Ropinirole Hydrochloride (Ran-Ropinirole) 0.25 mg, 1.0 mg, 2.0 mg, and 5.0 mg tablets: Ranbaxy got “Notice of Compliance” to market in Canada

Indian pharma giant Ranbaxy Pharmaceuticals Canada Inc announced that RLL has received approval in Canada to manufacture and market Ran-Ropinirole 0.25 mg, 1.0 mg, 2.0 mg, and 5.0 mg tablets (Ropinirole Hydrochloride) from Health Canada, Therapeutic Products Directorate (TPD). Total generic market size of Ropinirole Hydrochloride tablets in Canada is $4.8 million ($CAD) [IMS-CDH: July 2008]. Ran-Ropinirole tablets are indicated for use as an anti-parkinsonian agent and dopamine agonist.

Malathion 0.5% topical Lotion (Ovider): Innovator Taro Sued generic players in a bid to block generic version

Innovator Taro Pharmaceutical Industries (announced in a press release Here ) that it has filed a patent infringement lawsuit against generic players Synerx Pharma, DPT Labs and Karalex Pharma in the United States District Court for New Jersey for infringement of following Orange Book listed patent:

US7560445 (Assignee: Taro Pharma; Expiry: Feb 1, 2027): The patent covers a topical pharmaceutical composition comprising malathion, said malathion having a purity of greater than about 98.5%

Malathion 0.5% topical Lotion (Ovider) is used for the treatment of patients infected with pediculus humanus capitis (head lice and their ova) of the scalp hair

Norgestimate+Ethinyl Estradiol (Ortho Tri-Cyclen) Tablets: Teva And Ortho-McNeil-Janssen Settled patent litigation; generic version delayed till 2015

Generic player Teva Pharma announced (in a press release Here ) that Teva has entered into a licensing agreement with innovator Ortho-McNeil-Janssen to settle the patent infringement lawsuit in the U.S. District Court for the District of New Jersey related to Teva's generic version of the oral contraceptive formulation Norgestimate+Ethinyl Estradiol (Ortho Tri-Cyclen) 0.18 + 0.025 mg, 0.215 +0.025 mg and 0.25 + 0.025 mg Tablets

Under the terms of the settlement, Teva will obtain a release for past sales of its generic product, in exchange for an undisclosed royalty payment. Teva also will obtain a license to re-enter the market on December 31, 2015, or earlier in certain circumstances.

The settlement will not become effective until the court enters a proposed consent judgment upholding the validity and enforceability of Ortho's patent.

Background

The generic player Barr (Now, a subsidiary of Teva Pharma) has earlier challenged innovator’s Orange Book listed key patent for Norgestimate+Ethinyl Estradiol (Ortho Tri-Cyclen) 0.18 + 0.025 mg, 0.215 +0.025 mg and 0.25 + 0.025 mg Tablets in October, 2003, accordingly, innovator sued Barr in New Jersey District Court for the infringement of following Orange Book listed patent:

US6214815 (Assignee: Ortho-McNeil Pharmaceuticals; Date of grant: April 10, 2001; Expiry: Dec 9, 2019): The independent claims 1 and 4 were at issue in this trial, the disputed claims covers:

1. A method of contraception which comprises administering for 21 successive days to a female of childbearing age a combination of 17.alpha.-ethinylestradiol and norgestimate for the first 7 days in a daily dosage corresponding to 25 .mu.g of 17.alpha.-ethinylestradiol and 0.180 mg of norgestimate, for the succeeding 7 days a daily dosage equal to 25 .mu.g of 17.alpha.-ethinylestradiol aid 0.215 mg of norgestimate; and for the next 7 days a daily dosage equal to 25 .mu.g of 17.alpha.-ethinylestradiol and 0.250 mg of norgestimate; followed by 7 days without estrogen and progestogen administration.

