Mylan vs Astrazeneca: IPR2015-01340

Mylan filed an IPR against US RE44,186 which is a reissue of US 6,395,767. US ‘767 originally issued to Bristol-Myers Squibb Company. US ‘186 claims Saxagliptin and listed in Orange Book.

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Before filing an IPR mylan was sued by Astrazeneca for the patent infringement of U.S. Patent Nos. 7,951,400, RE44,186 and 8,628,799. The cause of action was triggered when Mylan filed two Abbreviated New Drug Applications (“ANDA”) Nos. 205980 and 205981 with the U.S. Food and Drug Administration (“FDA”) for approval to market Saxaglitptin HCl tablets-generic versions of AstraZeneca’s ONGLYZA ® drug product-and Saxaglitptin HCl and Metformin HCl extended-release tablets-generic versions of AstraZeneca’s KOMBIGLYZE™ XR drug product-prior to expiration of the ‘400 Patent, the ‘186 Patent, and the ‘799 Patent.

Mylan filed a motion (Civil Action No. 14-696-GMS) to dismiss the above suit for lack of personal jurisdiction pursuant to Federal Rule of Civil Procedure 12(b)(2). Further, on Nov 05, 2014 the court denied Mylan’s motion to dismiss for lack of personal jurisdiction.

Saxagliptin:

Saxagliptin is a dipeptidyl peptidase-4 inhibitor. Saxagliptin is developed by Bristol-Myers Squibb (BMS-477118), in 2007 AstraZeneca joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug. Saxagliptin was approved by FDA on Jul 31, 2009, which is marketed under the brand name ONGLYZA. Further, Astrazeneca also received FDA approval to Metformin HCl; Saxagliptin HCl which is marketed under the brand name KOMBIGLYZE XR. Currently there are two patents (US ‘400 and US ‘186) listed in OB for Saxagliptin.

IPR2015-01340:

Mylan brought this challenge against US RE44,186 (reissue of  US ‘767) on the grounds of obviousness over the disclosures of Bio-organic & Medicinal Chemistry Letters, Vol. 6, No. 10, pp. 1163-1166, 1996, WO 1998/19998, Biochemistry 1991, 30, 2674-2684 and Angew. Chem. Int. Ed. Engl. 1997. 36,,No. 17.

US ‘186 claims Saxagliptin as a product, and it is set to expire on July 31, 2023.

It can be understand that Mylan is just applying a generic company strategy by challenging the patents by both para iv certifications and Inter Partes Review.

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FDA Approves Alirocumab To Treat Certain Patients With High Cholesterol

On July 24, 2015 FDA approved Praluent (Alirocumab) injection, the first cholesterol-lowering treatment approved in a new class of drugs known as proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors.

Praluent is marketed by Sanofi-Aventis U.S., based in Bridgewater, New Jersey, and Regeneron Pharmaceuticals Inc., based in Tarrytown, New York.

Praluent is approved for use in addition to diet and maximally tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH) or patients with clinical atherosclerotic cardiovascular disease such as heart attacks or strokes, who require additional lowering of LDL cholesterol.

Alirocumab:

Alirocumab is an investigational, fully-human monoclonal antibody that targets and blocks PCSK9. It is administered via subcutaneous injection. By inhibiting PCSK9, a determinant of circulating LDL-C levels in the blood, alirocumab has been shown in pre-clinical studies to increase the number of LDL receptors on hepatocytes, thereby lowering LDL-C.

Alirocumab was discovered by Regeneron Pharmaceuticals using its “Veloclmmune” mouse, in which many of the genes coding for antibodies have been replaced with human genes. In an investor presentation, Regeneron claimed that with their system, it took only about 19 months from when they first immunized mice with PCSK9 until they filed their IND. Alirocumab was co-developed with Sanofi under a deal made in 2007. Before it received its international nonproprietary name it was known as REGN727 and SAR236553.

About Sanofi
Sanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. Sanofi has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

About Regeneron Pharmaceuticals, Inc.
Regeneron (NASDAQ: REGN) is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions. Regeneron commercializes medicines for high LDL cholesterol, eye diseases, and a rare inflammatory condition and has product candidates in development in other areas of high unmet medical need, including oncology, rheumatoid arthritis, asthma, and atopic dermatitis.

