Tuesday 31 March 2009

Gemcitabin (Gemzar): Generic players failed to invalidate process patent

In a significant Judgement by Hon'ble Judge MR. JUSTICE KITCHIN on the revocation case of EP0577303 which is owned by innovator Eli Lilly, the Judge held that the "The allegations of obviousness and insufficiency have not been made out. The Patent is valid and the action must be dismissed".


The judgement by Hon'ble Judge MR. JUSTICE KITCHIN can be read here.

Topiramate (Topamax) 25, 50, 100 and 200 mg tablets: Generic versions launched in US market

The USFDA has approved/tetatively approved ANDA’s filed by following generic players for generic launch of Topiramate (Topamax) 25, 50, 100, 200 mg tablets:
1. ROXANE
2. PAR PHARM
3. MYLAN
4. BARR
5. TEVA (link to Fox news Here on Teva's generic launch)

6. RANBAXY
7. CIPLA LTD
8. GLENMARK GENERICS
9. COBALT LABS INC
10. APOTEX
11. PLIVA HRVATSKA DOO
12. ZYDUS PHARMS (Pharmalive news Link on generic launch)

13. AUROBINDO PHARMA
14. TORRENT PHARMS
15. UNICHEM
16. LUPIN

17. Sun Pharma (press releaseon generic launch Here)

The approved generic forms are AB rated w.r.t innovator’s tablets. The final approval to some generic players who are first para IV filer like Mylan and Cobalt was given after the expiry of product patent covering Topiramate.
Earlier, generic companies like Mylan and cobalt were trying to erode the generic market much before the expiry of product patent US4513006, however, the final decision in litigation was in favor of innovator Ortho-McNeil and court (CAFC) concluded that ‘006 patent is valid and enforceable, accordingly, generic launch was delayed as reported earlier by IPPharmdoc Here. Also, the said patent was scheduled to expire in September, 2008, however, innovator got paediatric exclusivity for six months on this patent (as reported by IPPharmadoc Here) and generic launch was delayed till March 27, 2009.

Topiramate (2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate) is an anticonvulsant drug produced by Ortho-McNeil Neurologics, a division of Johnson & Johnson. Generic versions are available in Canada and were FDA approved in September 2006 .

Topiramate was discovered in 1979 by Drs. Bruce E. Maryanoff and Joseph F. Gardocki during their research work in McNeil Pharmaceutical.This drug is used to treat epilepsy in both children and adults. As per Wolters Kluwer Health (formerly NDC Health), Topiramate had sales over $3.2 billion for the 12 months ending February 28, 2009.

Friday 27 March 2009

Glatiramer acetate injection (Copaxone): USFDA refused Teva's Citizen Petition

The USFDA has rejected a Citizen Petition by Innovator Teva w.r.t its blockbuster formulation Glatiramer acetate injection (Copaxone) against generic approvals.

Earlier in July, 2008, generic players like Momenta Pharma and Sandoz announced (as reported by IPPharmadoc Here) Para IV patent challenge on Glatiramer acetate injection. Subsequently, Teva sued the generic players in U.S. District Court of Manhattan, accordingly, ANDA approval process of generic companies was stayed for 30 months under Hatch-Waxman provisions.
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. Also, the mechanism of the drug product is not fully clear. Teva also 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.
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.. Copaxone had $1.38 billion in US sales in 2008.
Also, another generic player Mylan has opposed the Citizen petition by Teva.

Link to Globes news Here
Link to Foxbusiness news Here

Earlier news of IPPharmdoc on Copaxone Here

First to File Paragraph IV generic exclusivity for Eszopiclone, Erlotinib, Lanthanum Carbonate, Doxycycline: Mylan confirmed patent litigations

Pharma giant Mylan confirmed (in a press release Here) that Mylan and/or a subsidiary have been sued in connection with four separate "first-to-file" Paragraph IV Abbreviated New Drug Applications (ANDA) filed with the U.S. Food and Drug Administration (FDA).
1. Eszopiclone Tablets, 1 mg, 2 mg and 3 mg: Mylan and Alphapharm were sued by innovator Sepracor Inc. in the U.S. District Court of New Jersey in connection with the ANDA filing for Eszopiclone Tablets. Eszopiclone Tablets are the generic version of Sepracor's insomnia treatment Lunesta® Tablets, which had approximately $796 million in U.S. sales for the twelve months ending Dec. 31, 2008, according to IMS Health. (IP Pharma doc earlier review Here)
2.Erlotinib Hydrochloride (HCl) 25 mg, 100 mg and 150 mg Tablets: Mylan was sued by innovators OSI Pharma, Pfizer and Genentechin the U.S. District Court in Delaware in connection with the ANDA filing for Erlotinib Hydrochloride (HCl) Tablets, 25 mg, 100 mg and 150 mg. Erlotinib HCl Tablets are the generic version of OSI Pharmaceuticals' lung cancer treatment Tarceva® Tablets, which had approximately $492 million in U.S. sales for the twelve months ending Dec. 31, 2008, according to IMS Health. (IP Pharma doc earlier review Here)
3. Lanthanum Carbonate Chewable Tablets, 500 mg, 750 mg and 1000 mg: Mylan and Matrix were sued by innovators Shire (as reported by IP Pharma doc Here and Here) in the U.S. District Court for the Southern District of New York in connection with the ANDA filing for Lanthanum Carbonate Chewable Tablets, 500 mg, 750 mg and 1000 mg. Lanthanum Carbonate Chewable Tablets are the generic version of Shire's kidney disease treatment Fosrenol®, which had approximately $108 million in U.S. sales for the twelve months ending Dec. 31, 2008, according to IMS Health.
4. Doxycycline Delayed-release (DR) Capsules USP, 40 mg: Mylan was sued by innovator Galderma Lab, The Research Foundation of the State University of New York and New York University in the U.S. District Court of Delaware in connection with the ANDA filing for Doxycycline Delayed-release (DR) Capsules USP, 40 mg. Doxycycline DR Capsules are the generic version of Galderma's adult rosacea treatment Oracea® Capsules, which had approximately $82 million in U.S. sales for the twelve months ending Dec. 31, 2008, according to IMS Health. (IP Pharma doc earlier review Here)

Mylan believes it is among the first companies to have filed substantially complete ANDAs containing a Paragraph IV certification for three of these products and expects to be awarded 180 days of shared marketing exclusivity once final approvals are obtained. With Doxycycline DR Capsules, Mylan believes it could have sole marketing exclusivity for the 180 day period. Currently, Mylan has 118 ANDAs pending FDA approval, 33 of which are potential first-to-file opportunities.

Mylan to further strengthen stake in Matrix Lab

Mylan Inc. today announced (in a press release Here) its plans to purchase the remaining interest in Matrix Laboratories Limited from minority shareholders pursuant to a voluntary delisting offer. Mylan, through a wholly-owned subsidiary, currently owns approximately 71.2% of Matrix and controls more than 76% of its voting rights. The impact of the transaction is anticipated to be accretive to Mylan's 2009 earnings.

Thursday 26 March 2009

Omega-3-acid Ethyl Esters (Lovaza) 1 g capsules: Pronova received Paragraph IV notice letter from Apotex

Innovator Pronova BioPharma announced (in a press release) that Pronova and its U.S. marketing partner GlaxoSmithKline have received a Paragraph IV Notice in March, 2009 from Canadian Pharma giant Apotex advising that Apotex has submitted an Abbreviated New Drug Application (ANDA) to the USFDA for approval to market a generic version of Omega-3-acid Ethyl Esters 1 g capsules (Lovaza).

