U.S District Court for the District of New York on Omeprazole Delayed Release 20 mg and 40 mg Capsules (Prilosec OTC), wherein, court has opined that generic player Dr. Reddy’s generic version of Prilosec OTC would not infringe innovator Astra Zeneca’s following Orange Book listed patents:

US5900424 (Assignee: Astra Aktiebolag; Date of grant: May 4, 1999; Expiry: May 4, 2016):

The said patent has following independent claims :

Claim 1. An omeprazole magnesium salt having a degree of crystallinity which is higher than 70% as determined by x-ray powder diffraction.

Claim 20. In a process for the manufacture of a crystalline magnesium salt comprising, (a) treating omeprazole or a salt thereof with magnesium alcoholate in a solution, (b) crystallizing magnesium omeprazole and (c) isolating the obtained crystalline magnesium omeprazole, wherein the improved process comprises separating inorganic salts from the reaction mixture prior to the crystallization step by the addition of water.

US5690960(Assignee: Astra Aktiebolag; Date of grant: November 25, 1997; Expiry: Nov 25, 2014): The said patent has following independent claims:

Claim 1. A stable oral formulation comprising: a core containing a magnesium salt of omeprazole said salt having more than 70% crystallinity as determined by x-ray powder diffraction; a subcoating layer; and an enteric coating layer, whereby the thickness of the enteric coating layer does not effect the release of omeprazole into solution at the pH predominantly present in the small intestine.

Claim 10. A process for the manufacture of a formulation of a pharmaceutical composition for the oral administration of magnesium omeprazole comprising the steps of: (a) forming a core material containing magnesium omeprazole salt said salt having at least 70% crystallinity as determined by x-ray powder diffraction; (b) applying in the presence of water at least one subcoating layer onto the core; (c) further applying in the pittance of water at least one enteric coating layer onto the subcoated core; and drying the prepared formulation.

Claim 22. An improved oral pharmaceutical composition containing a core of omeprazole salt with a subcoating and an enteric coating wherein the improvement comprises magnesium omeprazole salt having more than 70% crystallinity as determined by x-ray powder diffraction.

Discussion: After ANDA filing by Dr. Reddy with Paragraph IV certification with non-infringement grounds on above patents, innovator Astra sued generic player in U.S District Court for the District of New York for the infringement of above patents in July 27, 2007.

Further, innovator alleged that Dr. Reddy’s generic version will be covered under the scope of above patents. However, Dr. Reddy prepared the generic version which was amorphous with 1% crystalline content. Also, Dr. Reddy’s were not using water during crystallization process as covered in ‘424 patent.

However, innovator alleged that the generic version contains 5-8% of water, which would infringe the claim 20 of ‘424 patent. Further, during Markman hearing on disputed claim term by “the addition of water” the court opined that Dr. Reddy’s process has not used water during manufacturing the amorphous product and the said water can be attributed to atmospheric water adsorbed/absorbed on Dr. Reddy’s amorphous product or was prsent in the starting material used for the manufacturing of amorphous product.

In the light of above, U.S District Court for the District of New York issued Summary Judgment opinion in March, 2010 in favor of Dr. Reddy’s.

Paragraph IV Patent Certifications Reported by USFDA as of December 7, 2009

1. Adapalene 0.30% Topical Gel (Differin): Paragraph IV filed on Sep 15, 2009

2. Colesevelam Hydrochloride 625 mg (Welchol ) Tablets: Paragraph IV filed on July 1, 2009

3. Fulvestrant 50 mg/mL, 2.5 mL and 5 mL syringe (Faslodex): Paragraph IV filed on Oct 1, 2009

4. Levofloxacin 25 mg/mL Oral Solution (Levaquin): Paragraph IV filed on July 30, 2009

5. Linezolid 2 mg/mL, 300 mL bag Injection (Zyvox): Paragraph IV filed on Sep 1, 2009

6. Ropinirole Hydrochloride 6 mg Extended-release Tablets: Paragraph IV filed on July 22, 2009

Source: USFDA para IV certification list Here

Atorvastatin (Lipitor): Pfizer sued Dr Reddy’s for the infringement of Polymorph patent

Innovator Pfizer has sued generic player Dr. Reddy’s on Dec 8, 2009 for filing ANDA with Para IV certification against Orange Book listed patents for Atorvastatin (Lipitor) tablets in the U.S. District Court for the District of Delaware

Innovator has asserted following polymorph patent against generic player:

US5969156 (Expiry: June 8th, 2017): Which covers various hydrated Polymorphs of Atorvastatin (Form I, II and IV)

As per complaint filed in the U.S. District Court for the District of Delaware, innovator has requested court to block generic version till the expiry of crystalline polymorphic form patent.

Earlier, Dr. Reddy’s lab send Para IV certification letter to innovator Pfizer against Orange Book listed patents for Atorvastatin (Lipitor) tablets on Oct 26, 2009 .

Venlafaxine HCl (Effexor XR) Capsules: Mylan Announced Settlement With Innovator

Generic player Mylan announced (in a press release Here) that its subsidiary Mylan Pharmaceuticals Inc. has entered into settlement and license agreements with Wyeth, now part of Pfizer, relating to Venlafaxine HCl (Effexor XR) 37.5, 75 and 150 mg Capsules.

Following patents are listed in Orange Book w.r.t Venlafaxine HCl (Effexor XR) 37.5, 75 and 150 mg Capsules:

US6274171 (Expiry: September 20, 2017) Link

US6403120 (Expiry: September 20, 2017) link

US6419958 (Expiry: September 20, 2017) Link

US4535186 (Expiry: June 13, 2008) Link

US5916923 (Expiry: December 28, 2013) Link

US6444708 (Expiry: December 28, 2013) Link

Earlier, innovator Wyeth had sued Mylan for the infringement of ‘171, ‘120 and ‘958 patents in the West Virginia North District Court in 2007.

Pursuant to the license agreement, Mylan will be granted a non-exclusive license to the relevant patents that would permit Mylan to launch Venlafaxine HCl XR Capsules in the U.S. on or after June 1, 2011, or earlier in limited circumstances. Additional details of the agreement remain confidential.


Earlier, innovator had settled with generic players like Impax, Osmotica, Wockhardt, Sun pharma, Lupin, Anchen and Teva on this product.

Venlafaxine HCl ER Capsules had U.S. sales of approximately $2.9 billion for the same strengths for the 12 months ending Sept. 30, according to IMS Health.

Venlafaxine extended release is chemically the same as normal venlafaxine. The extended release version (sometimes referred to as controlled release) controls the release of the drug into the gastrointestinal tract over a longer period than normal venlafaxine. This results in a lower peak plasma concentration. Studies have shown that the extended release formula has a lower incidence of patients suffering from nausea as a side effect resulting in a lower number of patients stopping their treatment due to nausea.

(Source: the report is based on Mylan press release and some earlier posts of IP Pharma Doc on this product)

Ramelteon (Rozerem) 8 mg Tablets: Watson filed ANDA with Para IV certification

Watson Pharmaceuticals confirmed (in a press release Here ) that its subsidiary, Watson Laboratories filed an Abbreviated New Drug Application (ANDA) with the U.S. Food and Drug Administration seeking approval to market Ramelteon (Rozerem) 8 mg Tablets.

Innovator has listed following patent in the Orange Book for this product:

US6034239 (Expiry: Mar 6, 2017): The patent covers Ramelteon as product

Subsequently, in an attempt to block generic version of Ramelteon (Rozerem) 8 mg Tablets, innovator Takeda has filed an infringement action (based on '239 Patent) against generic player Watson in U.S. District Court for the District of Delaware. Earlier, innovator has sued generic player Teva for filing ANDA with Para IV certification.

As per press release, Watson believes it may be a "first applicant" to file an ANDA for Ramelteon (Rozerem) 8 mg Tablets, accordingly, may be entitled to 180 days of shared generic market exclusivity.

Earlier, innovator got approval to market Ramelteon (Rozerem) 8 mg Tablets on Jul 22, 2005. For the twelve months ending September 30, 2009 Ramelteon (Rozerem) 8 mg Tablets had total U.S. sales of approximately $91 million according to IMS Health data.

Atorvastatin (Lipitor): Pfizer sued Kremer-Urbans LLC and KUDCO for the infringement of Polymorph patent

Innovator Pfizer has sued generic player Kremer-Urbans LLC and its partner KUDCO for filing ANDA with Para IV certification against Orange Book listed patent for Atorvastatin (Lipitor) tablets in the U.S. District Court for the District of Delaware

Innovator has asserted following polymorph patent against generic player:

US5969156 (Expiry: June 8th, 2017): Which covers various hydrated Polymorphs of Atorvastatin (Form I, II and IV)

As per complaint filed in the U.S. District Court for the District of Delaware, innovator has requested court to block generic version till the expiry of crystalline polymorphic form patent.

The other Para IV filers on this product are Teva, Cobalt, Apotex, Matrix (Mylan), Dr. Reddy and Kremer-Urbans LLC and KUDCO

Earlier, Ranbaxy (First para IV filer) had settled its pending patent litigation on Lipitor and Caudet on June 18, 2008 and will launch its generic product in November, 2011

Valacyclovir Hydrochloride (Valtrex) 500 mg and 1 g tablets: Ranbaxy Launched Generic Version

Generic pharma giant Ranbaxy has launched generic version of Valacyclovir hydrochloride (Valtrex) 500 mg and 1 g tablets in USA on November 25, 2009.

Earlier, Ranbaxy was the first company who challenged innovator Glaxosmithkline (GSK) following Orange Book listed patent:

US4957924 (Expiry: Dec 23, 2009): Which covers Valacyclovir as product.

Subsequently, innovator sued Ranbaxy in New Jersey District Court in 2003. Afterwards, Ranbaxy got final approval from USFDA for this product on January 31, 2007 .