Inter Partes Review: an extreme way to kill Patents.

Inter partes review is a trial proceeding conducted at the Board to review the patentability of one or more claims in a patent only on a ground that could be raised under §§ 102 or 103, and only on the basis of prior art consisting of patents or printed publications

Generic companies are using Inter Partes Review as a key weapon against Innovator’s OB listed patents while a patent litigation on those patents is pending in a Federal district court.

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Apotex is one of the companies which keep on targeting the Innovator’s OB listed patents by initiating IPR proceedings. And Apotex succeeded in Alcon’s Vigamox (Moxifloxacin HCl), wherein Apotex filed both paragraph IV certification and IPR against the OB listed patents of Vigamox. Further, PTAB considered the very same prior art references as the district court considered, but came to the opposite conclusion, which results in the settlement of Alcon with Apotex.

Recently Apotex filed an Inter Partes Review against the OB listed patents of Restasis® (Cyclosporine Ophthalmic Emulsion) which is approved to Allergan. Allergan listed the following patents in Orange Book for Restasis.

i) US 8,629,111 B2 (Aug 27, 2024): claims MOT an eye using topical ophthalmic emulsion which comprises 0.05% cyclosporin A, 1.25% castor oil together with various excipients.

ii) US 8,633,162 B2 (Aug 27, 2024): claims MOT an eye using an ophthalmic emulsion comprising 0.05% cyclosporin A and 1.25% castor oil together with various excipients.

iii) US 8,642,556 B2 (Aug 27, 2024): claims MOT an eye using first topical ophthalmic emulsion which comprises cyclosporin A in an amount of about 0.05% by weight, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer, water, and castor oil in an amount of about 1.25% by weight.

iv) US 8,648,048 B2 (Aug 27, 2024): claims a method of increasing tear production in the eye using an emulsion comprises cyclosporin A in an amount of about 0.05% by weight, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer, water, and castor oil in an amount of about 1.25% by weight.

v) US 8,685,930 B2 (Aug 27, 2024): claims MOT an eye of a human having keratoconjunctivitis sicca using topical ophthalmic emulsion which comprises cyclosporin A in an amount of about 0.05% by weight, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer, water, and castor oil in an amount of about 1.25% by weight.

Apotex challenged the above patents on the following grounds:

a) Claims are not novel over the disclosure of US 5,474,979;

b) Claims are obvious over the disclosures of US 5,474,979, US 5,981,607 & US 5,578,586;

wherein Apotex argued that US ‘979  teaches  the formulations of cyclosporin A in castor oil emulsions which are used in the treatment of an eye: one emulsion contains 0.05% cyclosporin A with 0.625% castor oil; and another emulsion contains 0.10% cyclosporin A with 1.25% castor oil, which is sufficient to motivate a person skilled in the art to derive the present invention with a reasonable expectation.

Further US ‘979 also teaches the use of cyclosporin A in treating immune mediated karatocunjunctivitis sicca (KCS or dry eye disease); and

US ‘607 patent teaches topical ophthalmic castor oil emulsions for the treatment of dry eye.

On July 15, 2015 Allergan confirmed that the company has received a notice letter dated July 10, 2015 (the “Notice Letter”) from Akorn Pharmaceuticals stating that theU.S. Food and Drug Administration (FDA) has received Akorn’s Abbreviated New Drug Application (ANDA) containing a “Paragraph IV” patent certification seeking approval to market a generic version of Allergan’sRestasis® (cyclosporine ophthalmic emulsion) 0.05% product.  In addition, Allergan has received communication suggesting that additional ANDAs for generic versions of Restasis® may have been received by the FDA.

The Notice Letter received from Akorn states that the “Paragraph IV” patent certification was made with respect to certain U.S. patents covering the formulation and method of use of the Restasis® product, which are listed in the Orange Book.

For more information, visit Allergan’s website at www.allergan.com.

AstraZeneca Received FDA approval For Its Lung Cancer Drug Gefitinib

On July 13, 2015, the U. S. Food and Drug Administration approved Gefitinib (IRESSA) 250MG TABLET;ORAL for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. This approval of Gefitinib is being approved concurrently with a labeling expansion of the therascreen EGFR RGQ PCR Kit, a companion diagnostic test for patient selection.

