Drug substances patents

Polymorphism is critically important in the design of new drug API [9] and affects a number of areas. The main impact is to the bioavailability and release profile of a drug substance into the body. This is due to differences in solubility and dissolution rate, between the polymorphs. The chemical and physical stability of the formulated drug substance is also dependent on the polymorphic form. Patented registration of all discovered forms and their manufacturing conditions is an important element in protecting a pharmaceutical companies intellectual property. 

For patents that claim a drug substance or drug product, the applicant shall submit information only on those patents that claim a drug product that is the subject of a pending or approved application, or that claim a drug substance that is a component of such a product. 

For purposes of this part, such patents consist of drug substance (ingredient) patents, drug product (formulation and composition) patents, and method of use patents. 

Patents Not Claiming the Approved Drug Substance, Drug Formulation or Use... 

Brand-name companies also have listed patents that claim a drug substance differing from the approved drug substance in some way. These patents generally fall into three subcategories metabolites, polymorphs, and intermediates. Each subcategory raises its own specific issues, as elaborated below. 

An examination of two listed product-by-process patents illustrates this latter point. Patent Nos. 6,063,927 (the 927 patent) and 6,172,233 ( 233) both claim paroxetine hydrochloride made according to specified processes. In each case, the patent itself acknowledges that paroxetine hydrochloride was well known at the time the brand-name company applied for the patents. The brand-name company represented to the Patent Office in the patent document that the recited process was new and made the claims patentable. Therefore, if valid, these patents cover only those products (paroxetine hydrochloride) made according to the specified process, just as process patents cover products made according to the specified process. In contrast, product patents, such as listable drug substance and formulation patents, cover a product regardless of the process by which it is made. Thus, product-by-... 

The most widely used method of challenging the legitimacy of the process used to manufacture the generic product is to undertake an impurity profile study of the drug substance extracted from the competing product, in short to check its impurity fingerprint vs. your own product. Most companies can describe cases. One in my experience occurred when an Italian company decided to market Amikacin, at that time a patented Bristol-Myers product, in Korea. 

Other types of drug-related patents include process, use, and formulation patents. Chemists are responsible for process patents, which describe an improved method of preparation of some drug substance but are minimally involved with the others. Use patents are based on the discovery of some unobvious utility of a compound that is either part of the public domain or covered by an existing patent such discoveries are most likely to be made by biologists. Formulation patents disclose a preferred means of drug delivery of a known drug substance. 

Finally, impurity analysis can also be utilized to demonstrate illegal use of patented reaction routes. The impurity profile of a drug substance is influenced by the synthetic route and the source and quality of the starting materials. Identification of impurities in drug prepared by two different manufacturers may provide valuable insight into the manufacturing route and determine if patent infringement has occurred, because certain impurities may be indicators of a specific synthetic route. 

Optimal routes are developed to manufacture inexpensive bulk drug substance or final product over the lifetime of a patent or longer. The development of these cost-effective routes can justify the expense of many years of work. Laboratory processes are developed and examined on scale, and they evolve into optimal routes that are cost-effective, rugged, and forgiving. The optimal routes are filed with the FDA but may not be disclosed elsewhere. 

Chemical patents are granted for either composition of matter or processes. Composition of matter patents are filed early in the development of a compound. If the route to prepare large amounts of drug substance is significandy different... 

Various strategies are pursued by pharmaceutical companies to extend the product life cycle. Under the Hatch-Waxman Act, patent term extensions are available for patented drug substances, drug products, method of use, and method of manufacturing to compensate for the time lost in the FDA s regulatory approval process. However, the limitations of the statute of the following aspects have to be considered ... 

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