Further, as per paragraph IV patent litigation settlement agreement in July, 2007 with innovator Glaxosmithkline (GSK), Ranbaxy agreed to enter into the market in later half of 2009. Also, Ranbaxy entered into licensing agreement with innovator on two Orange Book listed patents US5879706 and US6107302 (both patents would expire on Jul 19, 2016), which covers polymorph and formulation of Valacyclovir.

Importantly, Ranbaxy is first Para IV filer for this product; accordingly, Ranbaxy would enjoy financially rewarding 180 days “First To File” market exclusivity.

Ranbaxy has manufactured the Valacyclovir hydrochloride 500 mg and 1 g tablets from it’s New Jersey based subsidiary Ohm Laboratories.

The other generic players who have received tentative approval from USFDA for this product are Dr. Reddy (June 26, 2009), Sandoz (July 30, 2007), Teva (October 4, 2007), Mylan (January 30, 2007), Watson (January 18, 2007). The other generic players would be able to launch their generic version after the expiry of 180 days exclusivity of Ranbaxy.

Valacyclovir tablets (Valtrex) 500 mg and 1 g were approved by USFDA on Jun 23, 1995 and are indicated for the treatment of herpes zoster, treatment of genital herpes, treatment of cold sores, and suppression of genital herpes in immunocopetent and HIV-infected individuals, reduction of risk of heterosexual transmission of genital herpes.

As per investment research firm IMS, the annual USA sales for Valacyclovir tablets 500 mg and 1 g is about 2.2 billion dollars.

Related news:
http://www.advfn.com/news_UPDATE-Ranbaxy-Launches-Generic-Valtrex-In-US-Shares-Rise_40540383.html

http://topnews.net.nz/content/21068-ranbaxy-introduces-glaxos-valacyclovir-american-market

Fluocinonide (Vanos cream) and Ciclopirox Olamine (Loprox gel): Glenmark settled patent litigation with innovator

Generic player Glenmark announced (in a press release Here ) the Paragraph IV patent litigation settlement with innovator Medicis Pharmaceutical on Fluocinonide (Vanos) cream and Ciclopirox Olamine (Loprox) gel topical formulations.

Fluocinonide (Vanos) 0.10% cream
Earlier, innovator Medicis sued Glenmark in New Jersey District Court in June, 2009 for the infringement of following Orange Book listed patents on Fluocinonide (Vanos ) 0.10% cream:

US6765001 (Assignee: Medicis Pharmaceutical; Date of Grant: July 20, 2004; Expiry Dec 21, 2021): Which covers a composition comprising One or more corticosteroids, wherein one corticosteroid comprises fluocinonide; Two or more penetration enhancers selected from the group consisting of diisopropyl adipate, dimethyl isosorbide, propylene glycol, 1,2,6-hexapetriol, and benzyl alcohol; and one or more of the group consisting of solvents and emulsifiers, wherein the penetration enhancers are present in a ratio to a total of the penetration enhancers, and solvents and emulsifiers of at least about 0.90.

US7220424 (Assignee: Medicis Pharmaceutical; Date of Grant: May 22, 2007; Expiry: Jan 7, 2023): which covers a method of delivering corticosteroids to skin comprising: Topically applying a composition comprising one or more corticosteroids with two or more penetration enhancers, and one or more of the group consisting of solvents and emulsifiers, wherein the penetration enhancers are present in ratio to a total of the penetration enhancers, and solvents and emulsifiers of at least about 0.90, and wherein the penetration enhancers comprise two or more of the group consisting of propylene glycol, diisopropyl adipate, dimethyl isosorbide, 1,2,6 hexanetriol, and benzyl alcohol

Under the terms of the Settlement Agreement, Glenmark will be able to market and distribute its generic version of Fluocinonide (Vanos cream) under license from Medicis as early as December 2013, or earlier in certain circumstances

Ciclopirox Olamine (Loprox) 0.77% Gel
Earlier, innovator Medicis sued Glenmark in New Jersey District Court for the infringement of following Orange Book listed patents on Ciclopirox Olamine (Loprox) 0.77% Gel:

US7018656 (Assignee: Aventis Pharma Deutschland ; Date of Grant: March 28, 2006; Expiry: Sep 5, 2018): which covers a gel composition comprising: at least one compound chosen from 1-hydroxy-4-methyl-6-cyclohexyl-2(1H)pyridone and physiologically tolerable salts thereof; polyacrylic acid polymer; sodium dioctylsulfosuccinate; and 2-octyldodecanol; wherein the composition is not an emulsion.

As per terms of settlement, Glenmark will have a license to launch a generic version of Ciclopirox Olamine (Loprox) 0.77% gel, supplied by Medicis immediately.

Also, Glenmark announced (in a press release Here ) that it has entered into an agreement with pharma giant Medicis Pharmaceuticals for co-development of dosage forms for the treatment of acne vulgaris.

Lansoprazole (Prevacid) ODT tablets: Teva Receives Favorable Court Decision; Innovator appeled in CAFC

Innovator Takeda has appealed against the U.S. District Court for the District of Delaware decision, wherein, court found no infringement by Teva in a patent dispute on Lansoprazole (Prevacid) ODT tablets.

Earlier, generic player Teva Pharma announced (in a press release Here ) that the U.S. District Court for the District of Delaware has issued a decision in its litigation over the Company's Abbreviated New Drug Application (ANDA) to market its generic version of Takeda Pharmaceuticals North America, Inc.'s Prevacid® (Lansoprazole) SoluTab.

The Court found that Teva's generic Lansoprazole orally disintegrating tablets do not infringe the following disputed patent:

US5464632 (Assignee: Laboratoires Prographarm ; Date of Filing: November 29, 1994; Date of expiry: May 7, 2013) The patent covers a rapidly disintegratable tablet for oral administration with or without the use of water, said tablet comprising an active substance and a mixture of excipients, wherein said active substance is multiparticulate and in the form of coated microcrystals, coated microgranules or uncoated microgranules and wherein said mixture of excipients comprises excipients which are responsible for the disintegration, said tablet being intended to be swallowed said disintegration occurring in less than sixty seconds under the action of the excipients which are responsible for the disintegration and which are selected from the group consisting at least one disintegrating agent and at least one swelling agent.

To overcome above claim, Teva used Starlac (a coprocessed excipients with 85% of Lactose and 15% of corn starch). The generic company and innovator provided testimony in the court w.r.t mechanism of disintegration of Starlac, however, opposing party could not prove convincingly that either lactose or corn starch was responsible for the rapid disintegration of generic product. In the light of above findings, court concluded that Teva’s generic version would not be covered under the scope of ‘632 patent.

As per press release, Teva intends to complete an analysis of the decision before deciding upon its next course of action.

Annual sales of the brand product were approximately $500 million in the United States for the twelve months that ended June 30, 2009 based on IMS sales data.

New Paragraph IV certifications reported by USFDA From Oct, 2009 to 5th November, 2009

1) Diclofenac Sodium and Misoprostol (Arthrotec) 50 mg + 0.2 mg DR Tablets : Paragraph IV filed on June 29, 2009

2) Fluvoxamine Maleate 100 mg Capsules (Luvox CR) 5 mg ad 10 mg Tablets: Para IV filed on April 20, 2009

3) Glycopyrrolate (Robinul Forte) 1.5 mg Tablets : Para IV filed on May 6, 2009

4) Vardenafil (Levitra) 5 mg ad 10 mg Tablets: Para IV filed on July 10, 2009

5) Amoxicillin and Clavulanate Potassium (Augmentin XR) 1000 mg + 62.5 mg ER tablets : Para IV filed on Jan 21, 2009

6) Armodafinil (Nuvigil) 50 mg, 150 mg and 250 mg: Para IV filed on July 24, 2009; for the other stregths like 100 mg and 200 mg, Para IV filed on Sep 11, 2009

7) Atazanavir Sulfate (Reyataz) 300 mg Capsules: Para IV filed on July 20, 2009

8) Caspofungin Acetate (Cancidas) 50 mg and 70 mg vial for injection: Para IV filed on June 26, 2009

9) Cisatracurium Besylate (Nimbex) 2 mg/mL, 5 mL vial and 10 mg/mL, 20 mL vial: Para IV filed on Aug 4, 2009; 2 mg/mL, 10 mL vial Para IV filed on Aug 12, 2009

10) Ezetimibe and Simvastatin (Vytorin) 10 mg + 10 mg, 10 mg + 20 mg, 10 mg + 40 mg and 10 mg + 80 mg Tablets: Para IV filed on July 27, 2009

11) Olopatadine Hydrochloride (Patanase) 0.665 mg/Spray (Nasal Spray): Para IV filed on June 29, 2009

12) Metformin Hydrochloride (Glumetza) 500 mg and 1000 mg ER tablets: Para IV filed on July 27, 2009

13) Mometasone Furoate (Nasonex ) 50 mcg/nasal spray: Para IV filed on Aug 7, 2009

14) Morphine Sulfate (Avinza) 45 mg and 75 mg ER capsules: Para IV filed on July 30, 2009

15) Ramelteon 8 mg Tablets (Rozerem): Para IV filed on July 22, 2009

16) Sibutramine Hydrochloride (Meridia) 10 mg and 15 mg: Para IV filed on Aug 14, 2009

17) Tigecycline (Tygacil) For Injection 50 mg per vial: Para IV filed on June 15, 2009

18) Tobramycin (Tobi) 300 mg/5 ml Inhalation Solution: Para IV filed on June 29, 2009

19) Linezolid (Zyvox) 100 mg/5 ml Oral Suspension: Para IV filed on Aug 3, 2009

Source: USFDA Para IV list Here

Ramelteon (Rozerem) 8 mg Tablets: Innovator Takeda Sues Teva

In an attempt to block generic version of Ramelteon (Rozerem) 8 mg Tablets, innovator Takeda has filed an infringement action against generic player Teva pharma in U.S. District Court for the District of Delaware.

Innovator has listed following patent in the Orange Book for this product:

US6034239 (Expiry: Mar 6, 2017): The patent covers Ramelteon as product

The generic player Teva has challenged the said patent on various patent invalidation grounds.