4. A triphasic oral contraceptive unit having 21 separate dosage units, adapted for successive daily oral administration comprising: 7 dosage units containing in admixture with a pharmaceutically acceptable carrier, 25 .mu.g of 17.alpha.-ethinylestradiol and 0.180 mg of norgestimate, 7 dosage units containing in admixture with a pharmaceutically acceptable carrier, 25 .mu.g of 17.alpha.-ethinylestradiol and 0.215 mg of norgestimate; and 7 dosage units containing in admixture with a pharmaceutically acceptable carrier, 25 .mu.g of 17.alpha.-ethinylestradiol and 0.250 mg of norgestimate; and optionally containing 7 additional dosage units free of estrogen and progestogen.

Generic player Barr challenged ‘815 patent on obviousness and anticipation grounds, based on prior art disclosure in US4616006 and US4628051. Also, some of the terms used in claim language like “method of contraception” and “oral contraceptive unit” were contentious issue, for which Marksman hearing held in 2005. Further, as per Marksman hearing held in 2005, court construed the claim language based on intrinsic evidences. In Oct 2006, court denied summary judgment to both parties.

On July 1, 2009, Teva who announced "at risk" launch (in press release here) agreed to suspend generic launch till preliminary Injunction opinion (as per Teva press release Here and Here). The PI proceedings were ongoing when both the parties announced settlement.

Probably, patent litigation settlement is beneficial to both the parties. Innovator for the time being is able to delay generic challenge till 2015. For Teva, they will have certainty in product launch without the threat of litigation (they were in litigation with innovator for the last 6 years). For American public, they will get cheaper generic version from 2015 onwards (or earlier), otherwise, they would have to wait till 2019.

Earlier, innovator got approval to market this product on Aug 22, 2002.

Also, as per complaints filed by innovator in New Jersey District Court, innovator has sued generic players like Sandoz and Watson for this product.

Generic Pharma Press Releases

Rivastigmine 1.5, 3, 4.5 and 6 mg capsules & 2 mg/ml solution: Generic player Synthon announced (in a press release Here ) that Synthon has successfully completed multiple decentralized procedures (DCP) for Rivastigmine. Regulatory clearance has been obtained for Synthon's product in nearly all European countries. Registration has been obtained for multiple dosage forms including capsules (1.5, 3, 4.5 and 6 mg) and an oral solution (2 mg/ml). Synthon' s Rivastigmine capsules and oral solution are a fully generic and bioequivalent version of the brand product Exelon®.

Ranbaxy’s manufacturing facility got cGMP compliance nod from MHLW- JAPAN Indian Pharma giant Ranbaxy Laboratories Limited (Ranbaxy) announced (in a press release Here ) that the Ministry of Health and Labour Welfare (MHLW-Japan), have issued a Good Manufacturing Practice (GMP) certificate for its non-sterile manufacturing site located at Dewas (India).

Ran-Simvastatin (Simvastatin) 5 mg, 10 mg, 20 mg, 40 mg and 80 mg tablets: Indian Pharma giant Ranbaxy Pharmaceuticals Canada Inc. (RPCI) has received approval in Canada to manufacture and market Ran-Simvastatin 5 mg, 10 mg, 20 mg, 40 mg and 80 mg tablets (Simvastatin) from Health Canada, Therapeutic Products Directorate (TPD). (Press release from Ranbaxy Here )

Haloperidol Tablets USP, 10 mg and 20 mg: The USFDA approval to Mylan ANDA for Haloperidol Tablets USP, 10 mg and 20 mg (as reported by Mylan in press release Here)

Trospium chloride Extended Release 60 mg Capsules (Sanctura XR): Innovator Allergan sued Watson in a bid to block generic version

Generic player Watson Pharma confirmed (in a press release Here) that company has filed an Abbreviated New Drug Application (ANDA) with Paragraph IV certification against innovator Supernus Pharma and Allergen’s Orange Book listed patents on Trospium chloride Extended Release 60 mg Capsules (Sanctura XR). Watson has challenged following Orange Book listed patent:

US7410978 (Assignee: Supernus; Date of grant: August 12, 2008; Expiry: Feb 1, 2025): The patent covers a pharmaceutical composition suitable for a once-a-day administration of trospium chloride comprising controlled release solid, trospium chloride-bearing particulates, at least a portion of which releases trospium chloride in the lower gastrointestinal (GI) tract, such that once-a-day administration of said pharmaceutical composition provides steady state blood levels of trospium that are comparable to steady state blood levels of trospium achieved with twice daily administration of 20 mg immediate release trospium chloride tablets, said particulates comprising at least one polymer selected from enteric polymers, release controlling polymers, or combinations thereof.

