This article is written by Ms. Srikrishna Samhita Yadati a Second Year B.A.LL. B student of ILS Law College, Pune

Abstract

This article explores the rising importance of combination drug therapies, merging biological products, drugs, and medical devices for enhanced patient care. It emphasizes the challenges in obtaining patent rights for these combinations, focusing on antibody therapies. A case study involving Ranbaxy Laboratories highlights the complexities in patenting a non-interacting drug combination, with disputes over novelty and non-obviousness. The article underscores the need for a strong understanding of patent laws and the creation of strategic patent portfolios. It concludes that careful consideration of functional properties and thorough freedom-to-operate searches are crucial for successful patenting in the evolving landscape of combination drug therapies.

Keywords: Combination Drug Therapies, patent rights, antibody therapies, Ranbaxy Laboratories, freedom to operate search.

Introduction

The development of combination drug therapies or combination products is on the rise and they are being highly encouraged in most developing nations. They are increasingly incorporating new cutting-edge, novel medical technologies that are very helpful in boosting patient care. As the name itself suggests, a combination product is essentially an amalgamation of biological products, drugs and medical devices for the betterment of the patient’s health. The blending of these medical resources has given pharmaceutical companies tremendous therapeutic opportunities. These combination products have the potential to ensure secure treatment of patients along with effective and acceptable therapeutic benefits. Some of the examples of combination products are drug-eluting cardiovascular stents may reduce the need for repetitive surgeries, proteins incorporated into novel orthopaedic implants that can facilitate bone regeneration, etc. Combination drug therapies have proven to be highly effective in the domain of curing cancer and developing antibody therapies. The most common example of this would be treating early-age breast cancer with surgery combined with radiation therapy or any other drug therapy. This emphasises the efficacy of combination drug therapies and their growing role in the medical field.

Now that the significance and usefulness of combination drug therapies have been established, there is a growing to protect them as well. That is done by none other than IPR legislation, specifically patent laws. Acquiring patent rights for combination products can attract many challenges because it may become difficult to identify the grounds of non-obviousness and novel steps as they might be a combination of already patented drugs or clinical devices. While in an amalgamation process, the specific preparation of components in a product itself may be novel and independent which may result in new scientific use of that product itself and it may not pose much of the developmental challenges. However, the former problem remains persistent today due to the complex combination of procedures of medical resources. Therefore, there is a need for the makers of combination products to get a complete understanding of patent laws so that they can easily reap the benefits and cover incremental improvements.

Antibody Combination Therapies: Patenting Process

Since the last two decades, there has an exponential growth in the number of antibody combination drug therapies in the pharmaceutical market. The estimated global market value of monoclonal antibody therapeutics was US$115B in 2018 and was expected to reach US$300B by 2025. Especially in the USA, the most prescribed medication is antibody therapy. Amidst the fuelling growth of these combination therapies, it is important to note that there are certain intellectual property concerns that they may pose. It often becomes difficult to obtain patent rights with claims that provide innovators with protection for their inventions. In many instances, the patent examiner may reject the patent applications for antibody combination since they may involve the composition of the already known therapeutic agent and an antibody that are obvious and well-studied. 

A major challenge faced by the antibody combination therapies is the test of obviousness, i.e., whether a proficient craftsperson would have had a basis to integrate the lessons from existing references to create the described invention, and it can be reasonably expected that such a skilled individual would achieve success by combining these teachings. The best way to reflect this problem is the analysis given by the Patent Trial and Appeal Board (PTAB) in the USA in various cases of patentability of such therapies. For instance, a patent related to treating cancer using a combination of an antibody (anti-ErbB2) and a toxoid compound was challenged and the court upheld this challenge by affirming the claimed invention is not patentable since it was obvious. This was further supported by the arguments that the combination described in the patent was already suggested in prior research. The Patent Trial and Appeal Board (PTAB) agreed, stating that earlier studies in mice showed a positive interaction between the antibody and the toxoid. The patent owner tried to show that the method was not obvious by presenting evidence of commercial success, unexpected results, and a long-standing unmet need. However, the PTAB rejected this evidence, stating that it wasn’t directly related to the claimed invention.

This is one such case where the challenge of obviousness was raised but there may be other significant challenges that can come in the way of patenting antibody combination drug therapies. One possible way out of this dilemma would be to specify the functional properties of such therapeutic agents. This will give clarity on the combination product and will enhance the identification of already patented or obvious drugs.

