Introduction

Polymorphs are compounds that can exist in two or more crystalline structures with the same chemical composition but different molecular arrangements. These variations result in differing physical properties such as solubility, and dissolution rates, making polymorphs especially important in industries like pharmaceuticals, agrochemicals, and pigments.

For pharmaceutical companies, securing patents for polymorphs in addition to the primary drug can be beneficial, as it extends patent protection. While theoretically, each new polymorph offers additional patent duration, the practical reality can be complex. Specifically, Indian Patent law does not grant protection to polymorphs unless they demonstrate significant therapeutic efficacy.

In this blog, we will explore the requirements for patenting polymorphs and their preparation methods under the Indian Patents Act and the prevailing practices, considering recent judicial developments.

What are Polymorphs and Why do they Matter?

Pharmaceutical companies often develop a mixture of crystalline forms of a drug such as alpha, beta, or gamma forms, and obtain patents on it. This practice is generally known as “evergreening”, as it intends to prolong patent protection beyond the initial 20-year term. This approach is criticized by generic manufacturers as it delayed the entry of the generic version of the patented drug even after the expiry of its patent term of 20 years.

According to the Indian Patents Act, 1970 (hereinafter, “Act”), a polymorph made in a routine manner without unexpected property is unlikely to be considered inventive. Therefore, seeking a patent for polymorphs obtained through isolation and screening in a routine manner is not worthwhile as it may fail the inventive step test under Section 2(1)(ja) of the Act and additionally, may not satisfy Section 3(d). On the other hand, a novel process for obtaining a polymorph is more likely to support an inventive step.

Patentability of Polymorphs in India

Under the Indian Patents Act, a polymorph can be patented if it meets the criteria outlined in Section 2(1)(j), which includes demonstrating Novelty, an Inventive Step, and Industrial Applicability. In India, patenting a polymorph also necessitates a complete disclosure of its composition and differentiation from other polymorphic forms to ensure clarity and sufficiency. Therefore, while filing a patent application for a polymorph or its preparation method, the applicant must provide a detailed and clear description of the polymorph and the method. This includes the conditions under which the polymorph is obtained and any specific characteristics that distinguish it from known forms.

Section 3(d) and its Importance

The polymorph compounds and their preparation methods must also comply with the requirements outlined in Section 3(d) which is designed to prevent the ‘evergreening of patents’ so that only those derivatives that demonstrate significantly enhanced “efficacy” over the known polymorph be patented.

Section 3(d) states: “the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known substance or of the mere use of a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant. Explanation – Salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations, and other derivatives of known substance are considered to be the same substance unless they differ significantly in properties with regard to efficacy.”

To fulfill the requirements of Section 3(d), Applicants must provide experimental data in the specification that demonstrates significantly enhanced “efficacy” of the claimed polymorph (in the case of pharmaceutics, “efficacy” will be “therapeutic efficacy” only) over the known polymorphs. Additional experimental data may be submitted later during prosecution through an affidavit. Still, it will be allowed only when there is some prior basis in the originally filed specification.

Patentability of Novel Processes for Polymorphs

If the claims relate to a process for preparing a novel polymorph, Section 3(d) may not apply, provided the process results in a new product with improved properties. However, Applicant must still establish inventiveness by showing that the process steps/parameters are not disclosed in any of the cited prior art, nor do they provide any hint, or that the process results in a new product that has better properties.

If the process is for preparing a known polymorph, the novelty of the claimed process needs to be established. Further, to overcome the inventive step and Section 3(d) rejection, the Applicant must show that the claimed process results in a better yield of the product, or that the purity of the product is better, or that the product has better properties when compared with the prior art process (technical advancement) by way of providing comparative experimental data.

Judicial Precedents: Key Case Summaries

In F. Hoffmann-La Roche Ltd. vs. Cipla Limited¹, the Delhi High Court emphasized that even if the non-obviousness of an invention in the pharmaceutical or chemical industry is established, the applicant should also prove that if the invention claimed is the derivative of a known substance, it does not fall within the excepted category, in the Explanation to Section 3(d) as it comprehends a discovery of significant enhancement in known efficacy of such known substance.

In Novartis AG vs. Union of India & Ors², the Supreme Court clarified that the ‘efficacy’ referred to in the explanation of Section 3(d) means ‘therapeutic efficacy’. This case has set a high bar for proving enhanced efficacy in polymorphs.

In Abbvie Inc v Deputy Controller of Patents & Designs³, the Madras High Court ruled that polymorphic forms of a parent compound, which became publicly known after the priority date of the claimed invention, do not qualify as a ‘known substance’ under Section 3(d). The court acknowledged that structural differences in the chemical composition can exclude certain polymorphs from prior art, allowing them to be patented.

In DS Biopharma Limited v. The Controller of Patents and Designs⁴, the Delhi High Court established the importance of identifying the ‘known substance’ and the ‘known efficacy’, in determining the applicability of Section 3(d). Merely because the claimed invention is a polymorph of a compound that is previously patented, does not automatically render the compound a ‘known substance’, unless the compound is published before the priority date of the claimed invention.

Patentability of Polymorphs in Other Jurisdictions

European

In Europe, polymorph patenting is stringent. Naturally occurring polymorphs may not qualify for patent protection since they could be considered disclosed in prior art.

However, new processes that yield novel polymorphs with inventive steps can be patented.

The European Patent Office (EPO) requires detailed experimental data to support claims of unexpected properties or improvements. For instance, stability data and other unique properties against polymorphic forms of a compound have supported inventive steps in various EPO cases.

United States

In Grünenthal GmbH v. Alkem Labs. Ltd.⁵, the ground of obviousness was raised to invalidate US 7,994,364. The polymorphic compound in question was tapentadol hydrochloride (tapentadol) directed to Form A of tapentadol hydrochloride. The Federal Circuit affirmed a district court finding that a patent was not invalid for obviousness. The court acknowledged the fact that tapentadol was a polymorphic compound that was unknown in the art at the time and prior art alone provided insufficient guidance as to what particular solvents, temperatures, agitation rates, etc., were likely to result in Form A.

However, the Federal Circuit categorically stated, “[O]ur decision today does not rule out the possibility that polymorph patents could be found obvious.” If it is found lacking inventive step patent is mostly denied.”

Practical Advice for Patenting Polymorphs

To maximize the chances of patenting polymorphs in India:

Ensure the polymorph demonstrates significantly enhanced efficacy over known forms, especially in pharmaceutical applications where therapeutic efficacy is critical.
Provide detailed descriptions and experimental data in the patent specification to avoid objections during prosecution.
If seeking to patent a process for creating a polymorph, focus on demonstrating the novelty and advantages of the process, including improved yield, purity, or other technical advancements.

Conclusion

Patenting polymorphs and their preparation methods in India require a thorough understanding of patentability criteria. By ensuring that polymorphs and their preparation methods meet the requirements of Section 3(d) along with the standards of novelty, inventive step, and industrial applicability, inventors and companies can secure valuable protection for their inventions.

Further to avoid any added subject matter objections during prosecution, the polymorph’s physical and chemical parameters should be disclosed. As always, to be inventive over the prior art, it must be made plausible in the application that the polymorph displays an unexpected effect/efficacy that distinguishes it from the amorphous and/or other crystalline forms of the prior art so that the claimed polymorph is not merely seen as an arbitrary selection from equally suitable candidates.

Having a secondary patent with the scope of a compound patent and extended patent lifetime can be rewarding for patent owners as an additional basis to enforce their rights against patent infringers. lifetime can be rewarding for patent owners as an additional basis to enforce their rights against patent infringers.