Trospium chloride Extended Release 60 mg Capsules (Sanctura XR) is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and urinary frequency.

Further, innovator Allergan filed patent infringement suit against Watson on July 13, 2009 in the U.S. District Court for the District of Delaware.

Earlier, innovator Allergan got approval to market this product on Aug 3, 2007.

As per press release, Watson believes it may be first to file an ANDA for generic trospium extended-release capsules.

For the twelve-months ended March 31, 2009, Trospium chloride Extended Release 60 mg Capsules (Sanctura XR) had total U.S. sales of approximately $42 million, as per IMS Health data.

Escitalopram Oxalate (Lexapro) 5, 10, and 20 mg Tablets: Sun Pharma (Caraco) and Forest settled patent litigation

Innovator Forest Labs and H. Lundbeck have settled pending litigation with generic player Sun pharma and its subsidiary Caraco on Orange Book listed patents USRE34712, US6916,941, and US7420,069 (As per Forest’s press release Here and Sun Pharma's press release Here) on Escitalopram Oxalate (Lexapro) 5, 10, and 20 mg tablets .

Before settlement, the companies were litigating on USRE34712 (innovator sued Caraco on patent covering substantially pure Escitalopram in July, 2006), US6916941 (Caraco filed Declaratory Judgment action of patent non-infringement against patent covering particle size of Escitalopram in Feb, 2007), and US7420069 (Caraco filed Declaratory Judgment action of patent non-infringement against patent covering median particle size of 40-200 micrometer size of Escitalopram in Jan, 2009)

As per Caraco's press release Here, Forest has agreed to provide licenses to Caraco for any patents related to Escitalopram Oxalate (Lexapro) 5, 10, and 20 mg tablets with respect to the marketing of Caraco's generic version of the product as of the date that any third party generic enters the market with final approval from the USFDA other than an authorized generic or the first filer with Hatch-Waxman related exclusivity. Also, Forest will reimburse Caraco for a portion of its attorney's fees related to this litigation. Additionally, Sun Pharma will license some patents to innovator pertaining to Escitalopram.

Background
In May 2006, generic player Caraco filed ANDA with para IV certification against ‘712 and ‘941 patent listed for Escitalopram Oxalate (Lexapro) 5, 10, and 20mg tablets. Subsequently, innovator sued Caraco for the infringement of ‘712 patent in Eastern district of Michigan, however, innovator did not sue Caraco on ’941 patents. Importantly, a court decision on ‘941 patent was essential for Caraco to trigger first generic player Ivax’s (Teva) 180 days exclusivity.

Caraco then filed a complaint seeking a declaratory judgment that its generic version of Lexapro does not infringe the '941 patent. Forest granted Caraco a ‘covenant not to sue’ for infringement of the '941 patent. Due to the ‘covenant not to sue’, the district court dismissed Caraco's complaint for lack of jurisdiction.

Later on, Caraco appealed against District court’s decision in the US Court of appeal for Federal Circuit (CAFC), which opined that an ANDA applicant's declaratory judgment action for non-infringement meets Article III's "case or controversy" requirement. The Federal Circuit further determined that the issues are relevant and the case is not moot. Further, the court held that Caraco's action presents an ongoing Article III case and controversy, reversed the district court's decision dismissing the case, and remanded the case for a decision on the merits.

The patent litigation of Caraco on this product paved the way for other generic players on declaratory Judgment provisions, wherein, subsequent generic players could establish the certainty in generic launch by initiating the first generic filer's 180 days exclusivity through DJ action.