Gefitinib is a kinase inhibitor, which first approved by FDA in May 2003 for NSCLC a type of lung cancer. In June 2005 the FDA withdrew approval for use in new patients due to lack of evidence that it extended life. However, on July 13, 2015, the FDA approved Gefitinib as a first-line treatment for NSCLC.

AstraZeneca:

(According to company’s website) Oncology is a therapeutic area in which AstraZeneca has deep-rooted heritage. It will be potentially transformational for the company’s future, becoming the sixth growth platform. Our vision is to help patients by redefining the cancer treatment paradigm and one day eliminate cancer as cause of death. By 2020, we are aiming to bring six new cancer medicines to patients.

Our broad pipeline of next-generation medicines is focused on four main disease areas-lung, ovarian, breast, and haematological cancers. These are being targeted through four key platforms – immuno-oncology, the genetic drivers of cancer and resistance, DNA damage repair and antibody drug conjugates.

In lung cancer, AstraZeneca is at the forefront of development of targeted therapies, with more than 10 years’ experience in providing treatments for this challenging disease. In 2002, AstraZeneca was the first company to launch an EGFR TKI for patients with pre-treated metastatic NSCLC. We are committed to addressing the urgent unmet need for more effective treatments and are developing therapies that target all stages of the disease from primary treatment through to recurrence and re-treatment, in order to achieve sustained disease control. By making targeted, personalised treatment a reality at every stage, we hope to take important steps towards ultimately eradicating death from lung cancer.

Gefitinib:

Gefitinib is a quinazolin derivative which has the chemical name of 4-Quinazolinamine N-(3-chloro fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl) propoxy] and has the following structural formula:

Gef

Gefitinib is generically claimed in US 5,457,105 and further specifically claimed in US through US 5,770,599 (Expiry: Apr 26, 2016) wherein both the patents were issued to AstraZeneca AB.

FDA Approved Otsuka’s Brexpiprazole for the Treatment of Schizophrenia

On July 10, the U.S. Food and Drug Administration approved Brexpiprazole (Rexulti) tablets to treat adults with schizophrenia and as an add-on treatment to an antidepressant medication to treat adults with major depressive disorder (MDD).

Schizophrenia is a mental disorder often characterized by abnormal social behavior and failure to recognize what is real. Common symptoms include false beliefs, unclear or confused thinking, auditory hallucinations, reduced social engagement and emotional expression, and lack of motivation. Diagnosis is based on observed behavior and the person’s reported experiences.

Brexpiprazole:

Brexpiprazole is a quinolin derivative and it is was developed by Otsuka and Lundbeck. Brexpiprazole is patented in US through US 7,888,362 B2 (Expiry: Feb 23, 2027) which was issued to Otsuka Pharmaceutical Co., Ltd. Brexpiprazole has the following structure:

Brex

Brand vs generic: Recent Paragraph IV Patent Certifications

July 07, 2015, FDA announced that it received Abbreviated New Drug Application’s (ANDA) containing a “Paragraph IV” patent certification for the following drugs.

Drug Name Dosage Form Strength RLD Date of Submission
Abiraterone Acetate Tablets 250 mg Zytiga 4/28/2015
Linagliptin Tablets 5 mg Tradjenta 5/4/2015
Linagliptin & Metformin HCl Tablets 2.5 mg/500 mg, 2.5 mg/850 mg, 2.5 mg/1000 mg Jentadueto 5/4/2015
Posaconazole Delayed-release Tablets 100 mg Noxafil 6/16/2014

From last 10 years or more, generic companies have made the Para IV certification a routine part of doing business. The Hatch-Waxman Act regulates competition between brand-name and generic drugs in the United States. Hatch-Waxman Act actually encourages generic companies to challenge Innovator’s OB listed patents. If a generic company is the first to file its Abbreviated New Drug Application (ANDA) with a Paragraph IV certification and prevails in the subsequent lawsuit, that generic company is granted a period of market exclusivity of 180 days.

para

Generic players usually targets blockbuster drugs which has a large market potential and a patent position that could be challenged.

Previously Generic companies used to target Innovator’s products at any time before the patent is set to expire. The strategy of filing P-IV seems to be changed as the Generic’s are trying to file P-IV’s as soon as four years after a product launches (NCE-1).