Earlier, innovator got approval to market Ramelteon (Rozerem) 8 mg Tablets on Jul 22, 2005.

Recent press releases: Brimonidine tartrate, Fenofibrate, Glatiramer acetate, Lansoprazole

Brimonidine tartrate ophthalmic solution 0.1% and 0.15% (ALPHAGAN): Innovator announced favorable decision by US court

Innovator Allergan announced (in a press release Here ) that the United States District Court for the District of Delaware has ruled in favor of Allergan on key patents covering Brimonidine tartrate ophthalmic solution 0.1% and 0.15% (ALPHAGAN). The court has upheld the validity of key patents US6627210; US6641834; US6673337; US6562873; and US5424078

Fenofibrate (Tricor) 48 mg and 145 mg Tablets: Impax Laboratories Confirms Patent Challenge

Generic player Impax Laboratories confirmed ( in a press release Here) that it has initiated a challenge of the patents listed by Abbott Laboratories in connection with Fenofibrate (Tricor) 48 mg and 145 mg Tablets.

Glatiramer acetate injection (Copaxone):Teva asserts 3 more patents against generic players Monenta/Sandoz

Innovator Teva Pharma announced (in a press release Here) it is seeking to amend its existing complaint against Momenta Pharmaceuticals, Inc./Sandoz Inc. to include patent infringement of three additional patents related to the characterization of Glatiramer acetate injection (Copaxone). The proposed updated complaint has been filed under seal with the U.S. District Court for the Southern District of New York along with a motion requesting that the Court grant Teva leave to amend.

Lansoprazole (Prevacid) Delayed-Release Capsules 15 mg and 30 mg: Teva got final approval
Generic player Teva Pharma announced (in a press release Here) today that the U.S. Food and Drug Administration has granted final approval for the Company's Abbreviated New Drug Application (ANDA) to market its generic version of Tap Pharmaceutical's proton pump inhibitor Lansoprazole (Prevacid) Delayed-Release Capsules 15 mg and 30 mg. Customers will begin receiving product on November 11, 2009. Annual sales of Prevacid® Delayed-Release Capsules were approximately $2.97 billion in the United States for the twelve months that ended June 30, 2009 based on IMS sales data

Armodafinil 50 mg, 100 mg, 150 mg, 200 mg and 250 mg Tablets (Nuvigil): Innovator confirmed receipt of Para IV notice letter from Teva

Innovator company Cephalon announced (in a press release Here ) that they have received Paragraph IV certification letter from generic player Teva Pharma on October 20, 2009, wherein, Teva has informed innovator that they have filed ANDA with Paragraph IV certification against some selected Orange Book listed patents for Armodafinil 50 mg, 100 mg, 150 mg, 200 mg and 250 mg Tablets (Nuvigil).

Following Patents are listed in Orange Book for Armodafinil 50 mg, 100 mg, 150 mg, 200 mg and 250 mg Tablets (Nuvigil):

US4927855 (Assignee: Laboratoire L. Lafon; Expiry: Oct 22, 2010): Which covers (-)-Benzhydrylsulfinylacetamide and derivatives as product

US7132570 (Assignee: Cephalon France; Expiry: Jun 18, 2024): The said patent covers crystalline polymorphic form I of Armodafinil

US7297346 (Assignee: Cephalon Inc; Expiry: May 29, 2024): Which covers a pharmaceutical composition of Armodafinil

USRE37516 (Assignee: Cephalon, Inc; Expiry: Apr 6, 2015): Which covers particle size of Armodafinil

As per press release, Teva has filed ANDA with Paragraph IV certification against ‘570, ‘346 and ‘516 patents. Importantly, Teva has not challenged compound patent '855.

Armodafinil, which is chemically, (–)-2-[(R)-(diphenylmethyl)sulfinyl]acetamide improves wakfulness and used as stimulant agent in the treatment of hypersomnia.

Olmesartan (Benicar), Olmesartan+Hydrochlorthiazide (Benicar HCT) and Olmesartan+ Amlodipine (AZOR) formulations: Innovator got Pediatric exclusivity

Innovator Daiichi has got 6 months pediatric exclusivity for Olmesartan and it's combination products in US market.

The Orange Book patents would expire on following revised dates:

US5616599 (Expiry:Oct 25, 2016): Which covers Olmesartan as product

US6878703 (Expiry:May 19, 2022): which covers combination of Olmesartan with HCTZ

In the light of above extension, the generic version would be delayed by 6 months.

The generic for Olmesartan tablets (Benicar) would be expected after Oct 25, 2016.

The generic version for Olmesartan+ Amlodipine (AZOR) formulations would be expected after Oct 25, 2016.

Further, Olmesartan+Hydrochlorthiazide (Benicar HCT) would be expected after May 19, 2022

Glatiramer acetate 20 mg/ml injection (Copaxone): Teva sued Mylan

Refer to our earlier post Here, wherein, we reported the ANDA filing by generic player Mylan (with Para IV certification) against Glatiramer acetate 20 mg/ml injection (Copaxone).

As expected, innovator Teva has reported Here that it has filed a lawsuit against Mylan Pharma and it's API supplier Natco Pharma for patent infringement in the U.S. District Court for the Southern District of New York.

Innovator Teva has listed US5981589, US6054430, US6342476, US6362161, US6620847, US6939539 and US7199098 patents in Orange Book for Glatiramer acetate 20 mg/ml injection (Copaxone). The said patents would expire on May 24, 2014. As per complaint filed in in the U.S. District Court for the Southern District of New York, Teva has requested court to block the generic version’s approval till May 24, 2014.

Earlier, innovator has sued generic players Momenta and Sandoz in U.S. District Court for the Southern District of New York for filing ANDA in Jul, 2008.

Pharma news

Clindamycin phosphate (1%) and Benzoyl peroxide (5%) gel (Duac®Gel): perrigo announced settlement with innovator

Generic player Perrigo has settled pending litigation with innovator Stiefel Laboratories (a division of Glaxo SmithKline) on Clindamycin phosphate (1%) and Benzoyl peroxide (5%) gel (Duac®Gel). Eralier, perrigo purchased the ANDA (as reported by Perrigo Here ) for this product from first para IV filer KV pharma.

Lilly to Sell Tippecanoe Manufacturing Site to Evonik Industries
Pharma Giant Eli Lilly and Company announced (in a press release Here ) the sale of its Tippecanoe Laboratories manufacturing facility to Evonik Industries AG, one of the world's largest chemical companies

Update on Oct 22, 2009

Dr. Suresh Pillai of Patent docs has reviewed the following interesting cases:

1) Escitalopram (Lexapro)

2) Memantine (Namenda)

3) Moxifloxacin (Vigamox)

For details, please check following link:

http://www.patentdocs.org/2009/10/biotech-2.html

Voriconazole 50 mg and 200 mg Tablets (Vfend): Pfizer announced settlement and licensing agreement with Mylan

Innovator Pfizer announced (in a press release Here) that it has entered into an agreement with generic player Mylan relating to a generic version of antifungal formulation Vfend (Voriconazole: (2R,3S)-2-(2,4-difluorophenyl)-3- (5-fluoropyrimidin-4-yl)-1- (1H-1,2,4-triazol-1-yl) butan-2- ol) 50 mg and 200 mg tablets. The agreement is limited to the tablet form of Voriconazole and does not cover Pfizer’s Voriconazole products for intravenous use or oral suspension.

The following patents are listed in Orange Book:

US5116844 (Expiry: Aug 11, 2009): which covers composition

US5364938 (Expiry: Nov 15, 2011): Covers Voriconazole generically

US5567817 (Expiry: May 24, 2016): Covers Voriconazole specifically

US5773443 (Expiry: Jan 25, 2011): Covers Voriconazole generically

Earlier, first Para IV filer, Matrix submitted its ANDA on April 14, 2008, as reported earlier by IP Pharma Doc Here. Importantly, Pfizer did not file a lawsuit against Matrix within the 45-day time period provided by the Hatch-Waxman Act to initiate an automatic stay of regulatory approval.

Voriconazole 50 mg and 200 mgTablets (Vfend) was approved by USFDA on May 24, 2002.
Pursuant to the agreement, Mylan will have the right to market voriconazole tablets in the United States in the first quarter of 2011. Additional details of the agreement with Mylan remain confidential. The agreement is subject to review by the U.S. Department of Justice and the Federal Trade Commission.

Amophetamine salts (ADDERALL XR) 5, 10, 15, 20, 25 and 30 mg ER Capsules: Shire and Sandoz Settled patent litigation

Innovator Shire, announced (in a press release Here ) that it has settled the pending patent litigation with generic player Sandoz on generic versions of Shire’s ADDERALL XR (mixed amphetamine salts like AMPHETAMINE ASPARTATE; AMPHETAMINE SULFATE; DEXTROAMPHETAMINE SACCHARATE; DEXTROAMPHETAMINE SULFATE) for the treatment of Attention Deficit Hyperactivity Disorder.

The following patents are listed in Orange Book for this product:

US6322819 (Assignee: Shire Laboratories; Date of Grant: November 27, 2001; Expiry: Apr 21, 2019): which covers a pharmaceutical composition for delivery of one or more pharmaceutically active amphetamine salts, comprising: (a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating; and (b) one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release.

US6605300 (Assignee: Shire Laboratories; Date of Grant: August 12, 2003; Expiry: Apr 21, 2019): A pharmaceutical formulation for delivery of a mixture of amphetamine base salts effective to treat ADHD in a human patient comprising: an immediate release dosage form that provides immediate release upon oral administration to said patient; a delayed enteric release dosage form that provides delayed release upon oral administration to said patient; and a pharmaceutically acceptable carrier; wherein said amphetamine base salts comprise dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate and amphetamine sulfate; wherein said pharmaceutical formulation is sufficient to maintain an effective level of amphetamine base salts in the patient over the course of at least 8 hours without further administration of amphetamine base salt, and the peak plasma concentration of amphetamine base salts reached after release of said delayed enteric release dosage form exceeds the peak plasma concentration previously reached after release of said immediate release dosage form; and wherein said pharmaceutical formulation, when containing about a total dose of 20 mg, will produce in a human individual a plasma concentration versus time curve (ng/ml versus hours) having an area under the curve (AUC) of about 467 to about 714 ng hr/ml.


