Friday 29 August 2008

Galantamine Hydrobromide (Razadyne): Barr Announces Favorable Ruling in Patent Challenge, USFDA grant final approval with 180 days exclusivity to Barr

Barr Pharma announced that the U.S. District Court of Delaware has delivered favorable ruling in the challenge of innovator Ortho McNeil Janssen's Orange Book listed patent w.r.t Razadyne(Galantamine hydrobromide), 4 mg, 8 mg and 12 mg tablets
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.
The Court's decision will effectively end the 30-month stay with respect to Barr's generic Razadyne tablets and Barr's generic Razadyne ER (Galantamine hydrobromide), 8 mg, 16 mg and 24 mg extended release capsules. USFDA has given final approval to Barr’s ANDA on August 28, 2008, as per USFDA records (Orange Book).
The '318 patent was found to be invalid for lack of enablement. The Judge also denied Janssen's request for a Temporary Restraining Order, which would have prevented Barr from marketing its product.
The other patents listed for this product in Orange Book are as follows, which were not in litigation:
US6099863 (Expiry: Jun 6, 2017): which covers a tablet comprising as an active ingredient a therapeutically effective amount of galanthamine hydrobromide (1:1) and a pharmaceutically acceptable carrier, wherein said carrier comprises a spray-dried mixture of lactose monohydrate and microcrystalline cellulose (75:25) as a diluent, and an insoluble or poorly soluble cross-linked polymer disintegrant.
US6358527 (Expiry: Jun 6, 2017): which covers a method of treating a disorder selected from dementia, mania or nicotine dependence in a patient in need thereof comprising administering to the patient a tablet comprising as an active ingredient a therapeutically effective amount of galanthamine hydrobromide (1:1) and a pharmaceutically acceptable carrier, wherein said carrier comprises a spray-dried mixture of lactose monohydrate and microcrystalline cellulose (75:25) as a diluent, and an insoluble or poorly soluble cross-linked polymer disintegrant.
Barr filed an Abbreviated New Drug Application (ANDA) with the USFDA for Janssen's Razadyne (Galantamine hydrobromide), 4 mg, 8 mg and 12 mg tablets on February 28, 2005. On June 15, 2005, Barr announced that Janssen had filed suit in the District Court for the District of Delaware, and the trial occurred in May 2007.
Barr also has a pending ANDA for Razadyne ER (Galantamine hydrobromide), 8 mg, 16 mg and 24 mg extended release capsules. In its ANDA for that product, Barr certified that the '318 patent was invalid, unenforceable or not infringed. Barr subsequently amended its application to certify that an additional following Orange Book patent,
US7160559 (Expiry: Dec 20, 2019): which covers controlled release formulation containing galantamine as the active ingredient, characterized in that it comprises particles comprising galantamine hydrobromide (1:1), and a water soluble film forming polymer wherein the galantamine hydrobromide (1:1) and the water soluble film forming polymer are layered or coated on inert spheres, said particles being coated by a release rate controlling membrane coating wherein the release rate controlling membrane coating comprises a water insoluble polymer and optionally a plasticizer, and wherein the formulation further comprises a topcoat comprising galantamine and water-soluble polymer and wherein the formulation is capable of releasing in USP buffer pH 6.8 at 37.degree. C. in a paddle apparatus operating at 50 rpm, from 20 to 40% of the total amount of galantamine.HBr in 1 hour, and more than 80% of the total amount of galantamine.HBr in 10 hours.
The ‘559 patent was not listed at the time Barr's original ANDA was filed, was invalid, unenforceable or not infringed. Innovator Janssen sued Barr in the District Court of New Jersey on June 30, 2006. Pursuant to an Order in the case, Judge's decision in the District of Delaware will be given effect in the Razadyne ER litigation. Barr believes that, because the '559 patent was not listed at the time Barr's original application was filed, the decision with respect to the '318 patent will end the 30-month stay with respect to the generic Razadyne ER product.
Barr also announced that it would launch the product immediately in the US market with 180 days exclusivity. The other generic players would be able to market their product after the expiry of Barr’s 180 days exclusivity, from March 1 , 2009 onwards.
The other generic players who filed Para IV against Immidiate Release tablets are Sandoz, Par Pharmaceutical, Alphapharm, Purepac, Dr. Reddy's, Mylan and Teva
The other generic players who filed Para IV against Extended Release capsules are KV pharma and Sandoz
Razadyne tablets had annual sales of approximately $102 million for the twelve months ending June 2008, according to IMS sales data.
Razadyne ER capsules had annual sales of approximately $112 million for the twelve months ending June 2008, according to IMS sales data.
Also, innovator announced that it would challenge the district court’s decision in higher court

Copaxone (R) (Glatiramer acetate):Innovator Teva sued generic players Momenta and Sandoz