Abiraterone Acetate:

Abiraterone acetate, the active ingredient of ZYTIGA is the acetyl ester of Abiraterone, which is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer. Abiraterone acetate is designated chemically as (3β)17-(3-pyridinyl) androsta-5,16-dien-3-yl acetate and its structure is:

ab

Abiraterone was first developed by Cancer Research UK and the rights for commercialisation of the drug were assigned to BTG plc, which licenced the product to Cougar Biotechnology which began development of the commercial product. In 2009, Cougar was acquired by Johnson & Johnson which developed and sells the commercial product, and is conducting ongoing clinical trials to expand its clinical uses.

JANSSEN BIOTECH received FDA approval on April 28, 2011 to market 250MG TABLET;ORAL Abiraterone Acetate under the brand name ZYTIGA, and the active ingredient is patented as a product in US through US 5,604,213 A. Further, Abiraterone Acetate received NCE which is set to expire on Apr 28, 2016. FDA received ANDA submission for ZYTIGA with a para-IV certification on April 28, 2015 (NCE-1). There is one more patent listed in OB (US 8,822,438 B2) for Abiraterone Acetate which claims MOT prostate cancer in a human using Abiraterone Acetate with the combination of Prednisone. Further, it need to be confirmed for which patent para-IV certification is filed. Currently there are 19 DMF’s listed for Abiraterone Acetate.

Linagliptin:

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2, chemically described as 1H-Purine-2,6-dione, 8-[(3R)-3-amino-1-piperidinyl]-7-(2-butyn-1-yl)-3,7-dihydro-3-methyl-1-[(4-methyl-2quinazolinyl)methyl]. The structural formula is:

Lina

Linagliptin is developed by Boehringer Ingelheim for treatment of type II diabetes. Linagliptin received FDA approval (for N201280) on May 2, 2011 for 5MG TABLET;ORAL which is marketed under the brand name TRADJENTA. Further, Boehringer received approvals for LINAGLIPTIN; METFORMIN HCl combination on Jan 30, 2012 and also received approval for EMPAGLIFLOZIN; LINAGLIPTIN combination on Jan 30, 2015. Linagliptin product is patented in US through US 7,407,955 B2 which is set to expire on Aug 12, 2023 (with out patent term extension and the application for PTE has been filed). Currently there are 13 DMF filers listed for Linagliptin.

Posaconazole:

Posaconazole is a triazole antifungal agent indicated for
i) Prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised, such as HSCT recipients with GVHD or those with hematologic malignancies with prolonged neutropenia from chemotherapy. (1.1)
ii) The treatment of oropharyngeal candidiasis (OPC), including OPC refractory (rOPC) to itraconazole and/or fluconazole. (1.2).

Posaconazole is designated chemically as 4-[4-[4-[4-[[ (3R,5R)-5-(2,4-difluoro phenyl)tetrahydro-5(1H-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[ (1S,2S)-1-ethyl-2hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one. The chemical structure is:

posa

Current P-IV certification is filed for Posaconazole 100mg Delayed-release Tablets, which received FDA approval on Nov 25, 2013 (to Merck). There are two US patent’s listed in OB for Posaconazole (100mg).
i) US 5,661,151- Claims chemical compounds, including Posaconazole;
ii) US 5,703,079- Claims genuses of chemical compounds that include the Posaconazole compound.

Previously Sandoz filed an ANDA (No 202481) to the FDA seeking approval to manufacture, use and sell Posaconazole oral suspension 40mg/ml prior to the expiration of Schering patents. Schering filed NDA Nos. 022003 and 022027 by which FDA granted approval for an oral suspension including 40 mg/ml active ingredient Posaconazole. Schering sued Sandoz on the infringment of US ‘151, US ‘079 and US 6,958,337 (claims crystalline Posaconazole).

Now its Innovator’s turn to sue P-IV players. Happy Sunday.

Did Hatch-Waxman Act Really Worked? Takeda Pharmaceuticals USA, Inc. v. West-Ward Pharmaceutical Corp (Hikma Americas Inc)

Before NEWMAN, DYK, and HUGHES, Circuit Judges; Takeda (Plaintiff-Appellant) vs West-Ward (Defendants-Cross-Appellants).