The generic player Sandoz challenged Orange Book patents in 2007, subsequently, innovator sued Sandoz in Colorodo District Court.

As part of the settlement, Sandoz has agreed to a consent judgment confirming that its proposed generic products infringe Shire’s ’819 and ’300 Patents and that the two patents are valid and enforceable. Also as per press release, resolution of the case against Sandoz ends all pending litigation against generic ANDA applicants over ADDERALL XR. As per press release, the US Federal Trade Commission (FTC) would review the said agreement.


The settlement also provides Sandoz with a license to market it own generic versions of ADDERALL XR in the United States beginning upon approval of its own generic products by the USFDA and Sandoz will pay Shire a royalty from those sales. Also, no payments to Sandoz are involved in the settlement agreement. Impax Pharmaceuticals Inc. and Barr Laboratories Inc. remains the only authorized generic supplier of ADDERALL XR.


Earlier, innovator Shire got approval to market this combination product on Oct 11, 2001 (30, 20 and 10 mg Capsules) and on May 22, 2002 (15, 5 and 25 mg capsules)

New Paragraph IV certifications reported by USFDA from Sep 8, 2009 to Oct 8, 2009

1) Mycophenolic Acid (Myfortic) 180 mg Delayed-release Tablets: Para IV filed on June 4, 2009

2) Nisoldipine (Sular ) 8.5 mg and 17 mg Extended-release Tablets: Para IV filed on March 2, 2009

3) Telmisartan and Hydrochlorothiazide (Micardis HCT) 80 mg+25 mg Tablets: Para IV filed on Feb 27, 2009

4) Tramadol Hydrochloride (Ryzolt )100 mg, 200 mg and 300 mg ER Tablets: Para IV filed on June 18, 2009

5) Carbidopa, Levodopa and Entacapone (Stalevo 75 and Stalevo 125) Tablets: Para IV filed on May 19, 2009

6) Ephinephrine (Epipen) Injection: Para IV filed on Nov 21, 2008

7) Docetaxel (Taxotere) Injection 40mg/mL, 0.5mL and 2mL vials: Para IV filed on June 30, 2009

8) Piperacillin and Tazobactam (Zosyn) For Injection 2.25 g/vial, 3.375 g/vial, 4.5 g/vial: Para IV filed before Feb 5, 2009

9) Repaglinide and Metformin (Prandimet) 1 mg + 500 mg and 2 mg + 500 mg Tablets : Para IV filed on April 9, 2009

Source: USFDA website Here

Continuation patent Applications: USPTO and GSK settled patent litigation

The United States Patent and Trademark Office (USPTO) announced (in a press release Here ) that it has filed a joint motion with pharma giant GlaxoSmithKline (GSK) to dismiss the lawsuit related to continuation rules.

Background of the case

Earlier in August 2007, The USPTO published new rules to improve patent prosecution and examination. However, contentious rules on Final Rule 114 (requests for continued examination), Final Rule 75 (claims), and Final Rule 265 (examination support documents) were opposed.

After the said notification, an inventor Dr. Triantafyllos Tafas and GSK (and others) opposed said rule and filed complaint in U.S. District Court of the Eastern District of Virginia. Later in April, 2008 the district court sided with GSK, subsequently, USPTO appealed against said decision in U.S. Court of Appeals for the Federal Circuit (CAFC).

On March 20, 2009, the CAFC issued a decision addressing:
a) whether the Claims and Continuation Final Rules fall within the scope of the USPTO’s rulemaking authority and
b) whether the Final Rules are contrary to the Patent Act.

The Court opined that the Final Rules were all within the agency’s rulemaking authority. The Court also concluded that Final Rule 114 (requests for continued examination), Final Rule 75 (claims), and Final Rule 265 (examination support documents) are consistent with the Patent Act, but that Final Rule 78 (continuations) violates the Patent Act. The Court remanded several issues to the district court.

In 2009, the Federal Circuit granted rehearing en banc, and ordered additional briefing that would have commenced in the coming weeks.

Atorvastatin + Amlodipine Tablets (Caudet): Pfizer sued Sandoz for filing ANDA with Para IV certification

Innovator Pfizer has initiated patent infringement proceedings against generic player Sandoz for filing ANDA with Para IV certification against Orange Book listed patents on Atorvastatin + Amlodipine Besylate (Caudet) Tablets (80+5 mg and 80+10 mg tablets) in the U.S. District Court for the District of Delaware.

Earlier, the generic player Sandoz send Para IV notice letter to innovator on August 24, 2009, subsequently, innovator sued generic player on Oct 6, 2009 in U.S. District Court for the District of Delaware

Following patents are listed in Orange Book for Atorvastatin + Amlodipine Besylate (Caudet) Tablets:

US4681893 (Expiry: 24 March, 2010)- Covers racemic form of Atorvastatin generically.

USRE40667/ US5273995 (Expiry: 28th June, 2011)- Covers Atorvastatin enantiomer and salts as Product (Specifically)

US5686104 (Expiry: 11th May, 2015)- Covers stable Formulation

US5969156 (Expiry: 8th June, 2017)- Polymorph (Form I, II and IV)

US6126971 (Expiry: 19th July, 2013)- Covers stable formulation

US6455574 (Expiry: Aug 11, 2018)- Which covers combination of Atorvastatin + Amlodipine

As per complaint, innovator has sued generic player for the infringement of ‘574 patent.

Probably, Sandoz has filed Para IV with invalidation grounds against ‘574 patent.

Atorvastatin + Amlodipine Besylate (caudet) combination is indicated for the treatment of hypertension and hyperlipidemia

Galantamine tablets (Razadyne): CAFC declared method of use patent invalid due to lack of enablement and utility

The Court of Appeal for Federal Circuit (CAFC) bench of Circuit Judges Mayer, Gajarsa, and Dyk (with dissent from Gajarsa) in 2-1 decision has upheld the U.S. District Court of Delaware’s decision (as detailed by this blog Here ) that innovator ORTHO MCNEIL JANSSEN’s key patent on Galantamine was invalid because of lack of enablement under 35 USC 112, lack of utility under 35 USC 101.

The various generic players like Teva, Barr, Mylan, Dr. Reddy, Purepac, Alpharma opposed innovator’s following patent:

US4663318 (Expiry: Dec 14, 2008): Which covers method of treating Alzheimer's disease and related dementias which comprises administering to a patient suffering from such a disease a therapeutically effective amount of Galanthamine or a pharmaceutically-acceptable acid addition salt thereof.

Innovator has listed the said patent for Galantamine tablets (Razadyne) 4 mg, 8 mg and 12 mg tablets and Galantamine tablets (Razadyne ER) 8 mg, 16 mg and 24 mg extended release capsules

The court opined the patent covers an abstract idea only, without sufficient details on how a person having ordinary skilled in the art can use the invention. Also, the specification (which is of 1 page only) does not disclose full utility of the invention and there is no information about dosage forms to be used for the prevention of Alzheimer’s disease.

Galantamine is used for the treatment of mild to moderate Alzheimer’s disease and various memory impairments. Galantamine is a competitive and reversible cholinesterase inhibitor. It is believed it works by enhancing cholinergic function by increasing the concentration of acetylcholine in the brain.

The increased concentration of acetylcholine is directly linked to memory enhancement. The inventor of the patent Dr. Davies identified this fact and correlated the use of Galantamine with Alzheimer’s disease; however, at the time of filing of patent application, the test data to validate the same fact was not ready.

The CAFC opinion Here

Quetiapine fumarate (Seroquel): CAFC upholds the validity of key patent

Innovator AstraZeneca announced (in a press release Here ) that the US Court of Appeals for the Federal Circuit has affirmed the Summary Judgment decision of No Inequitable Conduct in patent litigation involving Seroquel (quetiapine fumarate) tablets.

Earlier in July 2008, the US District Court for the District of New Jersey granted the company's Motion for Summary Judgment of No Inequitable Conduct during prosecution of key patent US4879288 (Expiry: March, 2012), which covers Quetiapine as product.

In a separate press release Here generic player Teva pharma announced that, Teva expects to market its generic version of AstraZeneca's antipsychotic agent Seroquel® (Quetiapine Fumarate) Tablets no later than March 2012, when the patent is otherwise set to expire.

Earlier, generic players Teva and Sandoz challenged ‘288 by filing Para IV against said patent with invalidation grounds. Also, generic players alleged that innovator during prosecution of ‘288 patent had not disclosed test data on the closely related compounds to USPTO.

The generic players alleged that the said data would have been material to the patentability of ‘288 patent. The CAFC affirmed US District Court for the District of New Jersey decision that there wasn’t sufficient evidence which can clearly show that during prosecution of ‘288 patent application in the USPTO, innovator Astra Zeneca made a misrepresentation of material fact or an omission of material fact to the USPTO, with intent to deceive or mislead the patent examiner into granting the patent.

The CAFC opinion Here

Piperacillin and Tazobactam for Injection: Orchid got USFDA approval with 180 days exclusivity; District court refused TRO against generic version

Indian generic player Orchid Pharmaceuticals announced in a press release Here that company has received final approval from US regulatory authority USFDA to market Piperacillin and Tazobactam for Injection’s generic equivalents in 2.25 g, 3.375 g and 4.5 g vial as well as 40.5 g (Pharmacy Bulk Package) dosage forms and strengths. Importantly, Orchid has further confirmed that they have received 180 days first to file generic exclusivity for this important product.