Teva Pharma has initiated efforts to block generic challenge on Copaxone(R) (Glatiramer acetate) after information of Para IV filings by generic players like Momenta and Sandoz.Teva received Momenta/Sandoz's Paragraph IV certification notice referring to following orange book listed patents
US5981589 (Expiry: May 24, 2014)- Covers Copolymer-1 having a molecular weight of about 5 to 9 kilodaltons, made by a process comprising the steps of: reacting protected copolymer-1 with hydrobromic acid to form trifluoroacetyl copolymer-1, treating said trifluoroacetyl copolymer-1 with aqueous piperidine solution to form copolymer-1, and purifying said copolymer-1, to result in copolymer-1 having a molecular weight of about 5 to 9 kilodaltons.
US6054430 (Expiry: May 24, 2014)- covers an improved composition of copolymer-1 comprising copolymer-1 substantially free of species having a molecular weight of over 40 kilodaltons.
US6342476 (Expiry: May 24, 2014)- covers an improved composition of copolymer-1 comprising copolymer-1 substantially free of species having a molecular weight of over 40 kilodaltons.
US6362161 (Expiry: May 24, 2014)- covers an improved composition of copolymer-1 comprising copolymer-1 substantially free of species having a molecular weight of over 40 kilodaltons.
US6620847 (Expiry: May 24, 2014)- Covers Copolymer-1 having a molecular weight of about 4 to about 9 kilodaltons, made by a process comprising: treating trifluoroacetyl copolymer-1 with aqueous piperidine to form a solution of copolymer-1; and purifying copolymer-1, thereby producing copolymer-1 having a molecular weight of about 4 to about 9 kilodaltons.
US6939539 (Expiry: May 24, 2014)- Covers A copolymer-1 composition comprising a mixture of polypeptides composed of glutamic acid, lysine, alanine and tyrosine, wherein the mixture has an average molecular weight of about 4 to about 9 kilodaltons, wherein the mixture of polypeptides is non-uniform with respect to molecular weight and sequence, and wherein the composition is suitable for treating multiple sclerosis.
US7199098 (Expiry: May 24, 2014)- Covers a copolymer-1 composition comprising a mixture of copolymers of alanine, glutamic acid, lysine and tyrosine, the copolymer species in the mixture being non-uniform with respect to molecular weight and sequence, wherein over 75% of the copolymers in the mixture, on a molar fraction basis, have a molecular weight in the range of 2 kDa to 20 kDa and less than 5% of the copolymers have a molecular weight above 40 kDa, and wherein the composition is suitable for treating multiple sclerosis.
The lawsuit, filed in U.S. District Court in Manhattan, claims that any generic version of Copaxone infringes patents that Teva contends are valid and enforceable.
Teva believes designing around 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.Glatiramer Acetate is the generic name for Copaxone or Copolymer. It is an immunomodulator, licensed in much of the world for reduced frequency of relapses in relapsing-remitting multiple sclerosis. Copaxone is administered by subcutaneous injection at a dose of 20 mg per day. It is a non-interferon and non steroidal medication.Glatiramer acetate was originally discovered by Professor Sela, Professor Arnon and Dr. Teitelbaum at the Weizmann Institute of Science in Israel. Teva got license on this molecule and subsequently commercialised this product.
Teva is till date best IP designing around Pharmaceutical company and now it will be interesting to watch Teva's Defense as innovator.
(Note: Updated earlier news on Glatiramer acetate)


Taro Takeover: Sun Pharma got favorable ruling

Sun pharma is with in striking disance w.r.t its deal on buying Israeli generic player Taro Pharma. A district court in Tel Aviv has sided with Sun pharma on Taro’s tender issue.
The rejection of Taro’s plea will prompt Sun to acquire 12 % stake of the Israeli company’s chairman Barrie Levitt and his family members at $7.75 a share.
Sun Pharma's Hungarian subsidiary Alkaloida offered to acquire shares of Taro, including that of the promoters, as part of an option agreement, which was signed earlier between Sun and Taro during the merger talks. That agreement gives Sun Pharma an option to acquire the promoters’ stake, in the event of a failed merger.
Earlier, the US Federal Trade Commission (FTC) had given green signal to Sun to acquire Taro Pharmaceuticals, after the regulator forced the Indian generic company to sell off three of its drugs to Torrent Pharmaceutical, to avoid a monopolistic situation in the US market.

However, Sun Pharma may face legal battles in New York courts in its attempt to take over, unless its chairman Barrie Levitt and family give up in a few weeks. Also, it will be interesting to watch whether Taro challenge the District Court's decision in the Israeli Supreme Court. (Source: Business standard)

Tuesday 26 August 2008

Oxymorphone Hydrochloride (Opana ER): Innovator sued Sandoz for Para IV filing

Innovator Endo Pharma and Penwest Pharma have accused Sandoz of patent infringement in their third suit to keep a generic version of painkiller Opana ER (Oxymorphone Hydrochloride) off the market. Following patents are listed in orange book for this product
US5128143 (Expiry: Sep 19, 2008): Covers a slow release pharmaceutical excipient of an inert diluent and a hydrodrophilic material including xanthan gum and a galactomannan gum capable of cross-linking the xanthan gum in the presence of aqueous solutions.
US5662933 (Expiry: Sep 9, 2013) which covers a sustained release pharmaceutical formulation and methods of making and using the same. The sustained release pharmaceutical formulation includes a sustained release excipient including a gelling agent, an inert pharmaceutical diluent, an optional hydrophobic material and/or hydrophobic coating, and a medicament for sustained oral administration.
US5958456 (Expiry: Sep 9, 2013) which covers a controlled release solid dosage form for oral administration of a therapeutically active medicament to a patient in need thereof, comprising: a pharmaceutically effective amount of a medicament to be administered to a patient in need of said medicament; a sustained release excipient comprising a gelling agent; a pharmaceutically acceptable hydrophobic material; and an inert pharmaceutical diluent wherein the ratio of said inert diluent to said gelling agent is from about 1:8 to about 8:1, said dosage form providing a sustained release of said medicament when exposed to an environmental fluid.
US7276250 (Expiry: Jul 3, 2022) which covers an oral sustained release formulation comprising from about 5 mg to about 80 mg oxymorphone hydrochloride and from about 80 mg to about 360 mg of a granulated sustained release delivery system, wherein the granulated sustained release delivery system comprises from about 8.3% to about 41.7% by weight locust bean gum, from about 8.3% to about 41.7% by weight xanthan gum, from about 20% to about 55% by weight dextrose, from about 5% to about 20% by weight calcium sulfate dihydrate, and from about 2% to about 10% ethyl cellulose.
Innovator is already in litigation with Actavis and Impax on this product as reported earlier by IPPHARMADOC Here