Apotex's notice letter states that its ANDA contains a Paragraph IV Certification alleging that the US5502077 (Expiry: Mar 26, 2013) and US5656667 (Expiry: Aug 27, 2018) patents are not valid, unenforceable, or will not be infringed by the commercial manufacture, use or sale of Par's product.

Also, Teva and Par has filed ANDA with Paragraph IV certification against this product as reported earlier by IP Pharma Doc Here and Here

Wednesday 25 March 2009

EU Patent litigation Harmonization: Unified patent litigation system (UPLS) on the cards

The European Commission has adopted a Recommendation to the Council that would provide the Commission with negotiating directives for the conclusion of an agreement creating a Unified Patent Litigation System (UPLS).
The commission recommended creation of integrated jurisdictional system for European patents and future community patents. The draft agreement would provide patentees with a more predictable, rapid and less expensive way to settle disputes in relation to their patents and is thereby expected to further growth, competitiveness. The creation of a single specialist court responsible for decisions on the European and the Community patent would increase legal certainty and promote a uniform application and interpretation of patent law at EU level and in the context of the EPC.
This constitutes a further significant step in the pursuit of the EU's patent reform agenda.

The present litigation system in Europe is quite expensive and full of uncertainties. Further, for IP professionals, to carry out infringement analysis and freedom to operate searches for EU market is quite challenging. The said recommendation if implemented would certainly help IP professionals.
Press release from commission Here

EU commission’s recommendation Here

Tuesday 24 March 2009

USFDA Approvals

Final Approvals
Cefazolin Sodium Injection:
Cephazone Pharma
Fluoxetine Capsules: Alembic Limited, Approval
Minocycline Hydrochloride Extended-Release Tablets: Barr Labs
Pantoprazole Sodium Delayed-Release Tablets: KUDCO Ireland Limited
Prednisolone Sodium Phosphate Oral Solution: Amneal Pharmaceuticals
Levetiracetam Tablets: Apotex
Zolpidem tartrate Tablets: Orexo AB
Apraclonidine Hydrochloride Ophthalmic Solution: Akorn
Omeprazole Delayed-Release Capsules: Dr. Reddy's
Indomethacin Extended-Release Capsules: Avanthi
Leuprolide Acetate Injection: Sun Pharma Global, Inc., Approval
Malathion Lotion: Synerx Pharma
Propranolol Hydochloride Extended-Release Capsules: Upsher-Smith
Ramipril Capsules: Ranbaxy
Glycopyrrolate Tablets:West-ward Pharmaceutical Corp
Methylprednisolone Acetate Injection: Sandoz
Quinapril Hydrochloride and Hydrochlorothiazide Tablets: Ranbaxy
Sertraline Hydrochloride Tablets: AustraPharma
Buspirone Hydrochloride Tablets: Dr. Reddy’s Lab
Citalopram Hydrobrobromide Tablets: Glenmark Generics
Nabumetone Tablets: Actavis Elizabeth
Temodar (Temozolomide) Injection: Schering Corp
Divalproex Sodium Extended-Release Tablets: Zydus Pharma., Mylan, Anchen Pharma (Taiwan)
Granisetron Hydrochloride Tablets: Dr. Reddy's Labs
Carboplatin I.V. Injection: Pharmachemie B.V.
Azelastine Hydrochloride Ophthalmic Solution: Apotex
Bupropion Hydrochloride Extended-Release Tablets: Watson Laboratories
Flumazenil Injection: Hikma Farmaceutica (Portugal)
Ibuprofen Capsules: Banner Pharmacaps
Risperidone Tablets: Cadista Pharmaceuticals
Sulfacetamide Sodium Lotion: Perrigo
Levetiracetam Tablets: Cipla
Stavudine Oral Solution: Cipla LtdLevalbuterol Inhalation Solution: Dey


Tentative Approval
Lopinavir and Ritonavir Tablets: Aurobindo Pharma and Matrix Labs
Lamivudine Tablets: Alkem Labs
Ketorolac Tromethamine Ophthalmic Solution: Alcon, Inc.
Rosiglitazone Maleate Tablets: Sandoz Inc.
Stavudine, Lamivudine and Nevirapine Tablets: Pharmacare Ltd.


(Source: USFDA)

Eszopiclone (Lunasta) 1 mg, 2 mg and 3 mg tablets: Innovator Sepracor Files Patent Infringement Lawsuit Against ANDA Filers

Innovator Sepracor announced (in a press release Here ) that it has filed a lawsuit in the U.S. District Court for the District of New Jersey against those companies who have filed abbreviated new drug applications (ANDAs) with Paragraph IV certifications for generic copies of Eszopiclone. Sepracor markets eszopiclone in the U.S. under the brand name LUNESTA®. The lawsuit alleges infringement of Sepracor’s following Orange Book listed patents for Eszopiclone 1 mg, 2 mg and 3 mg tablets:
US6,319,926 (Expiry: Jan 16, 2012): which covers a method for improving sleep quality or time comprising the step of administering an effective quantity of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-d ihydro-5H-pyrrolo[3,4-b]pyrazine, or a pharmaceutically acceptable salt thereof, in the form of its dextrorotatory isomer and essentially free of its levorotatory isomer, to a human.
US6,444,673 (Expiry: Jan 16, 2012): Which covers 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-d ihydro-5H-pyrrolo[3,4-b]pyrazine, or a pharmaceutically acceptable salt thereof, in the form of its dextrorotatory isomer and essentially free of its levorotatory isomer.
US6864257 (Expiry: Aug 30, 2012): Which covers method of inducing an effect selected from the group consisting of a hypnotic effect, a sedative effect and a tranquilizing effect, in a human in need of said induction, comprising administering to the human an effective quantity of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-d ihydro-5H-pyrrolo[3,4-b]pyrazine, or a pharmaceutically acceptable salt thereof, in the form of its dextrorotatory isomer and essentially free of its levorotatory isomer.
US7,381,724 (Expiry: Jan 16, 2012): Which covers mixture of isomers of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyl-oxy]-7-oxo-6,7- -dihydro-5H-pyrrolo[3,4-b]pyrazine, wherein the mixture has an optical rotation [.alpha.].sub.D.sup.20 of 135.degree..+-.3.degree. when measured at 1.0 g/100 mL in acetone.
Due to the commencement of this litigation, ANDA approval will be stayed until approximately June 15, 2012 (or potentially six months thereafter if Sepracor successfully obtains a pediatric exclusivity extension) or until a court decides that Sepracor’s patents are invalid, unenforceable or not infringed, whichever is earlier.
Should Sepracor successfully enforce its patents, ANDA approval should not occur until expiration of the applicable patents, one of which may be extended by Sepracor’s outstanding patent term extension application.
Innovator Sepracor got approval from USFDA to market Eszopiclone (Lunasta) 1 mg, 2 mg and 3 mg tablets on Dec 15, 2004.