Now its Federal Circuit, which denied Takeda’s motion for preliminary injunction against Hikma pharmaceuticals for launching Mitigare, a colchicine product for prophylactic treatment of gout. Wherein Takeda sought to enjoin West–Ward Pharmaceutical Corporation, Hikma Americas Inc., and Hikma Pharmaceuticals PLC (collectively “Hikma”) from continuing its launch of Mitigare, a colchicine product for prophylactic treatment of gout, and from launching an authorized generic version of Mitigare. The appeal to Federal Circuit was actually raised from the order of United States District Court of Delaware No. 1:14-cv-01268-SLR.

Colchicine is a natural product which is extracted from plants of the genus Colchicum (autumn crocus, Colchicum autumnale). Use of Colchicine for the treatment of Gout is already known; due to its high toxicity the use of Colchicine in the therapeutic field was less known. The structure of Colchicine is given below:

Colchicine2DACS.svg

The research was carried out by AR Holding CO INC (now its Takeda) to reduce the toxicity of Colchicine in the treatment of gout. Further, Takeda received FDA approval for Colchicine TABLET; ORAL: 0.6MG which is marketed under the brand name Colcrys.

Takeda owns several asserted patents that cover several methods of administering colchicine products to treat gout. Colchicine itself, which has been used for centuries, is not covered by Takeda’s patents. US 7,964,647 and US 7,981,938 directed to methods of treating acute gout flares. US 8,097,655, US 7,964,648 and US 8,440,722 patents (the “drug-drug-interaction (DDI) patents”) are directed to methods for administering colchicine for prophylaxis of gout in patients who are concomitantly taking certain drug inhibitors known as “CYP3A4” and “P-gp” inhibitors; wherein the above said patents are listed in Orange Book for Colcrys.

In 2010, Hikma sought FDA approval of a colchicine product for prophylaxis of gout flares. It submitted an NDA under § 505(b)(2) of the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch- Waxman Act”), codified at 21 U.S.C. § 355(b)(2). On September 26, 2014, the FDA granted Hikma approval to market its Mitigare colchicine capsule.

The FDA initially objected to this omission from the Hikma label, stating that “If Mitigare is being used for prophylaxis, it may be natural for the provider to use it for acute treatment as well.” Hikma then added to its label that Mitigare was not “studied” for “safety and effectiveness” of treatment of acute gout flares. On this statement, the FDA withdrew its objection.

On October 3, 2014, Hikma launched Mitigare, and Takeda filed suit against Hikma, asserting induced infringement under 35 U.S.C. § 271(b) based on Hikma’s labeling of the Mitigare product. Hikma planned on launching an authorized generic version of Mitigare as early as October 10, 2014. However, the district court granted Takeda’s request for a temporary restraining order (“TRO”) on October 9, 2014, restraining Hikma from selling Mitigare and from launching a generic colchicine product.

On November 4, 2014, the district court denied Takeda’s motion for preliminary injunction on the grounds that Takeda did not meet its burden of showing a likelihood of success on the merits for its induced infringement claims or irreparable injury. On the issue of the likelihood of success on the merits, the district court concluded that, although Hikma failed to raise a substantial question regarding the validity of the patents, Takeda had not met its burden of showing likelihood of proving induced infringement. On the issue of irreparable harm, the district court concluded that Takeda had not shown a causal nexus between Hikma’s infringement and Takeda’s alleged harm.

Takeda timely appealed the denial of preliminary injunction, and Hikma cross-appealed.

wherein Federal Circuit states that:
Hikma elected to file a paper NDA pursuant to 21 U.S.C. § 355(b)(2). Hikma did not, however, file a Paragraph IV certification with respect to Takeda’s patents because it relied on prior FDA findings of safety and efficacy concerning colchicine, and did not seek FDA approval for a use covered by Takeda’s patents. Further, it cited Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348 (Fed. Cir. 2003), in which congress intended “that a single drug could have more than one indication and yet that ANDA applicant could seek approval for less than all of those indications. A patent certification such as a Paragraph IV certification need not be provided “for a patent claiming a use for which the ANDA applicant is not seeking approval. In such a situation, a generic manufacturer may avoid infringement by proposing a label that does not claim a patented method of use. Based on the above discussion the Federal Circuit address the question of whether Takeda showed a likelihood of success on the merits of the induced infringement claim.

