Patenting Unpredictable Arts: Issue And Challenges

In the context of patents, the term “unpredictable arts” refers to fields where the outcomes of experiments or innovations are not easily predictable. This is particularly relevant for inventions in fields like chemistry, biotechnology, and pharmaceuticals. Similarly, it is undisputed that a drug’s success in treating one type of cancer does not necessarily translate to success in treating a different type of cancer, which underscores the unpredictability of cancer treatment generally. In cases involving unpredictable factors, such as most chemical reactions, pharmaceutical activity, and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved. In biotech and pharmaceutical fields, since the degree of uncertainty and unpredictability is higher, the applicant for a patent is expected to clearly and convincingly satisfy the requirement of enabling disclosure.

This means that the scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to people of ordinary skill in the art. This mandates the applicant to describe the invention in such terms that one skilled in the art can make and use the claimed invention. It is not uncommon to believe in all jurisdictions that a PHOSITA cannot predict if a reaction protocol which works for one compound will also work for others. This factor also assists the inventor in obtaining a patent, particularly in crossing the inventive step hurdle.

If we look at the practice in the US, UK, and India, we will find that in contrast to the applied sciences, the patent offices in all jurisdictions have sought a more detailed disclosure in chemistry and the experimental sciences like biotechnology and pharmaceuticals. This puts an additional burden on the inventor to meet a high disclosure requirement where enhanced/unexpected efficacy is claimed. In India, Section 3(d) also mandates a high disclosure requirement where enhanced/unexpected efficacy is claimed, which appears to be in line with practice in other jurisdictions.

Effect of Non-Disclosure of Enabling Data

In case the applicant fails or skips this essential element during the filing of the application, the courts in other jurisdictions, including India, are likely to take a decision that may be adverse to the applicant. This factor makes these inventions susceptible to additional requirements such as enhanced efficacy or a higher level of detail to meet the requirement of description in the patent specification. It is known that inventions that use known properties or ideas in predictable ways to obtain a benefit are not patentable. Therefore, for an invention to be patentable, the inventor must show that its benefits are non-obvious and unexpected. Additionally, in a few cases, the applicants look for the fact that the result so obtained was odd with science and hence patentable. The opponent, on the other hand, seeks to invalidate the patent on the grounds of non-enablement.

Patents with unexpected results

Meeting the objections relating to similarly placed prior art during the prosecution of the application is guided by the prior art of the claimed compound and its proximity to the prior art. This means comparing the structure of the compounds nearest in the prior art, the whole compound and the properties of the claimed invention and one closest to the prior art. The striking aspect of this comparison is finding surprising improvements in the properties of an invention, as this would qualify to be considered an inventive step despite its closeness to prior art. This issue cropped up in the UK court in Olin Matheson Vs Biorex (1970 1RPC (157) (CH. D). The invention in this infringement dispute was related to trifluoro15 methyl-phenothiazine derivatives [patent No. 857,547], and the patentees claimed they had produced a useful alternative to the known tranquilliser drug chlorpromazine by substituting a trifluoromethyl-CF3 radical in place of the-Cl radical in chlorpromazine.

The defendants alleged that the patentees had only tested a small proportion of the very large number of substances falling within the claims of the specification, and they contended that, as it was impossible to predict that all the compounds included within the ambit of the claims would be likely to have any utility as drugs until they had actually been tested, there was excessive width of claim and inadequate consideration for the grant of a patent. As regards obviousness, they submitted that at the relevant date, chlorpromazine was known as a useful tranquilliser, and it would have been obvious for a drug research organisation to attempt the substitution of the -CF3 radical in order to produce an alternative and improved tranquilliser to chlorpromazine. They relied inter alia on several prior documents that they alleged would have been brought to the notice of any research group that was considering the possibility of a -CF3 substitution.

