Polymorph is the ability of a solid material to exist in more than one form or crystal structure. When a drug substance exists in polymorphic forms, it is said to exhibit polymorphism.
Polymorphism can potentially be found in any crystalline material including polymers, minerals, and metals.
Polymorph is a natural property: polymorphs are not ‘created’ or ‘invented’; they are discovered normally as part of routine experimentation related to drug formulation.
The pharmaceutical sector is a major user of the Patent system. While only a small number of new chemical entities are approved annually, thousands of patents are applied for to protect variants of existing products, processes of manufacture or, where admitted, second indications of known pharmaceutical products.
With rapid improvements in technology and drug development, keeping up to date with the latest pharmaceutical research and best practice approaches is an essential part of improving drug efficacy, safety and quality.
Must be a product of human ingenuity;
Must have novelty-not part of the “state of the art”;
Must not be obvious;
Must have utility-must serve some worthwhile practical use;
Must contain an enabling description;
Inventor gains exclusive rights.
SECOND GENERATION PATENTS
Originators are burdened with increasing cost for developing drugs.
The cost of novel drugs are perceived as too high even for developed economies.
There is a real pressure for the originators to increase the duration of their monopoly beyond the term of patent.
Generics to break that monopoly.
Second Generation Patents
These patents seek to protect a drug after the original patent on the drug has expired.
They protect some form of variation or improvement.
SECOND GENERATION PATENTS-EXAMPLES
Second therapeutic use
Complex molecules can crystallize in many ways:
Diamond, coal and carbon nanotubes are different crystal structure of the same compounds.
Polymorphism is playing an increasingly important role in establishing and protecting IPR in the pharma industry. Many drugs receive regulatory approval for only a single crystal form or polymorph.
Independent patent applications on polymorphs have become increasingly frequent and controversial, as patents thereon can be used to obstruct or delay the entry of generic competition.
The preparation, prosecution and protection of patent involving polymorph are quite challenging.
Some compounds present in polymorphic forms, i.e., they crystallize in diverse forms. Such forms can be deemed within the prior art and therefore not patentable. However, process patent may be allowed for the new polymorph, if the polymorph is prepared by a novel process involving inventive step.
Polymorphic forms of a drug substance can have different chemical and physical properties, including melting point, chemical reactivity, apparent solubility, dissolution rate, optical and mechanical properties, vapor pressure, and density.
These properties can have a direct effect on the ability to process and/or manufacture the drug substance and the drug product, as well as on drug product stability, dissolution, and bioavailability. Thus, polymorphism can affect the quality, safety, and efficacy of the drug product.
The significance of different polymorphs is almost entirely in their relative rate of dissolution.
POLYMORPHS AND PATENTABILITY
Main patentability criteria for polymorphs
-Disclosure of the invention
-Unity of the invention
A claim in the form of… crystalline form II of compound X does therefore not comply with the requirement of clarity.
Polymorphs are defined in a claim by parameter values which relate to the physical data used for defining their crystal structure.
A polymorph is defined in a claim by its physiochemical parameters
Ex: Single crystal X-ray diffraction, X-ray powder diffraction, IR spectroscopy
A crystalline tolterodine tartrate form I, characterized by an x-ray powder diffraction spectrum having peaks expressed as 2.theta. at about 11.9, 13.6, 14.2, 15.9, 16.9, 18.4, 18.8, 20.4, 22.0, 23.9, 25.4, 26.3 and 29.8 degrees.
Disclosure of the invention
The application must disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.
The invention shall be considered new if it does not form part of the state of the art.
A chemical substance is held to be new if it differs from a known substance in a reliable parameter.
An invention shall be considered as involving an inventive step if, it is not obvious to a person skilled in the art.
Unity of the invention
The application shall relate to one invention only or to group of invention so linked as to form a single general inventive concept.
RANITIDINE HYDROCHLORIDE (Zantac®)
The pharmaceutical company GlaxoSmithKline defended its patent for the polymorph type II of the active ingredient in Zantac against competitors while that of the polymorph type I had already expired .
Roche and Wockhardt
Roche got its first first pharma product patent for Hepatitis Drug Pegasys in India in 2006. Its struggle over its patents started in 2007, when India’s first post grant opposition was filed by Wockhardt and a Mumbai based NGO for “IN198952” on Pegasys attacking its validity claiming it to be non-inventive and not satisfying Section 3d. Roche could taste success with its patent by defending it successfully by clearing the “enhanced efficacy” test in the Section 3d of the Indian Patent Act.
The Glivec battle in India
It concerns the patentability of the Beta crystalline form of Imatinib, the active pharmaceutical ingredient in the blockbuster drug Glivec (Gleevec).
Kolkata Patent Office issued an Indian Patent No. 225209 to Eli Lilly & Co. for crystalline non-solvated anhydrous Arzoxifene. Lilly had been fairly successful in prosecuting and convincing Indian Patent Office (IPO) for polymorph and salt patent applications.
To ensure availability of quality medicine at affordable price, patent system should be used judiciously. Indian Patent Act 1970 that was amended in 2005 has ensured that pharmaceutical companies do not misuse the patent system. Provision of effective safeguards and its appropriate implementation would ensure balance between incentive for innovation and access to affordable medicines.