However, Hikma did not seek FDA approval to market Mitigare for treatment of acute gout flares, Mitigare’s label stated that Mitigare is “indicated for prophylaxis” and that the “safety and effectiveness of for acute treatment of gout flares during prophylaxis has not been studied. Further, the label also said that if you have a gout flare while taking [Mitigare], tell your healthcare provider.

Takeda argued that this latter statement induced infringement because, in the case of the patient taking Mitigare for prophylaxis, the physician would likely tell the patient to use the Mitigare product to treat the acute flare. However, district court as well as Federal Circuit concluded that the latter instruction was not sufficient to establish induced infringement.

Finally Federal Court issued an Order which states that:

The district court’s order denying Takeda Pharmaceuticals U.S.A., Inc.’s motion for preliminary injunction is affirmed, and it further states that both parties are free to immediately offer colchicine products for prophylactic use, without regard to the 10-day provision of the district court’s order.

Vertex Pharma Received FDA approval For Its Cystic Fibrosis Drug

July 2, 2015 U.S. Food and Drug Administration approved Orkambi which is a combination of Lumacaftor 200 mg/Ivacaftor 125 mg and it is the first drug for cystic fibrosis directed at treating the cause of the disease in people who have two copies of a specific mutation.

On November 05, 2014 Vertex Pharma submitted (NDA) 206038 under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Orkambi (Lumacaftor/Ivacaftor) oral tablet at 200mg/125mg for the treatment of cystic fibrosis (CF) in patients age 12 years and older who are homozygous for the F508del mutation in the CFTR gene.

Cystic Fibrosis :
Cystic fibrosis (CF) is a genetic disorder that affects mostly the lungs but also the pancreas, liver, kidneys and intestine. Long-term issues include difficulty breathing and coughing up sputum as a result of frequent lung infections. Other symptoms include sinus infections, poor growth, fatty stool, clubbing of the finger and toes, and infertility in males among others. Different people may have different degrees of symptoms.

Lumacaftor :
Lumacaftor (VX-809) is developed by Vertex Pharmaceuticals, chemically designated as 3-{6-{[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl]amino}-3-methylpyridin-2-yl}benzoic acid. Lumacaftor is a white to off-white powder that is practically insoluble in water (0.02 mg/mL). The structure of Lumacaftor is given below:

Lumacaftor_skeletal.svg

Ivacaftor :
Ivacaftor (VX-770) was also developed by Vertex Pharmaceuticals. On Jan 31, 2012 Vertex received FDA approval for Ivacaftor which is marketed under the brand name Kalydeco. Ivacaftor is protected in US through US 7,495,103 B2 which is an OB listed patent for Ivacaftor and it is set to expire on May 20, 2027 (including PTA of 695 days). The structure of Ivacaftor is given below:

512px-Ivacaftor.svg

“We expect 2015 to be a year of rapid and significant growth in revenues based on treating many more people with CF following the potential approval and launch of the combination of Lumacaftor and Ivacaftor and further label and geographic expansion for KALYDECO,” said Ian Smith, Executive Vice President and Chief Financial Officer for Vertex.

Apotex Loses its IPR2015-00419 Against Merck’s Fosaprepitant

June 25, 2015 Judges LORA M. GREEN, ZHENYU YANG, and ROBERT A. POLLOCK denied Institution of Apotex IPR against Merck’s US 5,691,336 which claims Fosaprepitant Dimeglumine.

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IPR was filed by Apotex on Dec 11, 2014 against Merck’s US 5,691,336 A which claims Fosaprepitant Dimeglumine and also listed in OB for Fosaprepitant Dimeglumine.

US ‘336 was filed by Merck on Sep 8, 1995 claiming Fosaprepitant Dimeglumine generically which was issued on Nov 25, 1997. US ‘336 is set to expire on March 4, 2019 (including patent term extension of five years).

Fosaprepitant Dimeglumine is a prodrug of Aprepitant and it is a P/neurokinin 1 (NK1) receptor antagonist which is developed and patented (US 5,691,336) by Merck. Fosaprepitant Dimeglumine is approved in US on Nov 12, 2010 which is marketed under the brand name EMEND. The structure of Fosaprepitant is shown below:

Apotex challenged the validity of claims of US ‘336 as it is obvious over the the following documents:
i) Dorn’s US 5,637,699 which discloses Aprepitant and its use as Tachykinin receptor antagonist.
ii) Murdock’s US 5,070,082 which teaches the use of phosphoramidate moiety in the preparation of prodrugs with enhanced aqueous solubility.