The court held that “having regard to the history of the matter and the evidence, it would not have been obvious in 1955 to make the -CF3 substitution or to arrive at a body falling within claim 1”. The court held that “it is not obvious to substitute -CF3 for -Cl at 2 positions of a phenothiazine ring system, even though the prior art compound Chlorpromazine and the claimed novel compound trifluoperazine were both tranquillisers.”  The patentee, in this case, was successful in demonstrating the non-obviousness of his patent with unexpected results. In this case, the court found that the patentee showed that its benefits were non-obvious and unexpected. It is clear from this case that an unexpected result may be demonstrated when a device or process demonstrates results that are at odds with existing science.

Unpredictability and Enablement

If the expected beneficial results are evidence of the obviousness of a claimed invention, the unexpected beneficial results are evidence of non-obviousness. The added advantage is not synonymous with synergistic effects, as it is known that for any invention to be patentable, one needs to show that its benefits are non-obvious and unexpected. The unexpected results should be proved when a device or process demonstrates results that are at odds with existing science. If the applicant is able to cross the inventive step hurdle in inventions relating to unpredictable arts like biotechnology, he is likely to grapple with heightened enablement requirements in the specification.

This requirement stepped in the patent law jurisprudence when the US Supreme Court rejected Amgen’s argument that the unpredictability of antibody discovery justified its broad claims, using the reasoning that the law does not require that all possible embodiments be tested, but it does require that the specification teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. (Amgen Inc. v. Sanofi, 143 S. Ct. 1243, 1248 (2023).

Earlier, In re Wright, [999 F.2d 1557, 1559 (Fed. Cir. 1993)]., the Board of Patent Appeals and Interferences affirmed the examiner’s rejection of application [No. 06/914,620] for a process for producing live, non-pathogenic vaccines against pathogenic RNA viruses, finding that the physiological activity of RNA viruses was unpredictable and that the applicant had not provided sufficient guidance or evidence to support the broad scope of the claims. The Federal Circuit also affirmed the rejection, holding that the applicant had not met the burden of showing that his specification enabled his invention across its full scope. This case clearly demonstrates the difficulty of enabling a broad range of processes, products, and uses based on a single example, especially in unpredictable fields such as biotechnology.

Enhanced Efficacy Entails Comparative Data: Position in the US

The need for efficacy data to support patent claims in unpredictable fields like cancer treatment is greater, as the obviousness determination depends upon finding a reasonable expectation of success. For example, in the case of OSI Pharmaceuticals, LLC v. Apotex Inc., the Federal Circuit highlighted the need for efficacy data to support patent claims in unpredictable fields like cancer treatment. This case revolves around the finding that N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazo-linamine, also known as erlotinib. [Tarceva®] was an effective targeted therapy for Non-Small-Cell Lung Cancer (NSCLC).

This was claimed in patent US 6,900,221. The decision in this case hinged on two striking facts. Firstly, the lack of erlotinib-NSCLC efficacy data or other indication of success here is significant because of the highly unpredictable nature of treating NSCLC, which is illustrated by the over 99.5% failure rate of drugs entering Phase II. Secondly, it is undisputed that a drug’s success in treating one type of cancer does not necessarily translate to success in treating a different type of cancer, which underscores the unpredictability of cancer treatment generally.

The Opposition Board observed that claims 44–46 and 53 of the ’221 patent would have been obvious over Schnur in view of Gibbs or OSI’s 10-K and ruled that these claims are unpatentable. The Board reviewed the prior art references and found that a person of ordinary skill “would have combined Gibbs or OSI 10-K with Schnur and had a reasonable expectation of success of achieving the invention of challenged claims 44 and 53.” OSI challenges the Board’s obviousness determination, arguing that the Board’s finding of a reasonable expectation of success is not supported by substantial evidence. OSI filed an appeal.