Clozapine (FazaClo) Orally Disintegrating Tablets, 25mg and 100mg:Barr Confirms Patent Challenge aiming 180 days exclusivity

Barr Pharma has initiated a challenge of the Orange Book listed patents byAzur Pharma w.r.t FazaClo(R) (clozapine) orally disintegrating tablets, 25mg and 100mg. Following patents are listed for this product:
US5178878 (Expiry: Jan 12, 2010): which covers a solid pharmaceutical dosage form adapted for direct oral administration to a human comprising: a mixture of at least one saliva activated effervescent agent and a plurality of microparticles, each said microparticle including at least one systemically distributable pharmaceutical ingredient and a protective material substantially encompassing said pharmaceutical ingredient, said microparticles having at least about 70 percent 30-minute release, said mixture being present as a tablet of a size and shape adapted for direct oral administration to a human patient, said tablet being substantially completely disintegrable so as to release said microparticles upon exposure to saliva, said at least one effervescent agent being present in an amount which is effective to aid in rapid disintegration of said tablet, without chewing, and thereby release said microparticles.
US6024981 (Expiry: Apr 9, 2018): which covers a hard, compresed, rapidly dissolvable dosage form adapted for direct oral dosing comprising: an active ingredient and a matrix including a non-direct compression filter and a lubricant, said dosage form being adapted to rapidly dissolve in the mouth of a patient and thereby liberate said active ingredient, and having a friability of about 2% or less when tested according to the U.S.P., said dosage form having a hardness of at least about 15 Newtons.
US6106861 (Expiry: Dec 5, 2017): which covers a multiparticulate tablet disintegrating in the mouth in less than 40 seconds and comprising an excipient and an active ingredient in the form of microcrystals comprising a taste-making coating wherein the excipient comprises, with respect to the mass of the tablet, from 3 to 15% by weight of at least one disintegration agent selected from the group consisting of cross-linked polyvinylpyrrolidone and cross-linked carboxymethylcellulose and from 40 to 90% by weight of at least one soluble diluent agent with binding properties consisting of a polyol having less than 13 carbon atoms, said polyol being either in the directly compressible form which is composed of particles whose average diameter is from 100 to 500 micrometers or in the powder form which is composed of particles whose average diameter is less than 100 micrometers, said polyol being selected from the group consisting of mannitol, xylitol, sorbitol and maltitol, with the proviso that, when only one soluble diluent agent with binding properties is used, it is a polyol in the directly compressible form except sorbitol and, when at least two soluble diluent agents with binding properties are used, these are consisting of the same polyol, one part of which is in the directly compressible form while the other part is in powder form, the proportion of directly compressible polyol to powder polyol being from 99/1 to 50/50 and the coating of the microcrystals of active ingredient comprises at least one coating agent selected as a function of the physico-chemical characteristics of the active ingredient selected from the group consisting of polymethacrylates and cellulose polymers and combinations thereof with each other.
US6221392 (Expiry: Apr 9, 2018): which covers a hard, compressed, rapidly dissolvable dosage form adapted for direct oral dosing comprising: an active ingredient and a matrix including a nondirect compression filler and a lubricant, said dosage form being adapted to rapidly dissolve in the mouth of a patient and thereby liberate said active ingredient, and having a friability of about 2% or less when tested according to the U.S.P.

The Barr pharma has designed around the said formulation patents. Also, Barr will be entitled for first to file 180 days exclusivity on this product.

Monday 25 August 2008

Azelastine: Meda settled patent dispute with Cobalt

Innovator Meda has settled the patent infringement case against generic player Cobalt on Azelastine (4-[(4-chlorophenyl)methyl]-2- (1-methylazepan-4-yl)-phthalazin-1-one). Both companies were in litigation since July 2007, after Cobalt submitted ANDA. Azelastine is an antihistamine and mast cell stabilizer available as a nasal spray (Astelin®) for hay fever and as eye drops (Optivar®) for allergic conjunctivitis. The following patent is listed in orange book for Optivar (azelastine opthalmic solution) and Astelin (azelastine Nasal spray)
US5164594 (Expiry: May 1, 2011): which covers a method for the treatment of irritation or disorders of the nose and eye which comprises applying directly to nasal tissues or to the conjunctival sac of the eyes a medicament which contains a member selected from the group consisting of azelastine and its physiologically acceptable salts.
Under the settlement agreement, Cobalt admitted infringement of Meda's ‘594 patent. The settlement agreement allows Cobalt to launch a generic version of Astelin, under a license from Meda, on 28 August 2010 at the earliest. Importantly, Cobalt will pay 32.5% of their net sales of this product to Meda until 1 February 2011.
Earlier, innovator settled with Apotex on same product as reported earlier by IP Pharma doc here
However, litigation is pending with Sun pharma on Optivar.

Atorvastatin (Lipitor) : Pfizer’s sale on decline after generic launch in Korea

Global pharmaceutical giant Pfizer’s domestic market share of its top seller Lipitor slipped nearly 15 percent in just one month after local drugmakers released generics of the cholesterol-lowering pill in June. But the head of the Korean operation isn’t sweating over it.
Earlier in June, 5 generic firm, got positive opinion from Korean court on Lipitor launch. The court thwarted innovator’s patent ever greening attempts, as reported earlier by IPPHARMADOC Here
Full story Here

Generic threat: if you can’t beat them, buy them

The offer period is underway for Japanese pharma giant Daiichi Sankyo’s bid for Ranbaxy lab. Daiichi plans to acquire 20% of the firm in the open market, with private deals making up the rest of its eventual majority stake. The offer forms part of a trend in which established drugs firms deal with the threat of developing-world generics firms by buying, or copying, them. Another approach is to launch authorized generic to affect the sale of generic competitor.