Directives for Patenting Combination Products

The significance of combination products has been substantially discovered with increasing technologies from various fields ranging from gene therapy, biotechnology, medical equipment and nanotechnology. These composite devices have provided people with necessary treatment be it a chronic disease or a severe ailment while minimizing the side effects. Due to the majestic success of these combination remedies, many academic institutions and pharmaceutical companies have employed various mechanisms to foster their development along with protecting them through patent portfolios. Integrated patent and regulatory bodies have time and again emphasized the advantages of congregating technologies in the igniting success of the combination drug market.

A strategic patent portfolio can bring huge commercial success for the companies involved in manufacturing combination drugs. It is vital for the company’s sustenance. Patent provides many business remunerations including profitable collaborations with other companies. In India, the Patent Act, of 1970 grants patent rights to combination products under section 3(d). This provision allows for the patenting of new procedures using a known substance, even if that substance is not novel or non-obvious. Additionally, data exclusivity is also ensured which prevents other companies from plagiarising the information generated out of research. In this sense, India’s patent portfolio can be claimed to be strong but challenges persist. One challenge is that it can be difficult to determine whether a particular combination of drugs is novel and inventive. This is because the prior art may include a vast amount of information about the individual drugs in the combination, but it may not be clear whether the combination itself is novel or non-obvious.

Before any product development begins, conducting a freedom-to-operate search on every component of the chemical entities is something that has been strongly encouraged. This is crucial to determine whether the pharmaceutical company has abstained from any third-party patents and is free to go ahead with its invention. The FTO search must include all the IP assignments like trademark and copyright. This step will inherently restrict companies from infringing any third-party patents found. Another effective way of patenting is by establishing ownership boundaries outright for companies indulging in joint ventures. If a company claims to own a medicine and another company claims to own a medical device, then it may raise issues of ownership of combination products. Therefore, it is safe for the companies involved in such a collaboration to disclose the rights related to combination products at the outset of their relationship. Many such creative ways can be formulated to ensure operative patent systems for combination drug therapies.

Case Study

In the case of Ranbaxy Laboratories Ltd Versus the Controller of Patents & Designs Intellectual Property Office & Others, an appeal was made against the dismissal of the opposition to a patent application for treating hyperlipidaemia in mammals using a non-interacting drug combination. This appeal was made to the Intellectual Property Appellate Board and the chairman was Prabha Sridevan. The core invention involves a non-interacting drug combination of a specific HMG-CoA reductase inhibitor and a drug affecting cytochrome P450, primarily for treating hyperlipidaemia, especially in individuals undergoing immunosuppressive chemotherapy. The patent includes specific dosage ranges and potential combinations with other drugs.

The appeal revolved around whether the combination was an obvious usage of existing knowledge or was it a non-obvious application resulting in an inventive step. The patentee’s main argument is that rosuvastatin is minimally metabolized by a certain enzyme, making it different from other statins and reducing the risk of side effects. However, opponents bring up studies showing uncertainties about the exact causes of myopathy (muscle-related issues) and challenge the patentee’s assertion. The key arguments made by the respondents were that the combination is novel, safe, and non-interacting, providing advantages over existing therapies. Whereas the appellant claims the combination is obvious, presenting prior art and studies suggesting potential risks and lack of synergy.

The chairman upheld the decision of the Controller who confirmed the rejection of the patent. The rationale given by the chairman was that the crux of the invention lies in combining a chemical entity called Rosuvastatin with other drugs and since for a pharmacologist it only takes a routine experimentation to initiate a metabolic pathway of a drug, it becomes an obvious invention. After the metabolic pathway of the drug is known, a skilled person would be able to combine it with drugs that are metabolized by different enzymes, to obtain a non-interacting combination. The critical view is that the case involves a nuanced evaluation of scientific evidence, expert opinions, and the interpretation of prior art. The decision to reject the patent indicates that the patent office was not persuaded by the patentee’s arguments, possibly due to the challenges raised by opponents based on later studies and the perceived lack of novelty in the claimed combination.

Conclusion

There is a growing significance of combination drug therapies in the medical field, incorporating biological products, drugs, and medical devices to enhance patient care. The focus is on the challenges of obtaining patent rights for these combination products, particularly in the context of antibody combination therapies. The case study of Ranbaxy Laboratories Ltd Versus the Controller of Patents & Designs involving the appeal against the dismissal of a patent application for a non-interacting drug combination further illustrates the complexities in obtaining patent rights for such medical inventions. There is a need for a comprehensive understanding of patent laws by makers of combination products to navigate challenges related to non-obviousness and novelty. It is also important to evolve a strategic patent portfolio for commercial success, with a particular focus on antibody combination therapies. The case study underscores the difficulties in proving the non-obviousness of such combinations, indicating that routine experimentation may be a determining factor in patent eligibility. A careful consideration of functional properties and a thorough freedom-to-operate search can contribute to successful patenting.

Reference

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