Showing posts with label Market. Show all posts
Showing posts with label Market. Show all posts

Saturday, 29 August 2015

Polymorphisms and Patent, Market, and Legal Battles:  Cefdinir Case Study

Abstract Image

Cefdinir is a third-generation oral cephalosporin antibiotic sold under the brand names Cefzon and Omnicef
As of 2008, cefdinir, as Omnicef, was the highest-selling cephalosporin antibiotic in the United States, with more than US$585 million in retail sales of its generic versions alone.[1]
It was discovered by Fujisawa Pharmaceutical Co., Ltd. (now Astellas) and introduced in 1991 under the brand name Cefzon.[2][3]Warner-Lambert licensed this cephalosporin for marketing in US from Fujisawa.[4] Abbott obtained U.S. marketing rights to Omnicef (cefdinir) in December 1998 through an agreement with Warner-Lambert Company.[5] It was approved by FDA on Dec 4, 1997.[6] It is available in US as Omnicef by Abbott Laboratories and in India as Cednir by Abbott, Kefnir by Glenmark and Cefdiel by Ranbaxy.

The ongoing patent battle relating to Cefdinir polymorphism and crystalline forms is described from a scientific point of view. This case study illustrates some of the strategies adopted by generic bulk manufacturers to challenge originator's patents on polymorphic forms. 

The filing of patents claiming new crystalline forms, usually 4−6 years after the original product patent, is a typical strategy applied by such companies to extend patent protection. This patent protection approach by big pharma forces generic bulk producers to discover and file patents on new polymorphs if they want to market the drug after expiry of the product patents. 

Polymorphism is of paramount importance due to its effect on some physical characteristics of powders such as melting point, flowability, vapour pressure, bulk density, chemical reactivity, apparent solubility and dissolution rate, and optical and electrical properties. In other words, polymorphism can affect drug stability, manipulation, and bioavailability

The patent strategy adopted by Fujisawa to protect the life cycle of Cefdinir (1) was based on the filing of a second patent, several years after the product patent, covering the commercialised anhydrous crystalline form of the drug. As a consequence, to overcome the Cefdinir (1) patent protection of the U.S. and Japanese markets, generic bulk producers had to discover a new crystalline form, with the same bioavailability as the marketed one. 

The situation, with competition among several companies, resulted in the generation of a patent “tangle”. In addition to overcoming the Fujisawa patent, the principal aim of generic bulk producers was to generate a competitive market advantage by protecting their new crystal form.

This patent extended the protection of Cefdinir (1) marketed in the United States up to December 2011, 9 years after the expiration of the patent covering the structure........Abbott US2005/0059818

An invention must:
A. be novel.
B. not be obvious for a person skilled in the art
C. be useful.
D. contain sufficient details to allow others to reproduce the invention.
Crystalline form patents represent a small but very important segment of product patents because of the possibility to extend the medicine market protection, thus delaying competition from generic firms. We think that for these specific types of patent applications, the following basic rules should be applied:
1. The crystalline form cannot be characterised by a single technique.
2. When a pharmaceutical application or advantage is claimed to justify the usefulness of the patent application, volatile impurities must comply with ICH guidelines,23 and the new crystalline form must be sufficiently stable to be used as a medicine.
3. A new polymorph must have an advantage over the one previously described. All the patent applications described in this paper do not show a clear advantage of the claimed polymorph with respect to Fujisawa's anhydrous form. The claiming of a crystalline form or solvate without a clear understanding of the usefulness is common to several patent case studies. From our direct experience, an interesting example is Cabergoline (Parkinson's disease):  the originator and generic companies claimed up to 14 crystalline forms and solvates.24 What is the meaning of all these patent applications? Where is the advantage with respect to the previously reported crystalline forms or solvates?
Figure The priority filing dates of all the patents claiming Cefdnir crystalline forms are reported.

Astellas Pharma Inc. (アステラス製薬株式会社 Asuterasu Seiyaku Kabushiki-gaisha?) is a Japanese pharmaceutical company, formed on 1 April 2005 from the merger of Yamanouchi Pharmaceutical Co., Ltd. (山之内製薬株式会社 Yamanouchi Seiyaku Kabushiki-gaisha?) and Fujisawa Pharmaceutical Co., Ltd. (藤沢薬品工業株式会社 Fujisawa Yakuhin Kōgyō Kabushiki-gaisha?).


Polymorphisms and Patent, Market, and Legal Battles:  Cefdinir Case Study

Antibioticos S.p.A., Research & Development, Strada Rivoltana km 6/7, 20089 Rodano, Milano, Italy
Org. Process Res. Dev., 2007, 11 (1), pp 64–72
DOI: 10.1021/op0601060