Speaking on the data relied on by the Board as substantial evidence, the court observed that

“Given this high failure rate, a fact finder could not reasonably find that the 10-K statement combined with Schnur would have been sufficient to create a reasonable expectation of success. These references provide no more than hope, and the hope that a potentially promising drug will treat a particular cancer is not enough to create a reasonable expectation of success in a highly unpredictable art such as this. Indeed, given a 99.5% failure rate and no efficacy data or any other reliable indicator of success, the only reasonable expectation at the time of the invention was failure, not success. It is only with the benefit of hindsight that a person of skill in the art would have had a reasonable expectation of success in view of the asserted reference. The Federal Circuit held that “on these particular facts, a reasonable fact finder could not find a reasonable expectation of success. The Board’s finding is thus not supported by substantial evidence, and accordingly, we reverse its obviousness determination.”

In this case, the Federal Circuit highlighted the need for efficacy data to support patent claims in unpredictable fields like cancer treatment. There is emerging, intense interest in CAR T-Cell therapies. However, this type of therapy poses unique patentability challenges. It may not be difficult to obtain patents with claims not supported by enabling disclosure where the outcomes of experiments or innovations are not easily predictable, as there is a possibility of obtaining patents based on unpredictable results.

However, the importance of providing detailed and specific information in a patent specification to demonstrate that the invention works as claimed cannot be ignored. If the applicant skips or prefers to ignore the need to enable disclosure, the challenge to the patent validity on this ground may be fatal. For example, recently, the CARTell patents relating to two blockbuster drugs viz US 7446190 (YASCARTA) and EP3214091 (KYMRIAH) came under litigation, and the form patent was invalidated on the ground of insufficient enabling description.

Facts of the YASCARTA Case

In Juno Therapeutics, INC., Sloan Kettering Institute for Cancer Research, Plaintiffs-Appellees v. Kite Pharma, Inc., Defendant-Appellant [U.S. Patent No. 7,446,190], the disputed US ’190 patent relates to a nucleic acid polymer encoding a three-part CAR for a T cell.  Juno sued Kite, alleging that Kite’s scFv that targeted CD19 infringed Juno’s patent. Kite defended by asserting that the claims in Juno’s patent were invalid for failing to meet the written description requirement. Kite argues that the asserted claims are invalid for failing to satisfy the written description requirement because the ’190 patent discloses neither representative species nor common structural features of the claimed scFv genus to identify which scFvs would function as claimed.

According to Kite, the Juno claims cover an enormous number (millions of billions) of scFv candidates, only a fraction of which satisfy the functional binding limitation for any given target, and the written description does not meet the written description requirement for this functional binding limitation. It also argues that the scFv field is unpredictable since a scFv’s binding ability depends on a variety of factors. Juno countered this, stating that scFvs were well-known (as was how to make them), that multiple scFvs for specific targets were also well-known, and the ’190 patent describes two working scFv embodiments that are representative of all scFvs, and that scFvs had been incorporated in CARs well before the ’190 patent’s priority date. Juno also argued that scFvs are interchangeable and have common structural features.

The federal court agreed with Kite’s assertion that no reasonable jury could find the ’190 patent’s written description sufficiently demonstrates that the inventors possessed the full scope of the claimed invention. This led to the court to hold that “substantial evidence does not support the jury’s finding of adequate written description for any of the asserted claims.” The US Supreme Court has denied Juno’s appeal, making the Federal Appeals Court decision the final word on this case.

Facts of the KYMRIAH Case

Similarly, EP3214091 (KYMRIAH), the University of Pennsylvania, was opposed by Public Eye and Médecins du Monde (Doctors of the World). This patent was for a new therapy of Novartis (exclusive licensee). In this procedure, the patient’s white blood cells are genetically modified to recognise and attack cancer cells before being re-injected. This therapy is indicated against certain refractory or relapsing blood cancers. The opponents claimed that the subject matter lacks novelty. However, in a surprise move, the patent holders withdrew the Kymriah patent, perhaps to avoid a discussion on the merits of their contested patent.