Innovator’s Request for Temporary Restraining Order

Subsequently, in an attempt to block generic launch, innovator Wyeth filed a suit in the US District Court of Columbia against the USFDA relating to the agency's approval of Orchid's ANDAs for its generic products, Piperacillin and Tazobactam for Injections and also against the FDA's decision on Wyeth's Citizen Petition.

US court denied Temporary Restraining Order
On September 24, 2009, the US District Court for the District of Columbia denied Wyeth Pharmaceutical's motion for a Temporary Restraining Order (TRO). Wyeth's request for TRO was filed in connection with its lawsuit against the US FDA challenging the US FDA's approval of Orchid's ANDAs for its generic products, Piperacillin and Tazobactam for Injections. The Court rejected Wyeth's requests and denied the TRO.

In its Memorandum Opinion and Order, the Court found that "Wyeth has failed to demonstrate a likelihood of success on the merits" of its claim that the US FDA's approval of Orchid's ANDAs violated applicable US statutes.

Orchid is pleased with this result and will continue to protect its approved ANDAs for its Piperacillin and Tazobactam for Injections and also continue to supply the products to its distribution partner, Apotex Corp., for marketing and distribution in the US.

Source: http://www.orchidpharma.com/

Solifenacin Succinate (Vesicare) 5 and 10 mg tablets: Innovator Astellas sued Teva for filing ANDA with Para IV certification

Japanese pharma giant M/S Astellas Pharma announced (in a press release Here ) that they have initiated the patent infringement action against generic pharma gaint M/S Teva pharma in United States District Court, Southern District of New York on September 22, 2009.

Following patent is listed in the Orange Book for Solifenacin Succinate (Vesicare) 5 and 10 mg tablets:

US6017927 (Assignee: Yamanouchi Pharmaceutical; Date of Expiry: Nov 19, 2018): The patent covers quinuclidine derivatives or their salts, or quaternary ammonium salts having muscarinic receptor antagonistic activities and also to pharmaceutical compositions containing such compounds. The patent covers Solifenacin as product.

Solifenacin Succinate (Vesicare) tablets are prescribed for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and urinary frequency.

Innvator Asttelas has been marketing Solifenacin Succinate (Vesicare) 5 and 10 mg tablets, since Nov 19, 2004

Raloxifene Hydrochloride (Evista) 60 mg Tablets: District court upheld the validity of MOU patents; particle size patent declared invalid

Innovator Eli Lilly announced (in a press release Here ) that in a patent dispute with generic player Teva Pharma, the U.S. District Court for the Southern District of Indiana has upheld Eli Lilly and Company's method-of-use patents on Raloxifene Hydrochloride (Evista) 60 mg Tablets. The method of use patents provide patent protection for Raloxifene Hydrochloride (Evista) 60 mg tablets till March, 2014.

In addition, the Court held innovator Eli Lilly's Raloxifene Hydrochloride (Evista) 60 mg Tablets patents on particle-size, US6458811 (Expiry: Mar 10, 2017) and US6894064 (Expiry:Mar 10, 2017) as invalid. The court opined that generic player Teva has proved by clear and convincing grounds that the said patents are invalid due to lack of enablement under 35 USC 112. Further, court opined that description of the patent is not clear on partcle size evaluation in the formulations.

Background of patent litigation

Teva filed its Para IV certification against Following Orange Book listed patents

US5393763 (Expiry: Jul 28, 2012); which covers a method of inhibiting bone loss

US6906086 (Expiry: Jul 28, 2012); which covers a method of inhibiting post-menopausal bone loss in a post-menopausal woman in need of treatment to prevent or treat post-menopausal osteoporosis comprising administering a single daily oral dose to said woman of an effective amount of 6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl-4-[2-(piperidin-1-yl)ethox yphenyl]methanone hydrochloride.

USRE38968 (Expiry: Jul 28, 2012); which covers method of use in a post-menopausal woman in need of treatment to prevent or treat post-menopausal osteoporosis by use of Raloxifen

USRE39049 (Expiry: Jul 28, 2012); which covers method of use in a post-menopausal woman in need of treatment to prevent or treat post-menopausal osteoporosis by use of Raloxifen

USRE39050 (Expiry:Mar 2, 2014); which covers a method of inhibiting bone loss or resorption, or lowering serum cholesterol, comprising administering to a human in need thereof Raloxifen

US5478847 (Expiry:Mar 2, 2014); which covers a method of inhibiting bone loss or bone resorption comprising administering to a human in need thereof a Raloxifen, in an amount of about 50 to 150 mg/day.

US5457117 (Expiry: Jul 28, 2012); which covers a method of inhibiting bone loss comprising administering to a human in need thereof an effective amount of 6-hydroxy-2-(4-hydroxyphenyl)-benzo[B]thien-3-yl-4-[2-(piperidin-1-yl)etho xyphenyl]methanone hydrochloride.

US5393763 (Expiry: Jul 28, 2012); which covers a method of inhibiting bone loss or resorption, or lowering serum cholesterol, comprising administering to a human in need thereof Raloxifen

US5811120 (Expiry:Mar 2, 2014); which covers a solid administerable pharmaceutical formulation comprising raloxifene hydrochloride in combination with a surfactant, polyvinylpyrrolidone, and a water soluble diluent, wherein: the surfactant is a sorbitan fatty acid ester or a polyoxvethylene sorbitan fatty acid ester; and the water soluble diluent is a polyol or sugar.

US5972383 (Expiry:Mar 2, 2014); which covers a method of treating mammary tumors, prostatic tumors, or osteoporosis, comprising administering to a human in need thereof a solid orally administerable pharmaceutical formulation comprising raloxifene hydrochloride in combination with a surfactant, polyvinylpyrrolidone, and a water soluble diluent, wherein: the surfactant is a sorbitan fatty acid ester or a polyoxyethylene sorbitan fatty acid ester; and the water soluble diluent is a polyol or sugar.

US6894064 (Expiry:Mar 10, 2017); which covers a pharmaceutical composition comprising: a) 60 mg of 6-hydroxy-2-(4-hydroxy-phenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]th iophene hydrochloride, characterized in that the benzo[b]thiophene compound is in particulate form, said particles having a mean particle size of less than about 25 microns, at least about 90% of said particles have a size of less than about 50 microns; b) a surfactant; and c) a water-soluble diluent.

US6458811 (Expiry:Mar 10, 2017); which covers Raloxifen in particulate form, said particles having a mean particle size of less than about 25 microns, at least about 90% of said particles have a size of less than about 50 microns.

US6797719 (Expiry:Mar 10, 2017): which covers Raloxifen in particulate form, said particles having a mean particle size of less than about 25 microns, at least about 90% of said particles have a size of less than about 50 microns; b) a surfactant; and c) a water-soluble diluent.

Innovator sued Teva (within 45 days of Para IV notice from Teva) in Indiana Southern District Court in June, 2006 for infringement of method of use patents (Innovator not sued Teva on ‘064, '819 ,‘719 ), accordingly, Teva 's ANDA approval was delayed by 30 months.

Additionally, innovator also sued Teva for following patents not listed in Orange Book:

US5747510 (Expiry:Mar 2, 2014); A pharmaceutical formulation in daily dosage unit form comprising, per daily dosage unit, an amount within the range of about 55 to about 150 mg of Raloxifen or a pharmaceutically acceptable salt or solvate thereof, said formulation in dosage unit form being adapted for oral administration in the form of a capsule or tablet.

US5641790 (Expiry:Jun 24, 2014); A pharmacuetical formulation in dosage unit form comprising per dosage unit, an amount within the range of about 55 to about 150 mg of a Raloxifen or a pharmaceutically acceptable salt or solvate thereof.

The CAFC decision on ANDA approval of Teva Pharma:
Earlier, Innovator Eli Lilly got a favorable decision from Court of Appeal for federal Circuit (CAFC) on Feb 24, 2009 w.r.t Raloxifene Hydrochloride 60 mg Tablets. CAFC has delayed Teva’s ANDA approval by 6 months. The Chief Judge Rader and Michel affirmed a district court order (by 2-1, with dissent from fellow Judge Prost)) extending the thirty-month stay of USA approval of Teva's ANDA.
Court Opinion Here

Preliminary Injunction Opinion on “at risk launch” by Teva Pharma:
In April, 2009, innovator Eli Lilly announced (in a press release Here) that the U.S. District Court for the Southern District of Indiana has issued a preliminary injunction to prevent “at risk launch” of a generic version of Lilly's medicine Raloxifene Hydrochloride (Evista) 60 mg Tablets by Teva until the Court renders its final ruling. Earlier, Teva had indicated it was prepared to launch the generic version prior to the resolution of outstanding patent litigation currently being considered by the U.S. District Court for the Southern District of Indiana. Lilly had previously sought and been granted a temporary restraining order to prevent the generic launch.

Conclusion: Innovator succeded in establishing validity of method of use patents in District court, the said protection would be effective till 2014. In a partial viactory for generic player, Teva has been able to cut the patent protection of Raloxifene by almost 3 year. Also, both the parties can appeal against the said decision in higher court.

Doxycycline 40 mg DR capsules (Oracea): Impax Labs Confirmed Patent Challenge

Generic player Impax Lab confirmed (in a press release Here ) that it has initiated a Paragraph IV patent challenge to patents listed in the Orange book by innovator M/S Galderma Labs for Doxycycline 40 mg DR capsules (Oracea).

Following patents are listed in Orange Book for Doxycycline 40 mg DR capsules (Oracea):

US5789395 (Expiry: Aug 30, 2016): Which covers a method for inhibiting nitric oxide production in a mammal system, comprising providing to the mammalian system an amount of a tetracycline compound sufficient to cause a decrease in the amount of nitric oxide produced endogenously by the mammalian-system.