Deptomycin for Injection (Cubicin) 500Mg/vial: Innovator sued Teva in Delaware district court

Innovator Cubist Pharma has filed a patent infringement lawsuit against Teva Parenteral Medicines (TPM) for alleged violation of Orange Book listed patents related to antibacterial formulation Daptomycin 500Mg/VIAL injectable IV infusion.
Following patents are listed for this producty in Orange Book:
US6468967 (Expiry: Sep 24, 2019): Which covers a method for administering daptomycin, comprising the step of administering to a human patient in need thereof a therapeutically effective amount of daptomycin in a dose of 3 to 75 mg/kg of daptomycin at a dosage interval that minimizes skeletal muscle toxicity, wherein the daptomycin dose is repeatedly administered at a dosage interval of once every 24 hours to once every 48 hours.
US6852689 (Expiry: Sep 24, 2019): Which covers a method for administering daptomycin, comprising the step of administering to a human patient in need thereof a therapeutically effective amount of daptomycin in a dose of at least 3 mg/kg of daptomycin at a dosage interval that minimizes skeletal muscle toxicity, wherein the daptomycin dose is repeatedly administered at a dosage interval of once every 48 hours to once weekly.
USRE39071 (Expiry: Jun 15, 2016): Which covers cyclic peptide derivatives (including Daptomycin) as product
Innovator has filed patent infringement suit in the U.S. District Court for the District of Delaware against Teva. As reported earlier by IP Pharma Doc Here, Teva sent it's Para IV notice letter to innovator in February, 2009. In it’s complaint, innovator has alleged infringement of ‘071 patent by Teva. Since, innovator has sued Teva within 45 days of Para IV notice receipt, there would be a 30 month stay on Teva's ANDA approval process.

Innovator got final approval from USFDA on Sep 12, 2003 to market this product

Risperidone (Risperdal) Oral Solution: US highest court refused to hear Apotex's writ of certiorari

The US highest court has refused to hear Apotex Inc.'s “writ of certiorari” regarding counterclaims of noninfringement in connection with a patent fight over Johnson & Johnson subsidiary Janssen's anti-psychotic drug Risperidone (Risperdal) Oral Solution 1 mg/ml. Following patents are listed for this product in Orange Book:
US4804663 (Expiry: Jun 29, 2008): Product
US5453425 (Expiry: Jan 11, 2015): Formulation
US5616587 (Expiry: Jan 11, 2015): Formulation
USRE39181 (Expiry: Jan 11, 2015): Formulation (reissue of ‘587 patent)
Teva has got 180 days exclusivity on this product. Apotex wants to get declaratory judgment on US5453425 and US5616587 from court. Innovator issued 'covenant not to sue' to Apotex for ‘425 and ‘587 patents. However, Apotex was not satisfied with this ‘convenent not to sue’, as it would have not triggered the Teva’s 180 days exclusivity. Apotex filed its declaratory judgment request in court, which rejected this request based on no article III controversy. In September, 2008, the CAFC upheld the district court’s decision (as reported earlier by IP pharm doc Here)and thwarted Apotex’s attempt to trigger 180 days exclusivity of Teva.

Monday 23 March 2009

Lanthanum Carbonate (Fosrenol) Chewable tablets 500 mg, 750 mg and 1gm: Innovator sued Mylan

Innovator Shire announced (in a press release Here) that it has filed a lawsuit in the U.S. District Court of the Southern District of New York against Mylan and Matrix Labs for infringement of Shire’s following Orange Book listed patents for Lanthanum Carbonate (Fosrenol) Chewable tablets 500mg, 750mg and 1gm:
US5968976 (Expiry: Oct 26, 2018): Which coves a pharmaceutical composition for the treatment of hyperphosphataemia comprising lanthanum carbonate
The lawsuit was filed in response to an Abbreviated New Drug Application filed by Mylan seeking USFDA approval to market and sell generic versions of Shire’s 500 mg, 750 mg, and 1 g FOSRENOL® (lanthanum carbonate) products.
Innovator has not asserted two other patents listed in Orange book like US7381428 and US7465465 which will expire on Aug 26, 2024).
Earlier, Ippharmadoc reported Here that innovator confirmed receipt of Paragraph IV notice letter from Barr and Mylan. Innovator has already sued Barr in District Court of the Southern District of New York as reported by us here.

Omega-3-acid Ethyl Esters (Lovaza) 1 g capsules: Pronova received Paragraph IV notice letter from Par

Innovator Pronova BioPharma announced (in a press release Here) that Pronova and its U.S. marketing partner GlaxoSmithKline have received a Paragraph IV Notice on March 17, 2009 from Par advising that Par has submitted an Abbreviated New Drug Application (ANDA) to the USFDA for approval to market a generic version of Omega-3-acid Ethyl Esters 1 g capsules (Lovaza).
Pa's notice letter states that its ANDA contains a Paragraph IV Certification alleging that the US5502077 (Expiry: Mar 26, 2013) and US5656667 (Expiry: Aug 27, 2018) patents are not valid, unenforceable, or will not be infringed by the commercial manufacture, use or sale of Par's product.
Also, Teva has filed ANDA with Paragraph IV certification against this product as reported earlier by IP Pharma Doc Here

Friday 20 March 2009

Desvenlafaxine (Pristiq): Impax in agreement with Wyeth for co-promotion of brand

Impax Labs announced (in a press release Here) that from July 1, 2009, Impax Pharma, the Company’s specialty brand products division will co-promote Wyeth’s Pristiq®. Impax Pharmaceuticals will utilize its 66 neurology-focused sales force to promote Pristiq® (Desvenlafaxine), a serotonin-norepinephrine reuptake inhibitor (SNRI) as a treatment for adult patients with major depressive disorder (MDD).
As previously announced, Impax Laboratories entered into a three-year co-promotion agreement with Wyeth in July 2008 to detail a product then to-be named by Wyeth for neurologists. Impax will receive a fee for each detail delivered. Other terms of this agreement are confidential and were not disclosed.
Desvenlafaxine succinate , which is chemically (4-[2-dimethylamino-1-(1-hydroxycyclohexyl) ethyl]phenol is Serotonin/Norepinephrine reuptake inhibitor (antidepressant). Desvenlafaxine succinate is an active metabolite of Venlafaxine (Effexor).

Dr. Reddy's Laboratories:Realigned Global Generics Dosage Form Strategy

Dr. Reddy's Laboratories announced (in a press release here) that it has realigned its Global Generics finished dosages strategy to focus on certain key geographies and would gradually exit some of the very small distributor driven markets.

The markets being exited would have an overall contribution of less than 1% to the topline. In addition to the US, India, Russia & CIS and Germany where the operations are already very large contributing to approx 90% (fig. for 9 months ended Dec 2008) of the Global Generics revenues, the company will continue operations in 10-15 markets wherein the company’s finished dosages sales are growing significantly.
This move represents an important new focus in the Global Generics business to consolidate and grow the Company’s presence in the key geographies where it already has a considerable presence. The exercise would result in reduction of complexity of operations on one hand and help in significantly enhanced customer service and market share on the other.(Source: Dr. Reddy’s press release)

Dr. Reddy’s Labs: Major gains in Russia/CIS region

Dr. Reddy’s Labs announced (in a press release Here) that it has crossed the milestone of $150 million of revenues in the Russia/CIS region for the fiscal year 2009. This milestone is a result of the efforts in building a branded franchise, cementing strong customer relationships and partnering with trade channels over last several years.
Dr. Reddy’s entered the Russia market in 1992 and consolidated its position during the turbulent currency crisis of the late 1990s. As per press release, Dr. Reddy’s is the largest Indian Pharmaceutical company in Russia and is also the fastest growing international branded generic company by volume.

