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.


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:


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 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:


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 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:


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.

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