Complete article Here
Earlier article of IPPharmadoc on his issue Here

Lupin buy stakes in Australian firm Generic Health

Indian generic firm Lupin announced has bought stake in Australian generic firm Genric health for undisclosed amount. Generic health delas in OTC products and the said stake will consolidate Lupin’s generic entry into lucrative Australian market

Friday 22 August 2008

Trusopt (Dorzolamide) & Cosopt (Dorzolamide & Timolol): CAFC thwart Apotex’s attempt for triggring generic rival Hi-tech’s 180 days exclusivity

Court Of Appeals For Federal Circuit (CAFC) in asignificant decision thwarted Apotex’s attempt for triggring generic rival Hi-tech’s 180 days exclusivity on Dorzolamide. Hi-tech was first ANDA filer for Trusopt (Dorzolamide) & Cosopt (Dorzolamide & Timolol) by filing Para IV against following Orange Book listed patents on Oct 11, 2005.
US4797413 (Expiry: Oct 28, 2008)
US 6248735 (Disclaimed)
US 6316443 (Disclaimed)
On january 18, 2006 innovator Merck sued Hi-tech for the infringement of ‘413 patent (the other two patents were disclaimed by innovator under 35 USC 253) .
On April 2006, court gave decision in favor of innovator Merck (which was also affirmed by CAFC on March 29,2007) and delayed ANDA proval of Hi-tech till expiry of ‘413 patent. However, Hitech got 180 days exclusivity based on Para IV filing aagiants ‘735 and ‘443 patents.
Apotex also filed ANDA against innovator’s Orange Book listed patent ‘413 but it also sought to file Para IV against ‘735 and ‘443, which were disclaimed by innovator at the time of Apotex’s ANDA filing. Apotex was sued by innovator on December 4, 2006 for he infringement of ‘413 patent. However, apotex counter claimed for declaratory judgment of noninfringement/invalidity w.r.t disclaimed patents ‘735 and ‘443.
The CAFC concluded that there is no article III controversy and dismissed Apotex’s complaint and its attempt to trigger Hitech’s 180 days exclusivity
Trusopt (dorzolamide hydrochloride ophthalmic solution) is a carbonic anhydrase inhibitor formulated for topical ophthalmic use. Trusopt is used to lower increased intraocular pressure in open-angle glaucoma and ocular hypertension.
Cosopt (Dorzolamide hydrochloride & Timolol maleate) is a drug for lowering pressure in the eye to normal levels, and a treatment for glaucoma.
Opinion of court

Drug approvals: Pliva (Pamidronate Disodium Injection), Actavis (Bupropion Hydrochloride)

Pliva (Pamidronate Disodium Injection)
Pliva( subsidiary of Barr) has received final approval from the USFDA for its generic version of Hospira's Pamidronate Disodium Injection, 30mg/10mL, 60mg/10mL, and 90mg/10m
Actavis (Bupropion Hydrochloride)
Actavis received approval from the USFDA to market Bupropion Hydrochloride extended-release tablets (XL) 300mg. The distribution of the tablets will commence immediately.

Thursday 21 August 2008

Omeprazole delayed release capsules (10, 20, 40 mg): Apotex and Impax’s Designing around strategies foiled

U.S. a Court of Appeals For federal circuit (CAFC) Upheld an infringement finding against generic Players Apotex and Impax on Wednesday in a case brought by AstraZeneca to defend the following formulation patents for its popular heartburn drug Prilosec (Omeprazole).
US4786505 (expiry: Oct 20, 2007): which covers an oral pharmaceutical preparation comprising (a) a core region comprising an effective amount of a material selected from the group consisting of omeprazole plus an alkaline reacting compound, an alkaline omeprazole salt plus an alkaline reacting compound and an alkaline omeprazole salt alone; (b) an inert subcoating which is soluble or rapidly disintegrating in water disposed on said core region, said subcoating comprising one or more layers of materials selected from among tablet excipients and polymeric film-forming compounds; and (c) an outer layer disposed on said subcoating comprising an enteric coating.
US4853230 (expiry: Oct 20, 2007): which covers an pharmaceutical preparation comprising: (a) an alkaline reacting core comprising an acid-labile pharmaceutically active substance and an alkaline reacting compound different from said active substance, an alkaline salt of an acid labile pharmaceutically active substance, or an alkaline salt of an acid labile pharmaceutically active substance and an alkaline reacting compound different from said active substance; (b) an inert subcoating which rapidly dissolves or disintegrates in water disposed on said core region, said subcoating comprising one or more layers comprising materials selected from the group consisting of tablet excipients, film-forming compounds and alkaline compounds; and (c) an enteric coating layer surrounding said subcoating layer, wherein the subcoating layer isolates the alkaline reacting core from the enteric coating layer such that the stability of the preparation is enhanced.
Impax tried to prove non-infringement on various grounds first that their formulation do not contain inert core, and the application of disputed patent was filed after one year of discovery, there is no article III controversy as disputed patents has expired. However, court refuted all the claims of Impax w.r.t noninfringement and inavlidty of disputed patents.
Earlier, CAFC in a decision in June 2008 gave favorable non-infringement opinion to another generic player Mylan’s as reported earlier by IPPHARMADOC Here
Mylan successfully designed around against innovator Astra’s Orange Book listed patents by using Talc in the coating. However, non-infringement strategy adopted by Apotex and Imapx was infringing and District court as well as CAFC upheld infringement.
Apotex’ formulation contains pallets with Povidone (PVP), magnesium hydroxide and mannitol. Apotex applies to pallet core an enteric coating of water, Methacrylic acid copolymer (MACP) and triethyl citrate. This strategy as per Apotex was non-infringing as there was no sub coat is involved but the testimony of innovator's expert Dr Davies led to the conclusion that reaction of PVP and MACP resulted into the formation of subcoat which was confirmed by Confocal laser scanning microscopy (CLSM). The expert successfully proved in the court that subcoat is present in Apotex formulation.