Doxycycline Hyclate (Doryx) 150 mg DR tablets: Innovator sued Impax; ANDA approval delayed by 30 months

In our earlier post Here, we reported that Impax has provided notice to the New Drug Application (NDA) holders Warner Chilcott and Myne that it has submitted an Abbreviated New Drug Application (ANDA) for Doxycyline hyclate delayed-release tablets 150 mg, generic of Doryx(R), to the U.S. Food and Drug Administration (FDA). Impax's ANDA, contains a Paragraph IV certification stating that the Company believes its product does not infringe (is invalid or unenforceable) following Orange Book listed patent:
US6958161 (Expiry: Dec 15, 2022): Which covers a modified release preparation of Doxycycline
Warner Chilcott Limited announced (in press release Here) that one of its subsidiaries and Mayne Pharma have filed a second lawsuit against Impax Lab in the District Court for the District of New Jersey for infringement of Mayne's ‘161 patent.
Earlier, innovator Warner Chilcott announced (in a press release Here) that for 150 mg strength of Doryx there would be 30 month stay (as per USFDA's decision on citizen petition of innovator companies on 30 month stay provision, ANDA on 150 mg stregth was filed after patent listing on Dec, 2008) on ANDA approval process of Impax.
Importantly, there will be no 30 month stay on ANDA approval process of Impax for other strengths (75 and 100 mg).
Earlier post of Ippharmadoc on this product Here, Here and Here

Thursday 19 March 2009

Citizen petition on Minocycline, Doxycycline, Mycophenolate and Clindamycin: USFDA denied innovator’s petition on 30 month stay

On March 17, 2009 USFDA denied innovator’s like Medicis (on Minocycline), Warner chilcott (Doxycycline) and Roche’s (Mycophenolate and Clindamycin) citizen petition against ANDA’s which contains a Paragraph IV certification to a patent listed in the Orange Book under the transition rules of § 4(b)(1) of the QI Program Supplemental Funding Act of 2008.
Innovator requested in the citizen petitions that USFDA should interpret the QI Act , wherein, patents listed pursuant to QI Act § 4(b)(1) should be treated as having been filed with the original NDA, thus providing for 30-month stay on ANDA approval process of generic companies who had filed ANDA on old antibiotic products before implementation of Q1 programme

Orange Book blog Here

FDA law blog Here

Minocycline HCl (Solodyn) 45, 90 and 135 mg ER tablets: Innovator Medicis settled with Teva; generic launch expected in 2011

Innovator Medicis and Teva Pharma announced (in press release here) that they have agreed to terminate all legal disputes between them relating to SOLODYN(R) (Minocycline HCl, USP) Extended Release Tablets. Pursuant to an agreement entered into between the parties, Teva has confirmed that Medicis' patents relating to SOLODYN(R) are valid and enforceable, and cover Teva's activities relating to its generic product under Abbreviated New Drug Application (ANDA) #65-485.

Following patents was listed in Orange Book for this product (on Dec 5, 2008 as per § 4(b)(1) of the QI Program Supplemental Funding Act of 2008 for old antibiotic products):
US5908838 (Expiry: Feb 19, 2018): which covers method for reducing the incidence or severity of vestibular side effects resulting from the treatment of acne by the use of oral tetracycline antibiotics, comprising administering the oral tetracycline antibiotic (including Minocycline hydrochloride) in a slowly dissolving dosage form (patent covers primary indication).
Various generic players like Impax, Matrix, Sandoz and Barr have amended their ANDA (after patent listing as per Q1 programme for old antibiotic products patent listing in Orange Book) and filed Para IV against said patent, subsequently, innovator sued these generic players in Delaware district court (as reported earlier by IPPharmadoc Here, Here, here).

Eralier, Teva announced in a press release (Link to news Here) about final approval from USFDA on this product and shipment of this product in US market.
As part of the settlement, Teva has agreed to immediately stop all further shipments of generic SOLODYN(R). Medicis has agreed to release Teva from liability arising from any prior sales of its generic SOLODYN(R), which were not authorized by Medicis.
Under the terms of the Settlement Agreement, Teva has the option to market its generic versions of SOLODYN(R) 45mg, 90mg and 135mg under the SOLODYN(R) intellectual property rights belonging to Medicis commencing in November 2011, or earlier under certain conditions. Additional terms were not disclosed.

The innovator got final approval to market this product for 45, 90 and 135 mg strengths on May 8, 2006.
Annual sales of this product were approximately $365 million in the United States for the twelve months that ended January 31, 2009, based on IMS sales data

Wednesday 18 March 2009

Atorvastatin hemicalcium (Lipitor): Innovator got product patent reissued as USRE40667

Pfizer Inc announced today (in a press release Here) that the U.S. Patent & Trademark Office (USPTO) has granted reissue patent USRE40667 (Link), relating to Atorvastatin hemicalcium (Lipitor).

The company had applied for the reissue patent in January 2007, in order to correct a technical defect in the US5273995 enantiomer patent for atorvastatin calcium, the salt form of atorvastatin sold as Lipitor. On January 6, 2009, the company announced that the USPTO had issued a “Notice of Allowance” accepting the company’s application to correct the technical defect in the ‘995 patent as reported earlier by this blog Here.

The reissue patent will have the same force and effect as the original ‘995 patent and the same June 2011 expiration date (including the six-month pediatric exclusivity period).

Earlier, the patent was invalidated by CAFC in August, 2006 (Particularly claim 6 of this patent due to wrong dependency on claim 2 as per 35 USC 112) during litigation of innovator with Ranbaxy. This patent is a strong barrier for other generic players market entry. Also, innovator has sued generic players like Teva, Apotex and Cobalt for this patent.Earlier news of IPPharmadoc on this product here, and Here

DOXYCYCLINE HYCLATE (DORYX) 150 mg DR tablets: Impax Confirms ANDA Filing

Impax Labs today confirms (in a press release Here) that it has provided notice to the patent and New Drug Application (NDA) holders that it has submitted an Abbreviated New Drug Application (ANDA) for doxycyline hyclate delayed-release tablets 150 mg, generic of Doryx(R), to the U.S. Food and Drug Administration (FDA). Impax's ANDA, contains a Paragraph IV certification stating that the Company believes its product does not infringe (is invalid or unenforceable) following Orange Book listed patent:
US6958161 (Expiry: Dec 15, 2022): Which covers a modified release preparation having one or more coated core elements, each core element comprising an active ingredient selected from the group consisting of the acid salts of Doxycycline, Tetracycline, Oxytetracycline, Minocycline, Chlortetracycline or Demeclocycline and having a modified release coating, wherein a stabilising coat is provided between each core element and its modified release coating so that, upon in vitro dissolution testing, the amount of active ingredient released at any time on a post-storage dissolution profile is within 40 percentage points of the amount of active ingredient released at any time on a pre-storage dissolution profileDOXYCYCLINE HYCLATE (DORYX), which the Innovator markets and sells in 150, 100 and 75 mg strengths in the United States under a license agreement with Hospira's subsidiary, Mayne Pharma, is a tetracycline-class oral antibiotic, which is primarily indicated for rickettsial infections, sexually transmitted infections, respiratory tract infections, specific bacterial infections, ophthalmic infections, anthrax, including inhalational anthrax (post-exposure), alternative treatment for selected infections when penicillin is contraindicated, adjunctive therapy in acute intestinal amebiasis and severe acne, and prophylaxis of malaria.
The '161 Patent has been listed in the FDA's Orange Book pursuant to the transition provisions of the QI Program Supplemental Funding Act of 2008 enacted October 8, 2008 (Wherein, antibiotic product approved before November, 1997 will have Orange Book listing).
Eralier, Impax and other generic players like Mutual Pharma, Mylan Pharma, Actavis and Sandoz has challenged innovator by filing ANDA on 100 and 75 mg strength, subsequently, innovator has sued all generic players for the infringement of ‘161 patent in District of New Jersey as reported earlier by this blog Here and Here
According to Wolters Kluwer Health, U.S. sales of Doryx(R) 150 mg were approximately $29 million in the 12 months ended January 2009.