US5919775 (Expiry: Aug 30, 2016): Which covers a method of inhibiting expression of inducible nitric oxide synthase in a mammal system, comprising administering to said mammal system an amount of a tetracycline compound sufficient to inhibit inducible nitric oxide synthase expression in said mammal system

US7211267 (Expiry: Apr 5, 2022): Which covers a method of treating acne in a human in need thereof comprising administering orally or intravenously to said human an antibiotic tetracycline compound in a sub-antibacterial amount that reduces lesion count, said amount being 10 80% of the antibacterial effective amount, wherein the tetracycline compound is administered long term, without administering a bisphosphonate compound.

US7232572 (Expiry: Apr 5, 2022): Which covers a method for treating papules and pustules of rosacea in a human in need thereof comprising administering orally to said human a tetracycline compound, or a pharmaceutically acceptable salt thereof, in an amount that is effective to treat the papules and pustules of rosacea, but has substantially no antibiotic activity, said amount being 10-80% of the antibiotic amount, wherein the tetracycline compound is an antibiotic tetracycline compound or a pharmaceutically acceptable salt thereof administered in an amount that results in no reduction of skin microflora during a six-month treatment, without administering a bisphosphonate compound.

The ’775 and ‘267 patents are assigned to The Research Foundation of State University of New York (Albany, NY) and Hospital for Joint Diseases (New York, NY). The ‘267 and ‘572 patents are assigned to CollaGenex Pharmaceuticals. Innovator has licensing agreement with the assignees of these patents.

After the receipt of Paragraph IV notice letter of Impax by innovator, subsequently, on September 18, 2009, the assignee of the patent/innovator filed suit for patent infringement against generic player Impax in the United States District Court for the District of Delaware.

Earlier, in July, 2009, Indian generic player Lupin was sued by innovator for filing ANDA with Para IV certification for this product

Innovator GALDERMA LABS got approval from USFDA to market this product on May 26, 2006.

Doxycycline 40 mg DR capsules (Oracea) is indicated for the treatment of inflammatory lesions (papules and pustules) of rosacea in adult patients. According to Wolters Kluwer Health, U.S. sales of Doxycycline 40 mg DR capsules (Oracea) were approximately $104 million for the twelve-month period ending July 2009.

Glatiramer acetate 20 mg/ml injection (Copaxone): USFDA accepts Mylan’s ANDA for filing

The generic player M/S Mylan announced ( in a press release Here) that the U.S. Food and Drug Administration (FDA) has accepted for filing of Mylan Pharma's abbreviated new drug application (ANDA) for Glatiramer Acetate Injection (20 mg/ml), which is a generic version of innovator M/S Teva Pharma’s Glatiramer acetate injection (Copaxone). Glatiramer acetate injection (Copaxone) is indicated for the treatment of multiple sclerosis.

Also, Mylan entered into a license and supply agreement with Hyderabad based M/S NATCO Pharma which granted Mylan exclusive distribution rights for Glatiramer Acetate pre-filled syringes in the U.S. and all major markets in Europe, Australia, New Zealand, Japan and Canada. The agreement also includes an option to potentially expand into additional territories.

Earlier, in Jul, 2008, the generic player Sandoz (Momenta), a subsidiary of M/S Mylan filed ANDA for this product. Subsequently, in Aug, 2008, innovator sued the generic players in New York Southern District Court. As per complained filed against generic players, Teva opposed any generic version before patent expiry in May 24, 2014. (As detailed in our previous post Here )

Additionally, Teva filed a Citizen Petition on September 8, 2008 with the USFDA, wherein, Teva opined that designing around against this formulation would be extremely difficult and presents a significant challenge. Also, once injected, it is rapidly hydrolyzed locally and no level of the intact drug can be measured in the blood, rendering a bioequivalence study comparing two formulations extremely difficult.

Arguably, the mechanism of the drug product is not fully clear. Also, Innovator Teva requested in the citizen petition that generic players should carry out detailed clainical studies to establish quality, safety and efficacy of the generic product. Alternatively, Teva suggested USFDA that ANDA on Copaxone should be reviewed under 505 (b) (2) category.

In response to the citizen petition, USFDA refused to review the Citizen petition and communicated Teva that as ANDA review process is stayed till 30 months, it would be premature and inappropriate to address points raised by Teva before actual ANDA review process begins. (As detailed in our previous post Here )

Memantine hydrochloride (Namenda) 5 mg and 10 mg tablets: 4 generic players exit patent litigation

The chief judge honorable G.M. Sleet of U.S. District Court for the District of Delaware has signed off on a request to dismiss M/S Upsher-Smith Lab (and 3 other generic players) from a patent infringement lawsuit that innovator Forest Labs and Merz Pharma brought to thwart the generic challenge to the Alzheimer's drug Memantine (Namenda) hydrochloride 5 mg and 10 mg tablets.

Innovator has listed following patent in Orange Book for Memantine hydrochloride 5 mg and 10 mg tablets:

US5061703 (Expiry: April 11, 2015): 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 Memantine.

The various generic players filed ANDA with para IV certification against ‘703 patent.

Subsequently, innovator sued various generic players for the infringement of ‘703 patent in U.S. District Court for the District of Delaware.

As per court’s order, M/S Upsher-Smith Lab (and 3 other generic players) can not launch generic version till expiry of ‘703 patent.

Donepezil (Aricept) 5 mg and 10 mg Tablets: The district court declined Teva’s request for DJ

The US district court for the district of New Jersey declined M/S Gate pharma’s declaratory judgment request of non-infringement against 4 patents listed by innovator for Donepezil (Aricept) 5 mg and 10 mg Tablets

Following patents are listed In the Orange book for 5 and 10 mg tablets of Donepezil hydropchloride:

US4895841 (Expiry: NOV 25, 2010)- Product patent

US5985864 (Expiry: DEC 30,2016)- Polymorph (Form-II, III, IV and V)

US6140321 (Expiry: DEC 30,2016)-polymorph

US6245911 (Expiry: DEC 01,2018)-Polymorph A, B and C

US6372760 (Expiry: MAR 31,2019)- Formulation

Ranbaxy filed (first para IV filer) ANDA with Para IV certification against ‘864, ‘321, ‘911, ‘760 and Para III against product patent ‘841.

Generic player Teva filed ANDA on Oct, 2004, with Para IV certification against ‘864, ‘321, ‘911, ‘760 and Para III against product patent ‘841. Later, in Oct, 2005, Teva amended it’s ANDA with Para IV against product patent ‘841. Due to Para IV filing against product patent, Teva also got First Filer status.

Also, in late 2005, a subsidiary of Teva, M/S Gate Pharma filed ANDA with different API of Donepezil, with Para III certification against all O.B Patents. However, after nearly two years, Gate amended it’s ANDA on Nov, 2007 with Para IV against all patents.

Subsequently, innovator sued Gate and Teva for the infringement of ‘841 and the district court found the patent valid, enforceable and issued preliminary injunction against generic launch, as reported by this blog Here.

After the said decision, with an aim to trigger Ranbaxy’s exclusivity (and Teva’s, too), the Gate filed DJ action of non-infringement, citing ANDA approval delay by USFDA. Further, innovator has already disclaimed ‘864 and ‘721 patents and for '911 and '760 patents innovator issued ‘convenant not to sue’ to Teva. In its opposing motion, innovator Esai contends that the court lacks subject matter jurisdiction because Teva’s claim for DJ present no justiciable controversy.
The US district court for the district of New Jersey declined Gate pharma’s declaratory judgment of non-infringement against ‘864, ‘321, ‘911 and ‘760.

The district court opined that M/S Teva did not risk a lawsuit from innovator Eisai or face the threat that the USFDA might block its ANDA approval process.

Earlier, Apotex has also filed DJ action of non-infringement against above 4 patents with an aim to trigger Ranbaxy’s 180 days exclusivity.

Nateglinide (Starilax) 60 mg and 120 mg tablets: 3 generic players got final approval from USFDA

The three generic players namely, Dr. Reddy, Par pharma and Teva Pharma has got final approval from USFDA on September 9, 2009 to market Nateglinide (Starilax) 60 mg and 120 mg tablets.

The generic launch was possible after the expiry of product patent USRE34878, which expired on Sep 8, 2009

Earlier, Innovator Novartis got final approval to market Nateglinide (Starilax) 60 mg and 120 mg tablets on December 22, 2000.

The approved generic versions are AB rated w.r.t Starilax tablets

Loestrin 24 Fe and Femcon Fe: Innovator sued Lupin for Para IV filing

Innovator M/S Warner Chilcott announced (in a press release Here ) that one of its subsidiaries has filed lawsuits against Indian generic player M/S Lupin Pharma in the District Court for the District of Delaware for infringement of Warner Chilcott's U.S. Patent Nos. 5,552,394 (Expiry: in July 2014) and 6,667,050 (Expiry April 2019), which cover oral contraceptives Loestrin 24 Fe (Norethindrone acetate and Ethinyl estradiol tablets, USP and ferrous fumarate tablets) and Femcon Fe (Norethindrone, Ethinyl estradiol tablets, ferrous fumarate tablets), respectively
Earlier review on this product Here.

Oxaliplatin (Eloxatin) injection: CAFC construed key patent’s claim broadly; decision favorable to innovator Sanofi

In a significant decision, The Court of Appeal for Federal circuit (CAFC) has rejected the claim construction of U.S. District Court for the District of New Jersey (decision by Judge J.A. Pisano) on key patent covering anti-cancer parenteral formulation of Oxaliplatin (Eloxatin). Earlier, the district court has granted summary judgment of non-infringement in favor of various generic players like Sandoz, Teva and Mayne Pharma (Hospira) on Oxaliplatin (Eloxatin) 50 mg/vial, 100 mg/vial, 200 mg/vial and 5 mg/ml injection.