Amlodipine besylate (Norvsac) 2.5 mg, 5 mg and 10 mg tablet: Ratiopharm Canada wins important patent legal battle with Pfizer

Generic player Ratiopharm Canada has won a five-year long legal battle against innovator Pfizer’s key patent covering Amlodipine besylate (Norvsac). The said decision will allow the marketing of Amlodipine Besylate (Norvasc) 2.5 mg, 5 mg and 10 mg tablets by generic manufacturers.

Generic player Ratiopharm challenged the following patent in 2004 :

CA1321393 (Expiry: August, 2010): which covers A process for preparing the besylate salt ofamlodipine characterised by the steps of reactingamlodipine base with a solution of benzenesulphonic acid or its ammonium salt in an inert solvent and recoveringthe besylate salt of amlodipine.

As per the Federal Court's decision announced on July 8, 2009 by Honorable Judge Roger Hughes, the disputed patent was declared invalid.

Ratiopharm was the first company to challenge the Amlodipine Besylate patent in 2004 and got favorable decision from Federal Court in February, 2006. Later on, Pfizer appealed the decision in the ratiopharm case and won the appeal.

Pfizer will appeal against said decision as reported by fiercebiotech Here

Link to Bloomberg news Here

Ortho Tri-Cyclen (Norgestimate+Ethinyl Estradiol): Teva stopped shipping the generic version till Preliminary Injunction decision

Teva Pharma (as per press release Here) has stopped shipping a generic version of innovator Johnson & Johnson's birth control pill Ortho Tri-Cyclen (Norgestimate / Ethinyl Estradiol).

Teva agreed to stop shipping the drug till a preliminary injunction hearing in a patent infringement lawsuit from innovator Johnson & Johnson.

The Preliminary Injunction hearing is scheduled to begin on July 15.

Earlier on July 1, 2009, Teva announced (announced in a press release Here) the generic approval and launch of Ortho Tri-Cyclen.

Pioglitazone Hydrochloride (Actos) 15, 30 and 45 mg tablets: Innovator Takeda sued generic player

Innovator Takeda Pharma has sued Indian generic player Torrent Pharma in U.S. District Court for the Southern District of New York in a bid to block generic challenge on Pioglitazone Hydrochloride (Actos) 15, 30 and 45 mg tablets. Innovator Takeds in it’s complaint has asserted six patents against Torrent and has requested court to block generic approval till (June, 2016) expiry of asserted patents.

Earlier, innovator Takeda has successfully defended the invalidation bid of generic players against it’s key patent (product patent) US4687777 (Expiry: JAN 17,2011) by generic players Alphapharm and Mylan as reported by us Here and Here

Innovator Takeda got approval to market this product from USFDA on Jul 15, 1999.

For complete story please check article published in Bloomberg Here

Donepezil (Aricept) 5 and 10 mg tablets: Apotex filed DJ request in a bid for generic approval

Reuters has reported Here that Generic player Apotex in a bid to trigger 180 days exclusivity of generic player Ranbaxy has filed Declaratory Judgment request of non-infringement against innovator Esai’s Orange Book listed patents on Donepezil Hydrochloride (Aricept) 5 and 10 mg tablets in the U.S. District Court for the Middle District of North Carolina

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

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

Apotex has filed ANDA with para III certification against ‘841 product patent and Para IV against rest of the patents.

The first ANDA was filed for this product around early 2003 by generic player Ranbaxy, accordingly, it’s a pre-medicare, prescription drug improvement, and modernization act of (MMA) case, wherein, generic company were eligible as First Para IV filer by filing patent specific para IV filing. Probably, Ranbaxy filed para III against Product patent and para IV against rest of the patents and innovator choose not to initiate litigation against Ranbaxy.

Now, to trigger 180 days clock of First para IV filer, following is desirable:
1) A court decision of patent invalidity or non-infringement by subsequent generic players
2) By any one of the first to file generic enter into the market

In case of ANDA filed prior to MMA act, a bottleneck can occur when the first para IV filer does not enter the market and innovator refuses to sue subsequent generic player, thereby preventing the finding of invalidity or non-infringement.