The above cases in the US underscore the importance of sufficient description in the patent specification to sufficiently demonstrate that the inventors possessed the full scope of the claimed invention. The side tracing of sufficient description may fetch you a patent from the patent office. However, it may face the risk of invalidation when such a patent is challenged. In that case, the invalidation is likely to happen as in Juno’s patent, where the court found sufficient description wanting, and the US’190 patent was held invalid for failing to meet the written description requirement. The US Supreme Court denied Juno’s appeal, making the Federal Appeals Court decision the final word on this case.

Enablement Requirement in Unpredictable Art: Position in India

Though the enablement requirement under the Indian patent law is critical for the opposition to patent under Section 25(1)(g), 25(2)(g) and 64(1)(h), it is the duty of the applicant to sufficiently disclose the invention as claimed.  It is known that a potential infringer can launch a “preemptive strike” against the patentee to seek a refusal of a patent application under Section 25(1)(g) or revocation of the patent under Section 64(1)(h) on the ground of enablement which states that:

25(1)(g) and 25(2)(g)

“(g) that the complete specification does not sufficiently and clearly describe the invention or the method by which it is to be performed;”

Section 64(1) (h)

“(h) that the complete specification does not sufficiently and fairly describe the invention and the method by which it is to be performed, that is to say, that the description of the method or the instructions for the working of the invention as contained in the complete specification are not by themselves sufficient to enable a person in India possessing average skill in, and average knowledge of, the art to which the invention relates, to work the invention, or that it does not disclose the best method of performing it which was known to the applicant for the patent and for which he was entitled to claim protection”

If the inventor prefers to skip the enablement data, he may do so at their own peril, as they may face the rejection of the patent application as happened in Ovid Therapeutics, Inc. v Assistant Controller of Patents. Delhi High Court case. The India patent application of Ovid for “Methods of increasing tonic inhibition and treating secondary insomnia” was refused by the Patent Office inter alia under Section 3(d). Ovid challenged this refusal. Under this appeal, the question before the Delhi High Court was whether the claimed composition resulted in enhanced therapeutic efficacy.

Since the results of phase 3 trials available to the applicant had not been placed on record, the Court ruled that such results were necessary to determine the efficacy of the composition. Therefore, the court held that there was insufficient data to demonstrate a significant enhancement of the therapeutic efficacy of the claimed invention. In this ruling, the Delhi High Court joins with the precedence set by US cases discussed above to affirm the meeting of the requirement of sufficiency by the patent applicant to avoid rejection of the patent.

Unpredictable Cancer Treatment Involving Deactivation of T-Cells

This aspect of the unpredictability of results has been used in many cases to seek patents. For example, when a patent application was submitted for a cancer treatment that involved the deactivation of t-cells, a form of white blood cell that typically attacks cancer cells. This basically involves Chimeric antigen receptor T-Cells (CAR T) containing living cells. CAR T-Cells are genetically modified antigen-specific immunotherapies that are generated to express the particular antigen that is affiliated with the diseased cells. It fluctuates based on a person’s genes and the particular cancer cells that make up the disease. This type of cancer treatment involved the deactivation of the very cells that most doctors would seek to preserve. Such a process demonstrates results that are at odds with existing science and are found to be a completely counterintuitive, non-obvious idea. And thus, patentable.

CAR T-Cell Technology:  Patent Granted in India

Many patents relating to various innovative aspects of the unpredictable CAR T-Cell technology have been granted in the US and other jurisdictions, including India. However, the Indian patent office prosecution history of IN449337 follows a pattern that seeks the applicants to restrict the claims of CAR T-Cell technology to narrow and specific subject matter. In the instance case, the applicant restricted the claims to (a) the components of the CAR T-Cells, (b) the CAR-T-cells themselves, (c) methods of manufacturing CAR T-Cells, and (d)methods of using CAR-T-cells.

It may be noted that the claims that covered a broad genus without sufficient guidance or examples are not permitted in India, as well under the objection of sufficiency (Section 10(4)). The examiners in India are following the reasoning of Amgen Inc. v. Sanofi to a certain extent, as there is no such precedence on this issue in India. In the absence of specific guidelines, examiners in India, by default, look to the West to keep claims relating to unpredictable inventions like the CAR T-Cell under check using the insufficiency objection.