Following patents are listed in Orange Book for Oxaliplatin (Eloxatin) 50 mg/vial, 100 mg/vial, 200 mg/vial and 5 mg/ml injection:

US5338874 (Expiry: Apr 07,2013): Which covers Optically pure cis-oxalato (trans- 1-1,2-cyclohexanediamine) Pt(II) wherein the melting point thereof is between 198C and 292 C

US5420319 (Expiry: Aug 08,2016): Which covers a Cis-oxalato(trans-1-1,2-cyclohexanediamine) Pt(II) complex having high optical purity represented by Formula 1 which possesses optical purity of 99.94% or more and a melting point between 198.3.degree. C. and 199.7.degree. C

US5716988 (Expiry: Aug 07,2015) : Which covers a pharmaceutically stable preparation of oxaliplatinum for the administration by the parenteral route, consisting of a solution of oxaliplatinum in water at a concentration of 1 to 5 mg/ml and having a pH of 4.5 to 6, the oxaliplatinum content in the preparation being at least 95% of the initial content and the solution remaining clear, colorless and free of precipitate after storage for a pharmaceutically acceptable duration of time.

US5290961 (Expiry Jan 12, 2013): Which covers a process of preparing a cis-platinum (II) complex of a 1,2-cyclohexanediamine isomer.

Sanofi-Aventis filed suit against Mayne Pharma (Hospira), Teva and Sandoz in June-July 2007 and their API supplier W.C. Heraeus GmbH in May 2008, for infringement of US5338874, which covers Oxaliplatin as product.

The District court's decision

The U.S. District Court for the District of New Jersey in it’s decision (on June, 2009) opined that although ‘874 patent covers optically pure oxaliplatin as product, however, the claim construction clearly suggests that claim in actual should be product by process claim. Also, court concluded that process limitation of ‘874 patent is separation of isomer using HPLC technique. Importantly, generic players are not using HPLC technique for resolution of isomer. Further, court upheld the validity of the patent but concluded no infringement of claim 1 by generic players Mayne Pharma (Hospira), Teva and Sandoz.

Court of Appeal for Federal Circuit (CAFC) decision
On june 30, 2009, Innovator Sanofi and Debiopharm appealed against the district court’s decision in CAFC, wherein they questioned claim construction by district court. Subsequently, on July 10, 2009 court stayed the district court’s Judgment.

Further, on Aug 7, 2009, USFDA approved ANDA of some generic players.

The CAFC was not in agreement with the claim construction of District court and opined that prior art Kidani process produced Oxaliplatin, which was 90% pure. Importantly, the ‘874 patent produced Oxalipaltin with pharmaceutical grade purity.

Further, District erroneously limited the disputed claim to process limitation by HPLC. The district court erred in construing composition claims as product by process claims. The patent specification and prosecution history focus on the property of the composition (optical purity) and not the process used to obtain the same. The specification defines the invention as Oxaliplatin of high optical purity and not the process used to obtain that purity.

The court vacated and remanded that summary judgment opinion back to U.S. District Court for the District of New Jersey

CAFC Opinion Here

Generic player affected by this ruling: Mayne Pharma (Hospira), Teva, Sandoz, W.C Heraeus, Barr, APP pharma and Abraxis Bioscience, Actavis, Fresenius Kabi, Sun Pharma, Ebewe Pharma, MN pharma (Par)

Dexmedetomidine hydrochloride (Precedex) 100 mcg base/ml: Innovator sued Sandoz

Innovator Orion and Hospira has sued generic player Sandoz in the U.S. to enforce their U.S. Patents covering the proprietary drug Dexmedetomidine hydrochloride (Precedex) 100 mcg base/ml (as reported by orion in press release Here )

Orion Corporation and Hospira, Inc. filed together a patent infringement lawsuit in the United States to enforce following Orange Book listed patents:

US4910214 (Expiry: Jul 15, 2013 ): Which covers the d enantiomer of medetomidine or a non-toxic pharmaceutically acceptable acid addition salt thereof. The said patent also covers, a pharmaceutical composition suitable for use in a method of sedation/analgesia or treatment of anxiety or hypertension comprising the d-enantiomer of medetomidine or a non-toxic pharmaceutically acceptable acid addition salt thereof in an amount sufficient to produce the desired effect in association with a pharmaceutical carrier

US6716867 (Expiry: Mar 31, 2019): Which covers a method of sedating a patient in an intensive care unit, which comprises administering to the patient an effective amount of dexmedetomidine of a pharmaceutically acceptable salt thereof, wherein the patient remains arousable and orientated.

Dexmedetomidine hydrochloride (Precedex) 100 mcg base/ml is approved for continuous intravenous sedation of initially intubated and mechanically ventilated patients in the intensive care setting for up to 24 hours and in non-intubated patients requiring sedation prior to and/or during surgical and other procedures.

Now, Sandoz's ANDA approval process would be delayed for 30 months as per Hatch-Waxman provisions.

Earlier news of IP Pharma Doc on this product Here

Bivalirudin (Angiomax) 250 mg/vial IV injection: Innovator confirmed receipt of Paragraph IV notice letter from Teva and Pliva

The innovator, M/S Medicines Company announced (in a press release Here) that it has received Paragraph IV Certification notice letters from generic players M/S Teva Parenteral and M/S Pliva wherein, generic players informed the Company that they have submitted Abbreviated New Drug Applications (ANDAs) to the U.S. Food and Drug Administration (USFDA) for approval to market generic versions of anti-clotting formulation Bivalirudin (Angiomax) 250 mg/vial IV injection.

The following patents are listed for this product:

US5196404 (Expiry: Sep 23, 2010): Which covers Bivalirudin as product

US7582727 (Expiry: Jan 27, 2029): Which covers pharmaceutical batches of a drug product comprising bivalirudin (SEQ ID NO: 1) and mannitol for use as an anticoagulant in a subject in need thereof, wherein the batches have a pH adjusted by sodium hydroxide, said pH is about 5-6 when reconstituted in an aqueous solution for injection, and wherein the batches have a maximum reconstitution time that does not exceed about 42 seconds and a maximum total impurity level that does not exceed about 2% as measured by HPLC.

The generic players have filed Para IV against ‘727 (Earlier, innovator announced grant of ‘727 patent Here). Probably, generic players have filed ANDA with Para III against ‘404 patent.

Earlier, innovator got final approval to market Bivalirudin (Angiomax) 250 mg/vial IV injection from USFDA on Dec 15, 2000.

Tramadol hydrochloride 100 mg, 200 mg and 300 mg ER tablets (Ultram ER): Innovator appealed against patent invalidation decision

Innovator Purdue and Napp Pharma has filed an appeal with the U.S. Court of Appeals for the Federal Circuit (CAFC), challenging the United States District Court for the District of Delaware opinion of invalidation of two key patents US6254887 and US7074430, which covers Tramadol hydrochloride 100mg and 200mg ER tablets (Ultram ER).

Earlier on August 16, 2009, United States District Court for the District of Delaware, Honorable Judge Kent A. Jordan has issued an opinion in favor of generic player Par Pharmaceuticals in the patent-infringement litigation relating to Tramadol hydrochloride 100 mg and 200 mg ER tablets (Ultram ER).

The court opined that disputed claims 3, 13, 27 and 29 of US6254887 patent and claims 5, 7 and11 of US7074430 patents are infringed by Par’s generic product. However, the disputed claims are invalid and obvious in the light of Oshlak (US5580578) disclosure (alone) and Oshlak in combination with Kaiko (US5478577), Lintz and Stewart Leslie (one of the co-inventor of disputed patents) article entitled “Continues controlled release formulations”.

Earlier news of IP Pharma Doc on this product Here

Salmon Calcitonin 200 IU/SPRAY (Fortical): Court issued permanent injunction against Apotex

In a patent dispute between generic player Apotex and innovator Upsher-Smith Lab, the U.S. District Court for the Southern District of New York has issued permanent injunction against generic player. (as reported by innovator in press release Here )

The court has opined that the disputed patent US6440329, which was reissued after corrections by USPTO as USRE40812 is valid.

Earlier in July, 2006, Apotex filed ANDA with Para IV certification against ‘329 patent. The innovator asserted claim 19 of he ‘329 patent against Apotex. Importantly, the claim 19 was reissued as such in the reissued patent by USPTO.

USRE40812 (Assignee: Unigene Laboratories, Reissued date:June, 2009 Expiry: Feb 2, 2021): The disputed claim 19 covers a liquid pharmaceutical composition comprising about 2,200 MIC units of salmon calcitonin, about 20 mM citric acid, about 0.2% phenylethyl alcohol, about 0.5% benzyl alcohol, and about 0.1% polyoxyethylene(20) sorbitan monooleate.

The essential feature of claim 19 is the use of citric acid in Salmon Calcitonin, which enhanced shelf stability and bioaviailability of the formulation.

The Apotex challenged the said patent based on obviousness grounds. Further, Apotex asserted that the claimed formulation in RE’812 is substantially similar to M/S Novartis Pharma’s marketed formulation Miacalcin (the formulation comprises of 2200 IU/ ml 0f Salmon Calcitonin, sodium chloride as tonicity agent, nitrogen as sparging, Benzalkonium chloride as absorbtion enhancer agent, preservative and surfactant, HCl as PH adjusting agent), which was approved by USFDA on Aug 17, 1995.

Arguably, Apotex alleged that it would have been obvious for person having ordinary skilled in the art (PHOSITA) to replace Benzalkonium chloride in Miacalcin formulation by citric acid as absorption enhancing agent to devolp Fortical formulation.

Importnatly, in the prior art, there was no reference, which could suggest that Citric acid can act as absorption enhancing agent. Further, the court observed that a PHOSITA would have not motivated to select Citric acid as absorption enhancing agent.

Also, court observed that use of 0.1% polyoxyethylene(20) sorbitan monooleate and benzyl alcohal in a single nasal spray formulation is not obvious. Further, prior art teaches away from the said combination.

In the light of above evidences, court opined that the claimed invention is not obvious and denied Apotex’s summary judgment request and granted innovator’s summary judgment request and issued permanent injunction against generic player.