Ranbaxy and Teva are first para IV filer for this product. Teva, who has litigated with the innovator on invalidation of product patent ‘841 has got adverse decision from court on preliminary injunction decision as reported by us Here .

As per complaint, Apotex argues that due to Ranbaxy’s cGMP problems, Ranbaxy would not be able to get final FDA approval and launch the product after patent expiry, accordingly, a DJ action is necessary to remove the hurdles for subsequent ANDA filers.

Also, as per complaint, Apotex has highlighted the fact that USFDA has erroneous identified generic giant Teva as the first para IV filer.

Furthermore, the generic player Apotex has filed Citizen petition with USFDA on July, 2009 against First Para IV filer status of Teva for this product.

Donepezil (2-[(1-benzyl-4-piperidyl)methyl]- 5,6-dimethoxy-2,3-dihydroinden-1-one), marketed under the trade name Aricept (Eisai), is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. The USFDA first approved Aricept tablets in 1996. The drug is Tokyo-based Eisai's biggest product, with $2.16 billion in worldwide sales in the year ended in March 2007.

DOXYCYCLINE DELAYED RELEASE (ORACEA ) Capsules 40MG: Innovator sued Lupin in a bid to block generic varsion

Innovator GALDERMA LABS LP has sued Indian generic player Lupin in US District Court for the District of Delaware for filing ANDA with Para IV certification on DOXYCYCLINE DELAYED RELEASE (ORACEA ) Capsules 40 mg.

Following patents are listed in Orange Book for this product:

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.

As per complaint, innovator has asserted all four patents against generic giant Lupin. Generic player Lupin is an aggressive generic player with many paragraph IV ANDA filings (including First to file para IV filings) in USA.

Earlier in March 2009, innovator has sued another generic player Mylan for filing ANDA with Para IV certification against Orange Book listed patents for DOXYCYCLINE DELAYED RELEASE (ORACEA ) Capsules 40 mg .

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

DOXYCYCLINE DELAYED RELEASE (ORACEA ) Capsules 40 mg is indicated for the treatment of inflammatory lesions (papules and pustules) of rosacea in adult patients.

Bicalutamide (Casodex) 50 mg tablets: Generic approvals

Various generic players have received final approval to market anti-cancer formulation Bicalutamide (Casodex) 50 mg tablets after the expiry of product patent US4636505 (Expiry: Apr 1, 2009) in USA.

Following generic players have got final approval from USFDA:

1. Teva

2. Synthon
3. Kudoco Ireland
4. Sandoz
5. Accord Healthcare
6. Zydus Pharma
7. Sun Pharma
8. Mylan

The generic Bicalutamide (Casodex) 50 mg tablets are bioequivalent to Casodex® tablets from AstraZeneca. As per IMS, Casodex® tablets have annual sales of approximately USD 314 million in the US.

Earlier, innovator has got approval from USFDA to market this product on October 4, 1995.

Bicalutamide (Casodex) 50 mg tablets are an androgen receptor inhibitor for the treatment of Stage D2 metastatic carcinoma of the prostate.

Imatinib Mesylate tablets (Gleevac): IP Appellate Board refused patent to innovator Novartis in India

In a significant and pro-patient judgment, the Intellectual Property Appellate Board (IPAB), has ruled that innovator Novartis's controversial anti-cancer drug, Imatinib Mesylate tablets (Gleevac), lacks patentability and refused patent to innovator.

The said patent was challenged by Indian generic players like Natco, Ranbaxy, Cipla and some NGO’s like Cancer Patient Aid Association.The IPAB panel of Z.S Negi (chairman) and PC Chakraborty (Technical Member) opined that the beta crystalline version of Imatinib Mesylate was not patentable under Section 3(d) of the Indian Patent Act and the molecule do not have enhanced efficacy in comparison to earlier known pharmaceutical derivatives.

Imatinib was first discovered as free base and innovator filed patent application in regulated market (US & Europe) around 1993. Later on, innovator improved various physical and chemical fetures of Imatinib by preparing as mesylate salt. Further during pre-formulation studies, innovator obtained thermodynamically stable and lesser hygroscopic crystalline form Beta of Imatinib Mesylate. The patent application on crystalline form Beta of Imatinib Mesylate was opposed in India. The marketed Imatinib Mesylate tablets (Gleevac) contains crystalline form Beta.