Regarding claim construction of disputed terms, specifically the meaning of the term alkaline Reacting compound (ARC) and acid labile. The CAFC rejected Apotex's claim that ARC was limited to salts from Groups I and II of the periodic table, finding that it was contrary to the specification of the '230 patent and claim 8, which included within the scope of the term ammonium salts also. Further, the term acid labile, the Court interpreted the cited prior art to disclose acid-stable compounds that did not anticipate the claims at issue.
Also, generic player’s attempt to invalidate formulation patents of Astra in the light of KSR v.s Teleflex decision and strong prior art was not accepted by the court
Importantly, the disputed patents have already expired.
As the generic manufacturer has entered into the market at risk since last five years, the decision allows AstraZeneca to seek compensation from Impax, Apotex and Impax's partner, Teva, for any sales they made when the patents were in force.

Wednesday 20 August 2008

Venlafaxine HCl (Effexor ER Capsules): Innovator sued Apotex for filing Paragraph IV

Innovator Wyeth has sued generic competitor Apotex for filing Paragraph IV certification against Orange Book listed patents of Wyeth's anti-depression drug Effexor ER Capsules 37.5, 75 and 150 mg (venlafaxine HCl). Following patents are listed in Orange Book w.r.t Venlafexine XR 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
Innovator has sued Apotex for the infringement of ‘171, ‘120 and ‘958 patents.
Other generic players in litigation : Anchen Pharmaceuticals, Lupin, Sandoz, Mylan, Wockhardt, Biovail
Recently innovator has already settled with Impax , Sun pharma and Teva on this product. Earlier news of pharmadoc Here

Biogenerics: Opportunity v.s Threat

The generic companies are eyeing the potential of biogenerics, as the market for generic products is declining due to the rising costs and more competition. Biogenerics offer a tremendous scope for generic players to capture the unexplored lucarative market. It is estimated that by the end of 2010 nearly half of all new approved pharmaceuticals will be biopharmaceuticals and that $60-80 billion worth of biopharmaceuticals will be going off patent in the next few years. The manufacturing and processing of biogenerics is not an easy task and is a challenging field for generic manufacturer. Although Biognerics bill got positive opinion from European authorities, however, the same bill is under review in US market. Generic player, Dr. Reddy has also collaborated in the field of Biogenerics with various firms as reported earlier by IPPHARMADOC Here.
An article by Zelda Pickup and Andrew Whitworth CMS Cameron McKenna, published in pharmalicensing.com has highlighted the potential of biogenerics Here

Another takeover by Teva in Europe

After finalizing deal on Barr (Here, Here, Here), there are reports that Teva is now ready to take over Germany based generic firm Stada (Here).
Earlier, Teva pharma has buy Spainish generic player Bentley pharma (120 products in European market) for $360 million. With the acquisition Teva will further consolidte its generics business in Europe.

Tuesday 19 August 2008

Triaz ( Benzoyl peroxide wash): CAFC clarifies Article III

CAFC ruled that marking products with their applicable patents does not create enough controversy under Article III of the U.S. Constitution to sustain a declaratory judgment suit, upholding the dismissal of a complaint filed against Medicis by a generics manufacturer Prasco for getting noninfringement request.
Medicic got license for its product Triaz ( benzoyl peroxide wash). The patents are listed on the packaging material of the product. Generic player Prasco makes a generic version of said wash by the name Oscion.
In an attempt to avoid the cloud of potential infringement, Prasco filed a declaratory judgment for non-infringement of the listed patents. The case was dismissed for lack of declaratory judgment jurisdiction.

Opinion of court

Galantamine (Razadyne, 4, 8 and 12 mg/tablet): Innovator sued Sandoz for filing Para IV

Innovator ORTHO MCNEIL JANSSEN has sued Sandoz in Delaware District Court, after the generics maker filed an ANDA for Galantamine (Razadyne, 4, 8 and 12 mg/tablet), which is indicated to treat Alzheimer's disease. This drug was approved by USFDA on Feb 28, 2001.
Following are the orange Book listed patents on this product
US4663318 (Expiry: Dec 14, 2008)- which covers a 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
US6099863 (Expiry: Jun 6, 2017)- Which covers a tablet comprising as an active ingredient a therapeutically effective amount of galanthamine hydrobromide (1:1) and a pharmaceutically acceptable carrier, wherein said carrier comprises a spray-dried mixture of lactose monohydrate and microcrystalline cellulose (75:25) as a diluent, and an insoluble or poorly soluble cross-linked polymer disintegrant.
US6358527 (Expiry: Jun 6, 2017)- Which covers a method of treating a disorder selected from dementia, mania or nicotine dependence in a patient in need thereof comprising administering to the patient a tablet comprising as an active ingredient a therapeutically effective amount of galanthamine hydrobromide (1:1) and a pharmaceutically acceptable carrier, wherein said carrier comprises a spray-dried mixture of lactose monohydrate and microcrystalline cellulose (75:25) as a diluent, and an insoluble or poorly soluble cross-linked polymer disintegrant.
Other generic players in litigation:
Teva
Mylan
Dr. Reddy's
Barr
Alpharma
Purepac
Par

Thursday 14 August 2008

Naproxen Sodium ER tablets: District court opined willful infringement by Watson

The US District Court of Florida ruled that Watson's NSAID (non-steroidal anti-inflammatory drug) product Naproxen ((+)-(S)-2-(6-methoxynaphthalen-2-yl)propanoic acid ) Sodium ER tablets, the generic version of Naprelan(R), infringes Elan's patent US5637320 which covers a once-daily naproxen formulation for oral administration having a first portion of the naproxen as a multi-particulate pellet form, each pellet having a core of naproxen or a pharmaceutically acceptable salt thereof in association with an organic acid, the core being surrounded by a multi-layer membrane and optionally a second portion of naproxen formulated to release the drug promptly following oral administration.
The court has found willful infringement of said patentFor details Market watch

Ultram (Tramadol hydrochloride extended-release tablets: Innovator sued Impax for filing Para IV

Innovator Ortho-McNeil have filed suit for patent infringement in the United States District Court of Delaware against Impax for submitting ANDA with Para IV certification for Ultram (Tramadol hydrochloride extended-release tablets,100 mg).