Apotex argued that an ordinary skilled person will modify Aprepitant which is well known from Dorn ‘699 with the teachings of Murdock ʼ082 to derive Fosaprepitant. However, on June 25, 2015 Patent Trial And Appeal Board rejected Apotex requisition for an inter partes review of US ’336, stating that Petitioner has failed to sufficiently explain why, at the time of the ’336 patent invention, a skilled artisan would have chosen compound 96 of Dorn ’699 to further develop its prodrug, which is the subject matter of the challenged claims. Therefore, it is concluded that Petitioner has not established a reasonable likelihood it would prevail in showing any of the challenged claims would have been obvious over Dorn ’699 and Murdock ’082.

Finally, the board concluded that Petitioner has not established a reasonable likelihood it would prevail in showing any of the challenged claims would have been obvious on either of these grounds. So the IPR is dismissed.

Thanks to Harshavardhan.K for suggesting me and helping me to post this article.

Harsha.K
Harsha.K

Breaking News: One More Opposition Have Joined in Gilead’s Sofosbuvir Oppositions Saga.

Gilead’s Sofosbuvir is always in news for its cost for the treatment of hepatitis C virus (HCV) infection, Gilead’s Indian Patent Publication 3658/KOLNP/2009 covering Sofosbuvir is also making news in Pharma sector for its Oppositions.

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Patent oppositions & litigations in India in past five years (or) more have shown the strategies of Indian pharma companies, where most of the Indian companies are using them as a main weapons to tackle Innovator’s patents or patent publication related to pharmaceutical products.

Sofosbuvir is a nucleotide analog which is discovered by Pharmasset and developed by Gilead Sciences for the treatment of hepatitis C virus (HCV) infection. The price of Sofosbuvir, quoted in various media sources as $84,000 to $168,000 for a course of treatment in the U.S., £35,000 in the UK for 12 weeks which has engendered considerable controversy. In September 2014, Gilead announced that it would permit generic manufacturers to sell sofosbuvir in 91 developing countries and that it would sell a name brand version of the product in India for approximately $300 per course of treatment. The structure of Sofosbuvir is given below:

In India Gilead filed the following patent applications (main) for Sofosbuvir.

i) IN 6087/DELNP/2005 which covers Sofosbuvir metabolites.
ii) IN 3658/KOLNP/2009 which covers Sofosbuvir as a main product.

However, IN ‘6087 has been rejected by Indian Patent Office (Delhi). Gilead appealed to the Delhi High Court and the Court set aside the order and asked the Patent Office to review the case.

Recently Virupaksha Organics Limited has filed a Pre-Grant opposition against Gilead’s Indian patent application no. 3658/KOLNP/2009 on the grounds of lack of novelty Section 25 (1)(b), obviousness Section 25(1)(e), 25(1)(g) Insufficiency, 25(1)(h) and also Section 3(d) (as it is the phosphoramidate ester). However, this is not the first time IN ‘3658 is opposed, previously IN ‘3658 was opposed by Initiative for Medicines Access & Knowledge (I-MAK), Natco Pharma Limited, Indian Pharmaceuticals Alliance (IPA), Initiative for Medicines Access and Knowledge (I-MAK) and Delhi Network of Positive People (DNP+), Sankalp Rehabilitation Trust and Optimus Pharma. Natco seems to be withdrawn its Oppositions, however, there are no official confirmation as documents are available.

Natco is the 1st company in India to get approval for generic sofosbuvir tablets, 400mg, from Drugs Controller General (India).

Gilead had followed a Voluntary licensing strategy and succeded for its Tenofovir drug which is patented in India (for Tenofovir Alafenamide), used in the treatment of HIV/AIDS. Now In 2014, Gilead seems to be playing the same strategy for Sofosbuvir (Sovaldi) in India.

Its only the final decision of IPO is awaited and the it is sure that the decision of IPO on the grant of Sofosbuvir patent will effect the Indian Pharma sector.