Earlier, innovator Novartis filed patent application in 1999 on crystalline form Beta of Imatinib Mesylate, subsequently; Chennai patent office rejected the patent application under section 3(d) of Indian patent act. Novartis appealed against this decision to IPAB. Also, Novartis unsuccessfully challenged Indian patent section 3(d).

As per section 3(d) of Indian patent act, incremental inventions of known substances like the pharmaceutical acceptable salts, esters, polymorphs, metabolites, particle size, complexes, co-crystals, combinations are unpatentable unless they differ significantly in terms of therapeutic efficacy.


The IPAB also acknowledged the fact that innovator has successfully patented similar invention in about 35-40 other countries, however, for country like India the treatment would cost around 1.2 lac per month, which is quite high for poor patients.

Also, board opined that claims in the patent are novel and non-obvious to person having ordinary skilled in the art, however, the invention has not significantly enhanced therapeutic activity to overcome patent application rejection under Indian patent act’s section 3(d).

Valacyclovir Hydrochloride (Valtrex) 500 mg and 1 g tablets: Dr. Reddy's got tentative approval

Hyderabad based generic player Dr. Reddy's Laboratories has received tentative approval on June 26, 2009 from the USFDA on generic Valacyclovir hydrochloride (Valtrex) 500 mg and 1 g tablets. The product patent US4957924 will expire on Dec 23, 2009. Also, innovator has listed two additional patents in Orange Book for this product US5879706 and US6107302 (both patents will expire on Jul 19, 2016), which cover polymorph and formulation of Valacyclovir.

The generic player Ranbaxy have got final approval for this product on January 31, 2007, however, as per licensing agreement with innovator Glaxosmithkline (GSK), Ranbaxy will enter into the market in later half of 2009. Importantly, Ranbaxy is first Para IV filer for this product.

The other generic players who have received tentative approval from USFDA for this product are Sandoz (July 30, 2007), Teva (October 4, 2007), Mylan (January 30, 2007), Watson (January 18, 2007). The other generic players may launch their product after the expiry of 180 days exclusivity of Ranbaxy.

Valacyclovir tablets 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, suppression of genital herpes in immunocopetent and HIV-infected individuals, reduction of risk of heterosexual transmission of genital herpes

Generic update

The generic player Apotex has filed a complaint in the U.S. District Court for the Middle District of North Carolina for declaratory judgment of non-infringement for Valacyclovir Tablets.

As per complaint, Apotex argues that due to Ranbaxy’s cGMP problems, a DJ action is necessary to remove the hurdles for subsequent ANDA filers. Ranbaxy is first para IV filer for this product. Apotex's action is aimed at triggering the 180 days exclusivity of Ranbaxy.

Pharma press release

1. Ursodiol tablets 250 mg and 500 mg: Authorized generic leader Prasco Laboratories announced that it has entered into a distribution and supply agreement with Axcan Pharma. for Authorized Generic versions of Ursodiol 250 mg and 500 mg tablets. The details are Here

2. Azelastine (Optivar) ophthalmic solution: Indian Pharma giant Sun Pharma announced in a press release Here the tentative approval of ophthalmic antihistamine formulation Azelastine (Optivar) ophthalmic solution 0.05%.

Levofloxacin (levaquin) tablets: Court upheld validity of SPC and patent

In a significant decision by THE HONOURABLE MR JUSTICE KITCHIN of Court of Appeal for England and Wales on dispute between generic player Generics (UK) Ltd v Daiichi Pharma (innovator), court opined that SPC (supplementary protection certificate no. SPC/GB97/085) granted to product patent European Patent (UK) No. 0206283, which covers Levofloxacine is justified and not invalid. The ‘283 patent relates to the S (-) enantiomer of a racemic compound called ofloxacin. Ofloxacin is a member of the quinolone class of anti-microbial agents. The R (-) enantiomer of ofloxacin is known as Levofloxacin. The application for the Patent was filed on 20 June 1986 and it proceeded to grant on 27 January 1993. On 6 June 1997, UK marketing authorisations were granted in respect of Levofloxacin, subsequently, the SPC was duly granted to ‘283 patent on 13 July 1998. The Patent expired on 20 June 2006, but the SPC will expire on 19 June 2011.