Update

Innovator Warner Chilcott announced in a press release that for 150 mg stregth of Doryx there would be 30 month stay (as per USFDA's decision on citizen petition of innovator companies on 30 month stay provision, ANDA on 150 mg stregth was filed after patent listing on Dec, 2008) on ANDA approval process of Impax.

Importantly, there will be no 30 month stay on ANDA approval process of Impax for other stregths (Link to news Here)

Clindamycin Phosphate Aerosol Foam 1%(Evoclin): Perrigo and Partner Cobrek filed Para IV; innovator sued Coberk

Perrigo Company today announced (in a press release Here) that its partner Cobrek Pharma has filed an Abbreviated New Drug Application (ANDA) for Clindamycin Phosphate Aerosol Foam 1%, a generic version of Evoclin(R) Foam 1%. The Company believes that Cobrek is the first to file an ANDA with a Paragraph IV certification against Evoclin(R).
The ANDA for Clindamycin Phosphate Foam, 1%, which was filed prior to enactment of the Q1 Program Supplemental Funding Act of 2008 (the "Q1 Act"), was timely amended to contain a Paragraph IV Certification in accordance with the Q1 Act. Innovator STIEFEL LABS INC has listed following patents in Orange Book:
US7141237 (Expiry: Jan 23, 2024): Which covers a topical delivery composition in a pressurized container, said composition comprising: up to 15% w/w of clindamycin phosphate; from about 83% to about 97.9% w/w of a quick-breaking foaming agent, wherein said quick-breaking foaming agent comprises a C1-C6 alcohol, a C14-C22 alcohol, water, and a surfactant; and from about 2% to about 7% w/w of an aerosol propellant selected from the group consisting of a hydrocarbon, a chlorofluorocarbon, dimethyl ether, hydrofluorocarbons and a mixture thereof, a base; and wherein said composition is a quick-breaking temperature sensitive foam after release from said container.
US7374747 (Expiry: Aug 9, 2026): A method for treating a bacteria-mediated disease, said method comprising: applying a quick-breaking temperature sensitive foam composition to the skin of a subject in need thereof, said composition comprising: up to 15% w/w of clindamycin phosphate; from about 83% to about 97.9% w/w of a quick-breaking foaming agent, wherein said quick-breaking foaming agent comprises a C1-C6 alcohol, a C14-C22 alcohol, water, and a surfactant; from about 2% to about 7% w/w of an aerosol propellant selected from the group consisting of a hydrocarbon, a chlorofluorocarbon, dimethyl ether, hydrofluorocarbons and a mixture thereof; and a base, to treat said bacteria-mediated disease.
On March 13, 2009, Stiefel filed suit alleging patent infringement in the United States District Court for the District of Delaware against Perrigo and its partner Cobrek. Stiefel also has filed a Citizen Petition with the U.S. Food and Drug Administration seeking to have a 30 month stay of Cobrek's ANDA approval imposed. The FDA has not ruled, neither have the courts, regarding whether the Q1 Act entitles Stiefel to a 30 month stay.
Evoclin(R) (clindamycin phosphate) Foam 1% is a topical antibiotic indicated for topical application in the treatment of acne vulgaris, and contains clindamycin phosphate,USP, at a concentration equivalent to 10 mg clindamycin per gram in a hydroethanolic foam vehicle consisting of cetyl alcohol, ethanol, polysorbate 60, potassium hydroxide, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant.Evoclin had sales of approximately $44 million for the 12 months ended January 2009, as measured by Wolters Kluwer Health.

Sevelamer hydrochloride (Renagel) 400 and 800 mg tablets: Innovator Genzyme sued Impax

Generic player Impax Lab confirms (in a press release Here) that it has initiated a challenge of the patents listed by Genzyme Corporation in connection with its RENAGEL® (Sevelamer hydrochloride) tablets, 400 mg and 800 mg.
Impax filed its Abbreviated New Drug Application (ANDA) containing a paragraph IV certification for a generic version of RENAGEL® with the U.S. Food & Drug Administration (FDA). Following receipt of the notice from the FDA that Impax's ANDA had been accepted for filing, Impax notified the New Drug Application holder and patent owner of its paragraph IV certification.
Following patents are listed in Orange Book for this product:

US5496545 (Expiry: Aug 11, 2013): The patent covers formulation and method of use

US5667775 (Expiry: Sep 16, 2014) : The patent covers a method for removing phosphate from a patient by ion exchange comprising orally administering to said patient a therapeutically effective amount of a composition comprising Sevelamer
US6509013 (Expiry: Aug 11, 2013): The patent covers a pharmaceutical composition consisting essentially of a carrier and at least one water insoluble, crosslinked polymer
US7014846 (Expiry: Aug 11, 2013): The patent covers a pharmaceutical composition comprising a carrier and a crosslinked, water insoluble polyallylamine homopolymer, wherein said polyallylamine homopolymer comprises repeat units wherein said polyallylamine homopolymer is crosslinked with an epichlorohydrin crosslinking agent, and wherein the homopolymer is fully protonated, partially protonated or unprotonated.

US6733780 (Expiry: Oct 18, 2020): The patent covers a tablet comprising a core and a coating thereof, wherein at least about 95% by weight of the core is an aliphatic amine polymer selected from the group consisting of unsubstituted and N-substituted poly(allylamine), poly(diallylamine), and poly(vinylamine).

US7459151 (Expiry: Aug 11, 2013): The patent covers a method for removing phosphate from a patient in need thereof comprising orally administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising a crosslinked, water insoluble polyallylamine copolymer wherein said crosslinked, water insoluble polyallylamine copolymer consists of a crosslinking agent
Innovator Genzyme has sued Impax On March 13, 2009 for the infringement of '545, '775, '013 and '846 in United States District Court for the District of Maryland.
Also, innovator has sued Lupin for the infringement of '545, '775, '013 and '846 in Delaware District Court as reported earlier by IPPharmadoc Here.
Sevelamer (Renegal) is a phosphate binder indicated for the control of serum phosphorus in patients with chronic kidney disease on dialysis.

According to Wolters Kluwer Health, U.S. sales of RENAGEL® were approximately $469 million across both strengths for the period ending January 2009.