Innovator UPSHER SMITH got final approval from USFDA to market Salmon Calcitonin 200 IU/SPRAY (Fortical) on Aug 12, 2005

Acetaminophen 325 mg + Tramadol Hydrochloride 35.5 mg tablets (Ultacet): The CAFC opinion quite favorable to innovator

The Court of appeal for Federal circuit (CAFC) has reversed a portion of a previously decided summary judgment on patent litigation between innovator Ortho-McNeil ( a subsidiary of Johnson & Johnson) and Caraco (subsidiary of Sun Pharma), Teva regarding Acetaminophen 325 mg + Tramadol Hydrochloride 35.5 mg tablets (Ultracet). Further, the court has remanded the litigation to a lower court for further proceedings.

Background of the case

Prior Art: 1) Kurt Flick et al patent US3652589 published in 1972, which disclosed Tramadol and it’s combination with other analgesics. The example 23 of Flick’s patent disclosed combination of Tramadol with Acetaminophen and two other drugs.

2) Also, a German publication “WHO cancer pain guidelines” suggested various combinations of analgesics for treatment of Cancer pain.

United States district court for the district of New Jersey’s decision

Innovator Ortho claimed the combination of Tramadol + Acetaminophen in US5336691. The patentability basis as per '691 was synergistic action of both analgesics. The Tramadol is centrally acting analgesics, whereas, Acetaminophen acts by inhibiting cyclooxygenase (COX) enzyme.

Innovator got final approval to market this product on Aug 15, 2001. Afterwards due to commercial success of Ultracet, some generic players like Barr and Kali labs filed ANDA with invalidation grounds against said patent.

The example 23 of Flick’s patent has disclosed ratio of 1:10 of Tramadol + Acetaminophen. The said ratio was being covered under the scope of Ortho’s patent. Also, a German publication “WHO cancer pain guidelines” suggested various combinations of analgesics during treatment of Cancer.

Innovator in a bid to protect the patent from invalidation, filed re-examination and reissue request with USPTO to amend the disputed claims. The innovator disclosed all the references cited against the patent by generic players to examiner. Also, innovator redrafted the claims to overcome obviousness challenge of generic players. Finally, examiner reissued the US5336691 as USRE39221 after some changes.
The said reissued patent (which is listed in orange book for Ultarcet) covers:

USRE39221 (Expiry: Aug 9, 2011): The reissued claims covered a pharmaceutical composition comprising a Tramadol material and Acetaminophen, wherein the ratio of the tramadol material to acetaminophen is about 1:5.

After reissue of ‘691 as RE’221, the innovator asserted claims of ‘221 against generic players like Barr and Kali Labs. The generic players in turn filed for Summary Judgment motion of invalidity and non-infringement.

On Aug 12, 2008, the United States district court for the district of New Jersey’s Judge D.M Cavanaugh issued a summary judgment opinion and invalidated the asserted claims 43-48, 51, 54, 67, 69, 72 and 74 of ‘221 patent as obvious in the light of prior art. Also, the court invalidated the claim 6 of ‘221 patent based on prior art and found the claim to be anticipated and obvious.

Court of appeal for Federal circuit Decision
The innovator Ortho appealed against the said decision in CAFC on Aug 25, 2008.

The court observed that claims 6, 43-48, 51, 54, 67, 69, 72 and 74 covers combination of Tramadol + Acetaminophen from about 1:5 to about 1:19. A single tablet containing these two important ingredients was not disclosed in prior art.

Further, during trial, court gave importance to innovator’s expert testimony. The expert opined that Filck’s reference couldn’t obviate the said combination. Also, the interaction between Tramadol and Acetaminophen was poorly understood in 1990. The expert further opined that Flick’s broad statement that Tramadol “often” displayed synergistic action in combination with other analgesics would not be enough to obviate Tramadol + Acetaminophen ratio of about 1:5 to about 1:19. Also, expert testified that German reference teaches away from selecting the claimed combination.

Finally, the court in a 2-1 decision (panel of Judges Mayer, Prost and Moore), has remanded the litigation to United States district court for the district of New Jersey for further proceedings. The court opined that the claims 43-48, 51, 54, 67, 69, 72 and 74 of ‘221 patent are not invalid due to obviousness. Also, court has opined that claim 6 of the disputed patent is invalid due to obviousness (and not due to anticipation).

Also, the fellow Judge H.R Mayer has written dissent against said decision. As per Judge Mayer, the ‘221 patent is not novel as the said patent covers combination of two well known analgesics Tramadol and Acetaminophen”

Opinion of CAFC Here

The generic players
Following generic players have final approval for this product:

1) Barr (ANDA approved on Jul 26, 2006)

2) Caraco (ANDA approved on Dec 16, 2005)

3) Kali Labs (ANDA approved on Apr 21, 2005)

4) Mylan (ANDA approved on Sep 26, 2008)

Earlier, Innovator has settled with generic player Kali Labs (a subsidiary of Par Pharma) in July, 2007. The Kali labs have licensing agreement with innovator.

The revival of this case will certainly help innovator in blocking other generic players

Paragraph IV certification reported by USFDA (August 25, 2009)

1. Amlodipine Besylate and Atorvastatin Calcium 5 mg + 80 mg tablets (Caduet) Paragraph IV filed on April 4, 2009

2. Fluvoxamine Maleate Extended- release Capsules (Luvox CR) Paragraph IV filed for 100 mg strength on May 18, 2009 and for 150 mg strength on April 13, 2009

3. Minoxidil 5% Topical Aerosol Foam (Men’s Rogaine) Paragraph IV filed on April 6, 2009

4. Paroxetine Hydrochloride 37.5 mg Extended-release Tablets (Paxil CR) Paragraph IV filed May 19, 2009

5. Testosterone 1% Gel Metered-dose Pump (Androgel) Paragraph IV filed on December 19, 2008

(Source: USFDA website)

Montelukast (Singulair) 10 mg tablets: Court sided with innovator; generic version delayed till patent expiry (2012)

Generic pharma giant Teva Pharma (announced in a press release Here ) that the U.S. District Court for the District of New Jersey has issued a decision in its litigation over the Company's Abbreviated New Drug Application (ANDA) to market its generic version of Merck's Singulair® (Montelukast Sodium) Tablets, holding that product patent listed in Orange Bokk is valid and enforceable. Teva is currently reviewing the Court's decision to determine its next course of action.

Earlier in a major victory for Innovator Merck, U.S. District Court for the District of New Jersey opined that Teva’s generic product would infringe plaintiff’s valid patent. The Judge ordered Teva not to make generic Singulair, and ordered the U.S. Food and Drug Administration not to approve the generic Singulair until after Merck's patent expires in 2012.

Innovator has listed following disputed patent in Orange Book for Montelukast’s (Singulair) 10 mg tablets and 4 mg granules:

US5565473 (Expiry: Aug 3, 2012): which covers unsaturated hydroxyalkylquinoline acids as leukotriene antagonists, including Montelukast as product.The said patent is a blocking patent for other generic players and is a barrier to generic entry.

Earlier, independent firm Article One Partners LLC announced that its online community found two pieces of evidence that suggest the asthma and allergy drug's key ingredient isn't novel. Law firm has alleged that innovator during prosecution of ‘473 patent has not disclosed some articles authored by Merck's scientist Dr. Robert Young (who proposed a receptor model on anti-allergic effects). Further, law firm alleged that the said article were very important for patentability determination of ‘473 patent. The same grounds were the basis for validity attack by generic player Teva. However, court was not convinced with the invalidation grounds.

Teva is first para IV filer for Montelukast tablets 10 mg/tablet. Teva filed its ANDA with para IV certification on December, 2006. Further, in May, 2009 Teva got tentative approval from USFDA for Montelukast 10 mg Tablets (Singulair) .

In March 2009, a firm that specializes in challenging the validity of patents has requested the USPTO to re-examine innovator Merck’s Orange Book listed patent US5565473 for Montelukast Tablets (Singulair). The said patent is under re-examination by USPTO.

Earlier news of IP Pharma Doc on this product Here

Gemcitabine HCl for injection (Gemzar) 200mg base/vial and 1 g base/vial: District court invalidated method of use patent

Innovator Eli Lilly announced (in a press release Here ) that the U.S. District Court for the Eastern District of Michigan has granted a motion by Sun Pharmaceuticals for partial summary judgment against key patent covering method of use of Gemcitabine HCl for injection (Gemzar) 200mg base/vial and 1 g base/vial.

The following patents are listed in Orange Book for this product:

US4808614 (Patent Expiry: Nov 15, 2010): Which covers various nucleosides like Gemcitabine as product

US5464826 (Patent Expiry: May 7, 2013): Which covers a method of treating susceptible neoplasms in mammals comprising administering to a mammal in need of such treatment a therapeutically effective amount of Gemcitabine.

U.S. District Court for the Eastern District of Michigan has invalidated innovator Eli Lilly's method of use patent '826 patent. The court invalidated the said patent on the basis of obviousness type of double patenting. Innovator's coumpound patent '614 discloses use of Gemcitabine for the treatment of viral infection. Also, the said patent has disclosed use of Gemciatabine as anticancer drug. Later on, innovator got '826 patent, wherein, innovator claimed method of use of Gemcitabine for the traetment of cancer. Importantly, Sun pharma identified this important point and challenged '826 patent on double patenting grounds in the light of '614 disclosure. The court construed the claims of earlier and later patents and determined their diffrence. Finally, the court opined that claim 12 of '614 covers anticancer use of Gemcitabine and the claim 2, 6 and 7 of '826 patents have reclaimed the same use, accordingly, claims are not patentably distinct.

As per press release, innovator opined that Gemcitabine HCl for injection (Gemzar) compound patent (‘614) would remains in place until November 15, 2010, accordingly, no generic version of the drug will enter the U.S. marketplace until then.

"We strongly disagree with the Court's ruling granting summary judgment in favor of the generic challenger," said Robert A. Armitage, senior vice president and general counsel for Lilly. "We continue to believe that our Gemzar method-of-use patent is valid and will be upheld by the courts. We intend to pursue an appeal of this decision with the Court of Appeals for the Federal Circuit.