The generic player Generics UK challenged the SPC of this patent First, it is said that the SPC is invalid pursuant to Article 15 of Council Regulation (EEC) No 1768/92 ("the SPC Regulation") because grounds exist which would have justified revocation of the Patent, or its limitation to the extent that Levofloxacin would no longer have been protected by the claims. Secondly, there is a free standing attack on the SPC (or its duration) based upon earlier marketing authorisations for ofloxacin.

Generic player Generics UK challenged the patent validity based on obviousness and cited following articles as prior art:

1) EP 0,047,005 ("the 005 Patent").

2) DL-8280, Drugs of the Future, vol 8, no. 5 (1983) pp. 395-396 ("Drugs of the Future").

3) EP application No. 0225552

4) An abstract entitled "Synthesis and antibacterial activity of the optical isomers of 6,7-dihydro-9-fluoro-5-methyl-1-oxo-1H, 5H-benzo[ij] quinolizine-2carboxylic acid (flumequine)" by Gerster et al, (Proceedings of the North American Medicinal Chemistry Symposium, Toronto, 153 (1982)) ("Gerster I").

5) A paper entitled "Differentiation of fluorinated quinolone antibacterials with Neisseria gonorrhoea isolates" by Rohlfing et al, (Journal of Antimicrobial Chemotherapy, 15, 539-544) ("Rohlfing").

6) A poster said to be that of Dr Gerster at the 1982 Toronto symposium to which the Gerster I abstract relates ("Gerster IP"). There is a factual issue as to whether Gerster IP was made available to the public.

7) A paper entitled "Stereochemical aspects of the antibacterial activity of S-25930" by Gerster et al, (25th Interscience Conference on Antimicrobial Agents and Chemotherapy, Minneapolis, 29 September – 2 October 1985) ('Gerster II'). Gerster II only becomes relevant if the Patent is not entitled to its first priority date of 20 June 1985.

The Court of Appeal dismissed the appeal and opined that the person having ordinary skilled in the art during development of Levofloxacin would have tried to resolve enantiomer of Ofloxacin, however, the skilled person could have tried to explore resolution up to a certain points. However, unexpected results like better solubility, lesser toxicity and decreased dose in comparison to Ofloxacin suggest that invention is not obvious and court opined that claim 1-2 and 5-7 of disputed patent are not invalid.

Opinion of court http://www.bailii.org/cgi-bin/markup.cgi?doc=/ew/cases/EWHC/Patents/2008/2413.html&query=levofloxacin&method=boolean

Vardenafil Hydrochloride (Levitra) 2.5 mg, 5 mg, 10mg and 20 mg tablets: Innovator Bayer sued Teva in a bid to block generic version

Innovator Bayer has sued generic player Teva in US district court for the district of Delaware in a bid to block generic version of Vardenafil Hydrochloride (Levitra) 2.5 mg, 5 mg, 10 mg and 20 mg tablets.

Innovator has sued Teva for the infringement of following Orange Book listed patent:

US6362178 (Expiry: Oct 31, 2018): Which covers a method of treating chronic heart failure or erectile dysfunction, comprising administering to a mammal an effective amount of various PDE-V inhibitors like Vardenafil.

Possibly, generic player Teva has filed Paragraph IV certification with invalidation grounds against said patent. As innovator has sued Teva with in 45 days after the receipt of Para IV lettr, accordingly, Teva's ANDA approval process would be delayed by 30 month as per Hatch-Waxman provisions.

Innovator Bayer got approval to market Vardenafil Hydrochloride (Levitra) 2.5 mg, 5 mg, 10mg and 20 mg tablet on Aug 19, 2003. The New Chemical Entity exclusivity of this product has already expired on Aug 19, 2008.