Tuesday 17 March 2009

Lanthanum Carbonate (Fosrenol) Chewable tablets 500 mg, 750 mg and 1gm: Innovator sued Barr

Innovator Shire announced (in a press release Here ) that it has filed a lawsuit in the U.S. District Court of the Southern District of New York against Barr Labs for infringement of following Orange Book listed patents for Lanthanum Carbonate (Fosrenol) Chewable tablets 500mg, 750mg and 1gm:

US5968976 (Expiry: Oct 26, 2018): Which coves a pharmaceutical composition for the treatment of hyperphosphataemia comprising lanthanum carbonate

US7381428 (Expiry: Aug 26, 2024): Which coves a stabilized Lanthanum Carbonate Compositions against substantial decarboxylation to lanthanum hydroxycarbonate before administration by admixing the lanthanum carbonate in an amount of from 13.4-13.9% to 32.2-33.3% by weight of the composition as elemental lanthanum with a monosaccharide or disaccharide in an amount from 20 to 80% by weight of the composition, wherein the monosaccharide or disaccharide is dextrates, mannitol, sorbitol, or a mixture thereof and the amount of the monosaccharide or disaccharide is such that lanthanum hydroxycarbonate is not observed in an x-ray powder diffraction (XRPD) pattern of the lanthanum carbonate composition after it has been exposed to 60 degree C and 95% relative humidity for at least 7 days.

US7465465 (Expiry: Aug 26, 2024): Which coves a lanthanum carbonate pharmaceutical formulation in a chewable tablet, comprising lanthanum carbonate in an amount of from about 200 mg to about 1000 mg elemental lanthanum in the proportion of about 10 to about 40 wt % of the formulation as elemental lanthanum and pharmaceutically acceptable excipients comprising a diluent in an amount from about 40 to about 80 wt % of the formulation and a flow agent in an amount from about 0.1 to about 5.0 wt % of the formulation, produced by a process which comprises the steps of: a. blending the lanthanum carbonate and the pharmaceutically acceptable excipients to form a mixture; or b. blending the lanthanum carbonate and the pharmaceutically acceptable excipients, compressing the resulting combination into a slug material or roller compacting the resulting combination into a strand material, and milling the prepared material into a free flowing mixture; and c. compressing the mixture formed in steps a or b into a tablet, wherein the process is performed without wet granulation or drying, the diluent is dextrates, corn syrup, oligosaccharide, isomaltooligosaccharide, glucose, lycasin, xylitol, lactitol, erythritol, mannitol, isomaltose, polydextrose, dextrin, starch, fructose, xylitol, maltodextrin, maltitol, isomalt, lactose, sorbitol, microcrystalline cellulose, sucrose based diluent-binders, confectioner's sugar, calcium sulfate dihydrate, calcium lactate trihydrate, hydrolysed starches, dextrose, inositol, hydrolyzed cereal solids, amylase, or glycine, and the flow agent is magnesium stearate, talc, polyethylene glycol, silica, colloidal anhydrous silica, hydrogenated vegetable oils, glyceryl behenate, or glyceryl monostearate.

The lawsuit was filed in response to an ANDA (Abbreviated New Drug Applications) filed by Barr seeking USFDA approval to market and sell generic versions of Shire’s 500 mg, 750 mg, and 1 g FOSRENOL® (Lanthanum Carbonate) products.Under the Hatch-Waxman Act, because Shire filed its patent infringement lawsuit within 45 days of receiving Barr’s Paragraph IV notification letter, the FDA must refrain from approving Barr's ANDA for 30 months, or until a district court decision finding that the patents are invalid or not infringed, whichever occurs earlier. The stay on generic approval will expire on April 26, 2012 unless terminated earlier.Shire is confident in its intellectual property portfolio protecting FOSRENOL®, and will enforce its patents against infringers to the fullest extent allowed by law.

Innovator got approval for Lanthanum carbonate (Fosrenol) Chewable tablets 500mg on Oct 26, 2004, while, 750mg and 1gm were approved by USFDA on Nov 23, 2005

Earlier, Ippharmadoc reported Here that innovator confirmed receipt of Paragraph IV notice letter from Barr and Mylan.

Monday 16 March 2009

Omega-3-acid Ethyl Esters (Lovaza) 1 g capsules: Pronova received Paragraph IV notice letter from Teva

Innovator Pronova BioPharma announced (in a press release Here) that Pronova and its U.S. marketing partner GlaxoSmithKline have received a Paragraph IV Notice Letter dated March 9 2009 from Teva advising that Teva has submitted an Abbreviated New Drug Application (ANDA) to the US Food and Drug Administration for approval to market a generic version of Omega-3-acid Ethyl Esters 1 g capsules (Lovaza).
Following patents are listed in Orange Book for Omega-3-acid Ethyl Esters (Lovaza) 1 g capsules:
US5502077 (Expiry: Mar 26, 2013): Which covers a method for the treatment or prophylaxis of hypertriglyceridemia in a human patient, which comprises orally administering to the patient a pharmaceutical composition in which the active ingredients consist essentially of a mixture of fatty acids of which at least 80% by weight is comprised of a combination of (all-Z omega-3)-5,8,11,14,17-eicosapentaenoic acid (EPA) and (all-Z omega-3)-4,7,10,13,16,19-docosahexaenoic acid (DHA) in a weight ratio of EPA:DHA of from 1:2 to 2:1, said composition being administered in amounts providing a daily dosage of 1 to 10 grams of said mixture of fatty acids
US5656667 (Expiry: Aug 27, 2018): Which covers a method for elevating the HDL cholesterol level in the serum of a human patient, which comprises administering to the patient a pharmaceutical composition in which the active ingredients consist essentially of a mixture of fatty acids of which at least 80% by weight is comprised of a combination of (all-Z omega-3)-5,8,11,14,17-eicosapentaenoic acid (EPA) and (all-Z omega-3)-4,7,10,13,16,19-docosahexaenoic acid (DHA) in a weight ratio of EPA:DHA of from 1:2 to 2:1, said composition being administered in amounts providing a daily dosage of 1 to 10 grams of said mixture of fatty acids.
US5698594 (Expiry: Aug 4, 2009): Which covers a method for the treatment or prophylaxis of hypertension in an adult human patient, which comprises administering to the patient, on a daily basis, an effective amount of a pharmaceutical composition in which the active ingredients consist essentially of a mixture of fatty acids of which at least 80% by weight is comprised of a combination of (all-Z omega-3)-5,8,11,14,17-eicosapentaenoic acid (EPA) and (all-Z omega-3)-4,7,10,13,16,19-docosahexaenoic acid (DHA) in a weight ratio of EPA:DHA of from 1:2 to 2:1 and of which at least 1% by weight of the mixture of fatty acids is comprised of (all-Z omega-3)-6,9,12,15,18-heneicosapentaenoic acid.
Teva's notice letter states that its ANDA contains a Paragraph IV Certification alleging that the '077 and '667 patents are not valid, unenforceable, or will not be infringed by the commercial manufacture, use or sale of Teva's product.
As per press release, innovator Pronova has full confidence in its intellectual property portfolio protecting Lovaza(TM) and will vigorously defend and enforce its patents.
LOVAZA (Omega-3-acid ethyl esters) is indicated as an adjunct to diet to reduce very high (≥500 mg/dL) triglyceride (TG) levels in adult patients, the approved formulation also contains fish oils. USFDA approved omega-3-acid ethyl esters (Lovaza) on Nov 10, 2004.