Innovator has sued based on Para IV filing against Orange book listed patent US6254887 (expiry: May 10, 2014) which covers A controlled release preparation for oral administration contains tramadol, or a pharmaceutically acceptable salt thereof, as active ingredient.

Ultram was approved by USFDA on Sep 8, 2005 for 100, 200 and 300 mg/tablet. Innovator is already in litigation with Par pharma (First Para IV filer) for this product

Wednesday 13 August 2008

Pramipexole (Mirapex): Barr settled with innovator despite invalidating product patent, generic launch delayed

Barr Pharma announced that it has signed a settlement Agreement with innovator Boehringer Ingelheim to resolve the patent litigation w.r.t Mirapex Tablets (Pramipexole Dihydrochloride) 0.125mg, 0.25mg, 0.5mg, 1mg & 1.5mg.Following patents are listed in Orange Book for Pramipexole Dihydrochloride Tablets

US4886812 (Expiry: OCT 8, 2010)- Product patent (specific)

US6001861 (Expiry: JAN 16,2018)- method of use for restless leg syndrome

US6194445 (Expiry:JAN 16,2018)- method of use for restless leg syndrome

Earlier, the U.S. District Court for Delaware has invalidated the Orange Book listed product patent ‘812 of innovator. In a significant ruling, District Court Judge opined that the product claim in litigation is invalid because of double patenting.

Earlier, Barr received notification of the application's acceptance for filing in July 2005. Following receipt of the notice from the USFDA, Barr notified Boehringer Ingelheim, the New Drug Application (NDA) holder and patent owner. On September 26, 2005, Boehringer Ingelheim filed suit in the U.S. District Court in Delaware to prevent Barr from proceeding with the commercialization of its product, formally initiating the patent challenge process under the Hatch-Waxman Act.Also, in Feb 2008, Barr got final approval on its ANDA but decided not to launch the product until decision from CAFC.

Importantly, Barr has got First to file exclusivity on this product and with favorable ruling from District court, Barr could have launched the product immediately, but Barr decided to settle with the innovator as Barr was reluctant to face the trial in Court of Appeal for Federal Circuit (CAFC). Under the agreement Barr will launch its product on January 1, 2010 (10 months earlier than the product patent expiry). The other generic companies can launch their product from July 1, 2010 (If any generic company invalidate innovator’s product patent in CAFC) otherwise from October 9, 2010.
Pramipexole was approved by USFDA on July 1, 1997. Barr has got final approval on February 19, 2008 and Mylan has got tentative approval on May 8, 2007.

Earlier, innovator has also sued Mylan for '812 parent and is in talk with Mylan for the settlement on this case.
Nowadays, generic companies prefer to have certainty of product launch without undue litigation expenses. This settlement is favorable for the Barr as it will have almost 10 months exclusivity (may be with Mylan) in the market and also for innovator as its product patent will remain in force and will act as barrier for other generic companies.
In addition, Barr Laboratories also entered into a Settlement to resolve the patent litigation regarding Boehringer Ingelheim's Aggrenox (Aspirin (25mg)+Dipyridamole 200 mg) extended release capsules, which will be launched as authorized generic version from July 1, 2015 onwards.

Earlier news of Ippharmadoc Here

Tuesday 12 August 2008

Clopidogrel Bisulfate (Plavix): Former Bristol-Myers Squibb (BMS) Vice-President Charged With Lying About patent deal

A false information submitted to regulatory or federal agency to get approval or monetary benefit for the company can be detrimental for the employee who sign or submit the wrong information.
Andrew Bodnar, a former senior vice-president of BMS, was indicted for his role in lying to the federal government about a patent deal on Clopidogrel Bisulfate (Plavix). The said official provided false information to Federal Trade Commission (FTC) about BMS’s deal with Apotex to delay generic launch till 2011. On 8th August 2006, Clopidogrel was launched by Apotex at risk of infringement of Product patent and after preliminary injunction opinion in favor of innovator on 31st August 2006, Apotex stopped the sale. Later on, Apotex settled with the innovator and agreed to launch generic version in 2011, innovator in turn agreed to stop authorized generic launch of Clopidogrel. The details of settlement provided to FTC by Apotex and BMS were not same and from Apotex's documnets FTC concluded that BMS official submitted false statement. The details are Here
The latest FDLI REVIEW ARTICLE highlights the same issues.

Alendronate Sodium trihydrate: 10 generic players in US market

Indian Pharma giant Dr. Reddy's Lab has received final approval from the USFDA to market Alendronate sodium trihydrate tablets. Following generic players have got final approval to market this blockbuster drug.

1) Teva
2) Barr
3) Mylan
4) Watson
5) Cobalt
7) Apotex
8) Genpharm
9) Dr. Reddy
10) Aurbindo
11) Ivax (Tentative approval)

Earlier, Teva and Barr got 180 days exclusivity, which started on Feb 6, 2008 and expired on August 3, 2008. Most of the generic player (excluding Barr and Teva) got final approval on August 4, 2008.

Monday 11 August 2008

Atorvastatin (Lipitor): Apotex settled with Pfizer

After settling with Ranbaxy on Lipitor (Atorvastatin hemicalcium trihydrate), Pfizer has settled all pending patent litigation with Candian pharma giant Apotex (for Canadian market). Pfizer reported the above settlement as per information filed with the U.S. Securities and Exchange Commission. Pfizer said they agreed to settle with Apotex in July, but did not disclose terms of the agreement. Pfizer said the settlement agreement is subject to certain conditions.