If a nucleic acid is claimed, it should be defined by the specific nucleic acid sequences rather than the sequences of the TCR alpha chain and/or a TCR beta chain, and it encodes as it happened in IN 524360. In this case patent was allowed after the applicant amended the claims to read as “A T-Cell receptor (TCR) having the property of binding to a SLLQHLIGL (SEQ ID NO: 1) HLAA*02 complex and comprising a TCR alpha chain variable domain and a TCR beta chain variable domain each of which comprises FR1-CDR1-FR2- CDR2-FR3-CDR3-FR4 where FR is a framework region and CDR is a complementarity determining region…..”.

It may be noted that the claims falling under Section 3(c) for naturally occurring substances, Section 3(d) for new forms of known substance Section without showing enhanced efficacy, Section 3(i) for medical method/ treatment, and Section 3(j) for plants, animals and part thereof are not patentable in India and hence they are required to be deleted. A representative list of the patents granted for inventions relating to CAR T-Cell technology in India is given below.

Parting Remarks 

One of the primary requirements for obtaining a patent is enablement. This requirement was imputed in patent law because the fields of organic chemistry, biotechnology, and pharmaceuticals are essentially experimental science, and results are often uncertain, unpredictable, and unexpected. We have seen that the Courts in the US have applied the new standard for enablement and written description, as established in the Amgen case, to patent cases involving different technologies and claim types. If the applicants’ claims are narrow and specific, the US courts have generally upheld the validity of the claims. The examiner in India also seeks to apply a strict standard that requires enablement (sufficiency) matching the full scope of the claimed embodiments in most cases.

When this question is raised in the biotechnology field, where the claims cover a broad genus of compounds or antibodies without sufficient guidance or examples, the examiner would invariably insist the applicant restrict them to narrow and specific claims, as supported by the details in the patent specification. In cases involving unpredictable factors, such as most chemical reactions, pharmaceutical activity, and physiological activity, the scope of enablement obviously varies. In biotech and pharmaceutical fields, since the degree of uncertainty and unpredictability is higher, the applicant for a patent is expected to clearly and convincingly satisfy the requirement of enabling disclosure.

This means that the scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art. This mandates the applicant to describe the invention in such terms that one skilled in the art can make and use the claimed invention. If we see the decided cases in the US, UK, and India discussed above, we will find that in contrast to the applied sciences, the judiciary in all jurisdictions has required a more detailed disclosure in chemistry and the experimental sciences like biotechnology and pharmaceuticals. In India, Section 3(d) also mandates a high disclosure requirement where enhanced/unexpected efficacy is claimed, which appears to be in line with practice in other jurisdictions.

There is emerging, intense interest in CAR T-Cell therapies, and the number of such applications is growing in India. We have seen that patenting this type of therapy poses unique patentability issues and challenges. In some instances, it may be difficult to obtain patents if claims are not supported by enabling disclosure and in other case patents may be revoked if the court finds that the claims are not sufficiently enabled. In any case, a claim must be enabled by the specification, which discloses working examples and general guidance for applying the method. It is not uncommon to believe in all jurisdictions that a PHOSITA cannot predict if a reaction protocol which works for one compound will also work for others.

These factors may assist the inventor in obtaining a patent, particularly in crossing the inventive step hurdle. However, it puts an additional burden on the inventor to meet a high disclosure requirement where enhanced/unexpected efficacy is claimed. In case the applicant fails or skips this essential element during the filing of the application, the courts in other jurisdictions, including India, are likely to make a decision that may be adverse to the applicant, as happened in the cases discussed above. Expert guidance in drafting patent specifications in unpredictable fields would be useful in obtaining a strong patent. It would help to provide innovators with adequate protection for such inventions.

Author: DPS Parmar

First Published by: Mondaq here