Lopinavir+Ritonavir, 200 mg/50 mg Tablets: Matrix got tentative approval under PEPFAR

Mylan Inc. today announced (announced in a press release Here) that Matrix Laboratories Limited, its India-based subsidiary in which it holds a 71.5% controlling interest, has received the first and only tentative approval from the U.S. Food and Drug Administration (FDA) under the President's Emergency Plan for AIDS Relief (PEPFAR) for its Abbreviated New Drug Application (ANDA) for Lopinavir+Ritonavir Tablets, 200 mg/50 mg. Matrix's version of this product is heat-stable and affordable, making it practical for distribution and use in warm climates.

Thursday 12 March 2009

Biogeneric/biosimilar: Bill H.R. 1427 introduced

A group of lawmakers like Henry A. Waxman, Frank Pallone, Nathan Deal, and Jo Ann Emerson introduced H.R. 1427, the “Promoting Innovation and Access to Life-Saving Medicine Act,” a bipartisan bill to allow the United States Food and Drug Administration (USFDA) to approve affordable copies of biotech drugs. Biotech drugs, while often life-saving, are the fastest growing and most expensive components of the US’s prescription drug bill. Many of them cost tens of thousands of dollars a year — prices that put them out of reach of patients and impose an unsustainable burden on employers, insurers, and the federal government.
Link to press release Here
Link to proposed bill Here
Link to important highlights of bill Here

Levalbuterol HCl Inhalation Solution(1.25 mg/3 mL, 0.63 mg/3 mL and 0.31 mg/3 mL) :Innovator settled with Barr and Teva

Innovator Sepracor announced (in a press release Here) that it has entered into a Settlement and License Agreement with Teva Pharma and Barr Labs to resolve the patent litigation against Barr involving Sepracor’s XOPENEX® brand Levalbuterol HCl Inhalation Solution products (1.25 mg/3 mL, 0.63 mg/3 mL and 0.31 mg/3 mL) and to grant a license to Barr and Teva.
The agreement permits Barr and Teva to launch generic versions of these XOPENEX Inhalation Solution dosages under terms of a non-exclusive license commencing on February 17, 2013. The agreement also contains provisions whereby the effective date of Barr’s and Teva’s license can be earlier under certain circumstances. Upon launch, Teva and Barr will pay Sepracor a royalty on their respective profit margins generated from the sales of generic versions of these XOPENEX Inhalation Solution dosages. The parties agreed to promptly file a consent final judgment and dismissal in the United States District Court for the District of Delaware that will conclude this litigation.

Memantine hydrochloride (Namenda): USPTO Issues Notice of Final Determination for Patent Term Extension, Generic Launch Delayed

Innovator Forest Lab and Merz Pharma announced (in a press release here) that the U.S. Patent and Trademark Office has issued a Notice of Final Determination granting the full five years of patent term extension for US5,061,703 (the '703 Patent), which is listed in the U.S. Food and Drug Administration Orange Book for NAMENDA(R) (Memantine hydrochloride). The said patent covers a method for the prevention or treatment of cerebral ischemia comprising the step of administering, to a patient in need thereof, an effective amount of Memantine.
Forest has an exclusive license to the '703 patent from the German pharmaceutical company Merz Pharma. Forest and Merz have commenced patent litigation against several generic manufacturers ( as reported by us Here, Here and Here) who have filed ANDAs seeking FDA approval to market generic versions of NAMENDA. A trial in this litigation, pending in the U. S. District Court for the District of Delaware, is scheduled for April 2010. After review of the regulatory timeline for approval of NAMENDA(R) the U.S. Patent and Trademark Office determined that the '703 Patent is entitled to the full five years of patent term extension and will expire on April 11, 2015 (instead of as originally anticipated on September 13, 2013), accordingly, generic launch will be delayed.
The earlier Orange Book expiry for this product was April, 2010. Now, generic launch would be delayed for 5 years.

Monday 9 March 2009

Montelukast Tablets (Singulair): Law firm requested patent re-examination of compound patent

A firm that specializes in challenging the validity of patents has requested the USPTO to re-examine innovator Merck’s Orange Book listed patent US5565473 for Montelukast Tablets (Singulair) . Independent firm Article One Partners LLC said its online community found two pieces of evidence that suggest the asthma and allergy drug's key ingredient isn't novel. Merck is trying to prevent Teva from making a generic version of the product before its patent expires in 2012. Last week, in an opening statement for the federal trial, Merck's attorney maintained the U.S. patent is valid and enforceable (as reported by CNN Here)
Teva is first para IV filer for Montelukast tablets 4 and 5 and 10 mg/tablet. Teva filed its ANDA with para IV certification on December, 2006 against following Orange Book listed patent:

US5565473 (Expiry: 8/3/2012): which covers unsaturated hydroxyalkylquinoline acids as leukotriene antagonists, including Montelukast as product.

Innovator sued Teva on April, 2007 for the infringement of '473 patent. The case is ongoing at New Jersey District Court (Discovery phase).Now, Teva has came up with strong invalidation grounds against said patent with allegation of intent to deceive USPTO against innovator, during prosecution of '473 patent
Teva has requested court that Merck withheld two important prior art documents authored by Merck's scientist Dr Robert Young during prosecution of said patent. The hearing for this case is scheduled in October, 2008.

If Teva succeed in its attempt, then generic space will open early for this product in US market

Sevelamer hydrochloride (Renagel) 400 and 800 mg tablets: Genzyme sued Lupin

Innovator Genzyme had sued Indian generc players Lupin for allegedly filing ANDA with Paragraph IV certification as part of Lupin's generic version of Genzyme's Sevelamer hydrochloride (Renagel) 400 and 800 mg tablets.
Following patents are listed in Orange Book for this product:
US5496545 (Expiry: Aug 11, 2013): The patent covers formulation and method of use
US5667775 (Expiry: Sep 16, 2014) : The patent covers a method for removing phosphate from a patient by ion exchange comprising orally administering to said patient a therapeutically effective amount of a composition comprising Sevelamer
US6509013 (Expiry: Aug 11, 2013): The patent covers a pharmaceutical composition consisting essentially of a carrier and at least one water insoluble, crosslinked polymer
US7014846 (Expiry: Aug 11, 2013) : The patent covers a pharmaceutical composition comprising a carrier and a crosslinked, water insoluble polyallylamine homopolymer, wherein said polyallylamine homopolymer comprises repeat units wherein said polyallylamine homopolymer is crosslinked with an epichlorohydrin crosslinking agent, and wherein the homopolymer is fully protonated, partially protonated or unprotonated.
US6733780 (Expiry: Oct 18, 2020): The patent covers a tablet comprising a core and a coating thereof, wherein at least about 95% by weight of the core is an aliphatic amine polymer selected from the group consisting of unsubstituted and N-substituted poly(allylamine), poly(diallylamine), and poly(vinylamine).
US7459151 (Expiry: Aug 11, 2013): The patent covers a method for removing phosphate from a patient in need thereof comprising orally administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising a crosslinked, water insoluble polyallylamine copolymer wherein said crosslinked, water insoluble polyallylamine copolymer consists of a crosslinking agent
innovator has sued Lupin for the infringement of '545, '775, '013 and '846 in Delaware District Court.
Earlier, Lupin sent its Para IV letter to innovator on January 20, accordingly, innovator sued lupin within 45 days to delay Lupin's ANDA approval for 30 months.
Sevelamer was first disclosed in USSR patent 417441 (patent by Tashkent Polytechnic University), accordingly, there is no product patent for this compound. Further, to thwart generic challenge innovator has listed patents covering method of use and formulation in Orange Book.
Genzyme had sales last year of $678 million for Renagel and a companion drug, Renvela, the company said last month. Renegal is used for the control of serum phosphorus in patients with chronic renal failure and on dialysis. Genzyme reported $4.6 billion in total revenue for 2008.