Earlier in January 2008, a Canadian Federal Court denied Pfizer's request to prevent Apotex from launching a generic version of Lipitor prior to the expiration of a Pfizer patent in July 2010. On January 3, 2008, Pfizer appealed the decision to the Federal Court of Appeal of Canada.
Further, Apotex like Ranbaxy thought of certainty of Atorvastatin generic launch in Canada without the fear litigation and treble damages on process, polymorph, formulation and intermediate patents with Pfizer.
Lipitor is the best examples of patent protection by innovator Pfizer. Importantly, Pfizer has snubbed the generic challenge till product patent expiry in US and Canada.
Earlier news of Ippharmadoc on lipitor Here





Famciclovir: Novartis sued Roxane for changing certification from Para III to Para IV against product patent

Innovator Novartis sued Roxane pharma for the Infringement of orange book listed patent US5246937 on Famvir® (famciclovir) following change in certification as part of Roxane's filing of an ANDA. Earlier, CAFC has invalidated the same patent on complaint from Teva. After the invalidation of ‘937 patent Roxane has changed its certification from Para III to Para IV (Earlier Roxane filed Para III against said patent). Also, Roxane was sued on method of use patents lised in orange book. The above lawsuit is second against Roxane for the said product.
Following patents are listed in orange book for this product
US5246937 (Expiry: Sep 21, 2010)- which covers purine derivatives like Famciclovir as product
US5840763 (Expiry: Sep 1, 2015)- Method of use for herpes viral infection
US5866581 (Expiry: Oct 4, 2014)- Method of use for post-herpetic neuralgia
US5916893 (Expiry: Sep 1, 2015)- Method of use for latent infection of herpesviruses
US6124304 (Expiry: Oct 4, 2014)- method of use for the treatment of zoster associated pain
Teva has approved ANDA for 125 mg, 250 mg and 500 mg tablets, the ANDA was approved on August 24, 2007. (Link to earlier news from IPPHARMADOC)

CIP-ISOTRETINOIN: Ranbaxy sign agreement with Cipher

Cipher Pharma announced that it has entered into a definitive development, distribution and supply agreement with Ranbaxy Pharma, under which Cipher has granted RPI the exclusive right to market, sell and distribute CIP-ISOTRETINOIN in the United States, its territories and possessions. For full story link to Smartbrief

Clopidogrel: Generic to be 25% cheap in comparison to innovator in Germany

Novartis AG’ generic unit Hexal will sell a generic version of Sanofi-Aventis SA's Plavix blood-thinner at a discount of about 25 % in Germany. Link
Earlier news of IPPharmadoc on Clopidogrel Here

Friday 8 August 2008

section 271(e)(1) safe harbor provision: CAFC favor patentee Proveris

The U.S. CAFC ruled that the manufacture, marketing, or sale of a medical device in US market, which is used in the development of USFDA regulatory submissions, but is not part of the USFDA’s premarket approval process, is not entitled to the protection of the Hatch-Waxman Act section 271(e)(1) safe harbor provision.
The case pertains to US6785400 (Assignee: Proveris), which covers a spray data acquisition system comprising: a housing for supporting a pumping device whereby the pumping device is responsive to an applied force to generate an aerosol spray plume through an exit port thereon along a spray axis; a spray pump actuator, wherein the spray pump actuator is capable of controlling a pumping force and a duration of the aerosol spray plume of the pumping device; an illumination device for illuminating the aerosol spray plume along at least one geometric plane that intersects the aerosol spray plume; and, an imaging device for acquiring data representative of a first interaction between the illumination and the aerosol spray plume along the at least one geometric plane.
Innova manufacture Optical spray analyzer (OSA) which is used to calibrate spray based medication and the same device is used by USFDA to optimize the spray pattern of new drugs and generics. The suit was filed way back in 2005 in district court of Massachusetts, District court concluded that OSA infringe ‘400 patent and safe harbor provision are not applicable to OSA device.
The court concluded that section 271(e)(1) provides no such immunity,and Hatch Waxman act did not signify any advantage under section 271(e) to parties like Innova, whose device is not subject to USFDA premarket approval.
The CAFC further affirmed district court’s decision (Proveris Scientific Corp. v. Innovasystems: Opinion of court)

Wednesday 6 August 2008

Alendronate Sodium: Aurbindo got final approval

Hyderabad based Aurbindo Pharma has announced that the company has recieved final approval to market Alendronate Sodium trihydrate tablets (Generic equivalent of Merck's Fosamax) for 10mg, 35mg and 70mg. Alendronate Sodium trihydrate is indicated for the treatment of osteoporosis. Aurbindo is the first company to recieve approval after the expiry of combined 180 days exclusivity of Barr and Teva (which ended on 6th August). The Aurbindo's ANDA was reviewed with in 8 months by USFDA. Eralier, Barr and Teva launched their product in February, 2008, after the expiry of product patent.

