Wednesday 30 September 2009

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

Tuesday 29 September 2009

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/

Friday 25 September 2009

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.

Wednesday 16 September 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 )

Tuesday 15 September 2009

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.

Friday 11 September 2009

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)

Monday 7 September 2009

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.

Friday 4 September 2009

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

Wednesday 2 September 2009

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

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