Friday 6 March 2009

Quinapril Hydrochloride + Hydrochlorothiazide (Accuretic): Ranbaxy got final approval, product to be developed in Ohm Lab

After recent letter from USFDA, wherein, FDA invoked Application Integrity Policy (AIP) against Ranbaxy's Paonta Sahib facility as reported by us here, now, there is a good news for Ranbaxy. Ranbaxy has started getting more approvals from there US based manufacturing facility OHM Laboratories .

Ranbaxy announced Here that the company has received an approval from the U.S. Food and Drug Administration for its Abbreviated New Drug Application for Quinapril Hydrochloride + Hydrochlorothiazide (Quinapril + HCTZ) Tablets, 10mg/12.5mg, 20mg/12.5mg and 20mg/25mg.

The Application for the drug was submitted by Ranbaxy, from its OHM Laboratories manufacturing facility, at New Jersey, USA. The Office of Generic Drugs, USFDA, had determined the Ranbaxy formulations to be bioequivalent and as having the same therapeutic effect as that of the reference listed drug, Accuretic Tablets of Pfizer Pharmaceuticals Ltd.This is the second ANDA approval granted by the USFDA, to Ranbaxy, in the last two months. Quinapril + HCTZ, is an ACE inhibitor and is used to treat high blood pressure.Ohm, based in North Brunswick, New Jersey, USA, is a wholly owned subsidiary of Ranbaxy Laboratories Limited. Ohm is engaged in the sale and distribution of generic and branded private label, OTC products in the U.S. healthcare system.

Thursday 5 March 2009

Levocetirizine (Xyzal): Synthon announced EU approval

Synthon announced today that it has successfully concluded its registration procedures for Levocetirizine. Regulatory clearance has been obtained for Synthon's product in around fourteen European countries using decentralized procedures (DCP). Registration has been established for 5 mg filmcoated tablets. Synthon's product is a fully bioequivalent version of the oral anti-histamine drug Xyzal®. The product contains the active ingredient levocetirizine, which is the enantiopure form of cetirizine, the active ingredient in UCB’s product Zyrtec®.
(Source pharmalive Here)

New Paragraph IV filings reported by USFDA till March, 2009

Brimonidine Tartrate and Timolol Maleate 0.2%/0.5% Ophthalmic Solution (Combigan) Para IV filed on Nov 21, 2008

Capecitabine 150 mg and 500 mg Tablets (Xeloda). Para IV filed on Nov 10, 2008

Diclofenac Sodium and Misoprostol 75 mg/0.2 mg Delayed-release Tablets (Arthrotec) Para IV filed on Nov 28, 2008

Guaifenesin and Dextromethorphan 600 mg/30 mg and 1200 mg/60 mg Extended-release Tablets (Mucinex DM) Para IV filed on Dec 17, 2008

Lovastatin and Niacin 20 mg/750 mg Extended-release Tablets (Advicor) Para IV filed on Dec 17, 2008
Sevelamer Carbonate 800 mg tablets (Renvela) Renvela Para IV filed on Dec 4, 2008

(Source: USFDA)

Tuesday 3 March 2009

Innovator in generic business: Pfizer announced licensing agreement with Aurbindo pharma to expand generic portfolio

Pfizer has agreed to license generic solid oral dosage forms and injectable medicines from India's Aurobindo Pharma Ltd to commercialize medicines that are no longer patent protected and have lost market exclusivity in the regulated market .

In the deal announced on Tuesday, Pfizer said it expected the products acquired to deliver more than $200 million in near future, according to David Simmons, general manager of Pfizer's established products business unit.
The products expand Pfizer's growing generics portfolio and are versions of drugs originally made by companies other than Pfizer. Financial terms of the deal were not disclosed.
Pfizer's Greenstone subsidiary already sells above 300 Pfizer medicines that have lost patent protection but still brought in a combined $10 billion last year. As per press release, Pfizer expects major revenue from generic business in 2013.

The licensing agreement with Aurbindo for generics can be attributed to patent expiry of blockbuster formulation of Pfizer like Atorvastatin, Sildenafil citrate, Celecoxcib, Pregabalin and Voriconazole etc. in near future. Pfizer is focusing on off-patent medicines as one avenue to spur profits as the drugmaker encounters generic competition that threatens revenue of its own top sellers.

Eralier, Pfizer acquired some major innovator companies like Warner-Lambert / Parke-Davis / Agouron, Pharmacia / Upjohn / Searle, SUGEN. Recently, Pfizer acquired Wyeth and Bayer to further strengthen its innovation approach.

Innovator companies are nowadays switching over to generic business after patent expiry of their blockbuster drugs. The trend was started by Novartis which opened it’s successful generic unit Sandoz, later on other innovator companies like Daiichi (Ranbaxy), Sanofi Aventis (Zentiva) entered into generic business.

Following are some factors for innovator companies interest in generic business:

1) Loss of innovation: Drug development is a very risky affair which can consume billion dollars. All the latest techniques of drug development have not led to a blockbuster drugs. In nutshell, the innovation pipeline has dried up. Although, research is going on but these companies know that its difficult to launch a drug in 2-5 yr time, to cover up that gap and fund research generic buissness is ideal choice

2) Off-patent Scenario: After the expiry of key patent of innovator, its difficult to sustain in competion with generic players. The market for innovator product after generic launch erode very quickly.

3) High cost of drug development: With drug intermediate and other raw material prices zooming, the new drug development has became more expensive. Further, clainical trials ae also becoming more expensive.

4) Thriving generic companies: Some of the generic companies have achieved sales equivalent to innovator. The innovator mostly get 5 yr exclusivity and sales normally rises yearwise. By the end of 4th year of exclusivity, generic companies are ready with their strategy and file dossier to challenge innovator. As in US First para IV filer got 180 days exclusivity, so if a generic player enter after the end of innovator's 5 yr exclusivity they got profit in the tune of millions (Some times sales achieved by innovator in first 3 years of exclusivity). Further, the risk and money involved for generic companies for development and launch is minimal.

5) Pro generic patent laws: The patent laws in US and EU are becoming more favorable to generic companies. The KSR V.s Teleflex decision which changed the obviousness concept is proving detrimental to product patents in US. Recent example for this are Pramipexole and Ramipril, whose product patent was invalidated by Us court. Recently, in Europe the product patent of Esomeprazole got invalidated.
6) Failure on Patent evergreening: Generic companies in the last 8 years have devloped their skills to stop patent evergreening attempts of innovator. Earlier, innovator in an attempt of evergreening of patent would get patents on polymorph, salt, formulation, purity, hausner ratio, bulk density, method of use, new combination etc. to thwart generic challenge. But all these patent are not sufficient to stop generic challenge once molecule or product patent expires.


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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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