Tuesday 5 August 2008

New Paragraph IV filings till July 22, 2008

1. Coreg CR®(Carvedilol) Extended Release Capsules 10 and 20mg on March 18, 2008
2. Seroquel XR®(Quetiapine) ER Tablets 200 and 300mg on June 12, 2008
3. Vfend®(Voriconizole) Tablets 50 and 200mg on April 14, 2008
4. Fazaclo®(Clozapine) Orally Disintegrating Tablets 25 mg and 100 mg on April 28, 2008
5. Copaxone®(Glatiramer) Injection 20 mg/mL, 1mL pre-filled syringe on December 27, 2007
6. Axid®(Nizatidine) Oral Solution 15 mg/mL on May 14, 2008
7. Temodar®(Temozolomide) Capsules 140 mg and 180 mg on March 24, 2008
8. Osmoprep®(Sodium Phosphate Monobasic Monohydrate and Sodium Phosphate Dibasic Anhydrous) Tablets 1.102 g and 0.398 g on April 9, 2008
(Source: USFDA)

Dynapar (Diclofenac, Paracetamol) :Gujarat High Court has upheld the design patent

In a significant Judgement, Gujrat high court has upheld the design patent of Dynapar tablets(Diclofenac, Paracetamol) , manufactured by Troikaa Pharma. The said ruling will prohibit generic manufacturer like Pro labs to use similar shape, size and color of the Dynapar tablet in India. (for full article Link to Economictimes)

Monday 4 August 2008

USFDA started surprise inspection of approved plants in India

USFDA has started inspecting carefully the generic facility in India and China. After opening the offices in China, USFDA is all set to establish their offices in India. Also, Pharmabiz has reported that US regulatory agency has commenced surprise inspections of all its approved facilities in India. In India there are more than 110 USFDA approved plants.

Recently, some senate members and NGO's in US are criticizing FDA for not using adeqate measures to check flow of substandard generics from Asia.

Saturday 2 August 2008

Biotech companies hit by patent ruling in UK

The biotech companiesies got a negative decision by the UK High Court in a decision that may set a higher threshold for intellectual property protection.
Eli Lilly applied to revoke European, held by the defendant HGS. The Patent discloses the nucleotide and amino acid sequence of a novel member of the TNF ligand superfamily which it calls Neutrokine-a. The application for the Patent was filed on 25 October 1996 and it was granted on 17 August 2005. It is currently under opposition in the EPO. Oral proceedings took place before the Opposition Division in June 2008 and the Patent was revoked, apparently on the basis that the claimed invention lacked any inventive step and constituted a claim to an arbitrary member of the TNF ligand superfamily without a known function. The Opposition Division declined to provide further reasoning during the oral proceedings and a written decision is awaited. HGS intends to file an appeal and the decision of the Opposition Division will be suspended in the meantime.
The court opined that the Patent is invalid for lack of industrial applicability, insufficiency and obviousness. Whatever the merit of the discovery of Neutrokine-a, the specification contains no more than speculation about how it might be useful. It does not teach the person skilled in the art how to solve any technical problem and its teaching as to the range of applications of Neutrokine-a is implausible. Moreover, the claims to therapeutic and diagnostic products are insufficient in any event.
(Link to CourtOpinion)
(Link to full article by Financial times)

Friday 1 August 2008

Divalproex Sodium (Depakote delayed-release tablets): USFDA Approved generic version after the patent expiry

The USFDA has approved the generic versions of Depakote delayed-release tablets (Divalproex sodium) after the following orange book listed patents expired on 29th July,2008.
US4988731: which covers diethyl- or dipropylacetic acid salts of sodium valproate which have physiological properties similar to those of valproic acid or sodium valproate but show highly superior stability characteristics.
US5212326: Which covers Sodium hydrogen divalproate oligomer
The following generic players have received approval to market divalproex sodium delayed-release tablets:
1) Sun Pharma
2) Genpharm
3) Nu-Pharm
4) Upsher-Smith Lab
5) Sandoz
6) TEVA Pharma
7) Dr. Reddy’s Lab
8) Lupin
These generic versions of divalproex sodium delayed release 125 mg, 250 mg and 500 mg (Valproic acid activity) tablets are bio-equivalent to Depakote ® delayed release tablets distributed by Abbott Laboratories.
Earlier news from IPPharmadoc on this product Here , Here, Here, Here and Here







Carvedilol (Coreg): Teva settled with Dr. Reddy on API patents

Teva Pharma has settled a suit seeking to block Dr. Reddy’s Lab from launching a generic version of GlaxoSmithKline's congestive heart failure drug Carvedilol. The lawsuits concern US6699997, US6710184, US7056942 and US7126008 all of which are owned by Teva and covers Carvedilol API. Earlier, in Junuary 2008, Teva settled with Taro over above patents. The Teva is still in litigation with Apotex and Zydus on these patents

Levocetirizine (Xyzal): Innovator sued Barr for Filing Para IV

Belgian drugmaker UCB SA and its U.S. partner, Sepracor Inc., have filed their fourth lawsuit against another generic player Barr Pharma in an effort to stave off a generic challenge to their antihistamine drug Xyzal (Levocetirizine). The lawsuit was filed in US district court for the Eastern District of North Carolina on July 30, 2008. UCB alleged that Barr pharma infringed the company's patent US5698558 (Expiry: September 24, 2012, which covers method of use of levocetrizine) for levocetirizine hydrochloride 5mg by filing an ANDA with USFDA. There is only one patent listed in orange book for this product.
US5698558 (Expiry: September 24, 2012)- This patent covers a method of treating the symptoms of seasonal and perennial allergic rhinitis in a human which comprises administering to a human in need of such symptomatic relief therapy an amount of (-) cetirizine, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, said amount being sufficient to alleviate or palliate said allergic rhinitis.
The Company filed its ANDA containing a paragraph IV certification against ‘558 patent in January 2008. Xyzal (levocetirizine dihydrochloride) had annual sales of approximately $74 million in the U.S., based on IMS sales data for the twelve month period ending May 2008.
Earlier, innovator has filed lawsuit against Synthon (first para IV filer), Sun Pharmaceuticals, SandozHere and Here

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Disclaimer: "IP Pharma Doc" blog is published for information purpose only. "IP Pharma Doc" blog contains no legal advice. I assume no legal responsibility for the views/information expressed here. “IP Pharma Doc” blog is my personal website and not edited by my employer, accordingly, no part of my blog should be attributed to my employer. All information on the present blog should be double checked for its accuracy and applicability. © Dr. Sarwal (2007)
 
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