The term Markush owes its existence to Eugene A. Markush, who was the applicant in US patent *720. He used it in a claim, a type of definition of a genus or subgenus by enumeration of species. In fact, this practice was in use before the rejection of such types of claims in the Markush application. The reason for the rejection of this type of claim in this case was that the examiner considered this claim to be a mere alternative in form. On petition before the commissioner (Ex parte Markush, 1925 CD 126 (Com. Pat. 1924), the form of claim was approved, and the petition was allowed, thus requiring the examiner to examine it for patentability. Thus, the name “Markush” became attached to a type of claim expression, and that is all it connotes. However, further decisions and opinions on similar petitions and appeals ensued after the Markush ruling, and a considerable body of case law evolved, approving and disapproving various forms of Markush-type expression, from which cases a number of rules can be deduced.
Definition of Markush
The term Markush is not defined in the Patent Act in any of the jurisdictions, but its use is prevalent in all the countries where the claim drafter uses disclosure of a chemical compound by identifying its chemical formula, name, structure etc. The genus is the discovery of a core structure, which is a manmade molecule that is not found in nature, and it is called a breakthrough invention. For example, inventions in pharmaceutical research are well-known as New Chemical Entity forms, which form the basis of a genus patent represented through a core or a Markush formula. Similarly, in chemical cases, claiming a genus is expressed as a group consisting of certain specified materials. This type of claim drafting is used when there is no commonly accepted generic expression which matches and covers the scope of the invention with the field in which the applicant desires to protect under one patent application.
Markush Claims Defined
According to the Guidelines issued by the United Nations Development Programme for Pharmaceutical Patent Examination: Examining Pharmaceutical Patents from a Public Health Perspective In 2015, a “Markush claim” is defined as a patent claim that “consist[s] of a generic chemical structure with multiple alternatives that allow for the protection, under a single patent, of several variants of a claimed invention,” often encompassing “several million molecules.”
Enabling disclosure and Markush claims
It is known that Markush claims cover a large range of compounds, and some Patent jurisdictions believe that such a large set of claims should not be allowed. The main reason for this view seems to be based on a belief that it is impossible to perform a prior art search for a claim encompassing so many permutations. Therefore, they believe that the patent grant to such claims should be limited to what has been actually disclosed and supported by the examples provided in the specification. Fair enough, the coverage of the patent should be limited to the claimed embodiments that are actually enabled by the disclosure in the specification. This means that a Markush claim’s patent eligibility must be proved by its enabling disclosure. Further, all variations covered by the claim must be actually enabled.
Markush practice in USPTO
Under U.S. patent law, a claim is only valid if it is “enabled” across its full scope. This enablement requirement is applicable to Markush claims as well. There appears to be no statutory requirement under U.S. law for an inventor to actually synthesized and characterized each and every molecule falling within the scope of the Markush claim. This means the inventor would meet the requirement if disclosure is sufficient enough to enable one of skill in the art to make and use the full scope of the invention without engaging in undue instrumentation. Thus, it is possible for a claim to be enabled where it covers even millions of compounds and the vast majority of which have never been synthesized.
USPTO guidelines on Markush Claims
If we see the guideline of the patent office across the world, we will find that Markush practice does not refer to a single rule. For example, USPTO added MPEP 706.03(y) in 2018 to authorizes patent examiners to reject a claim on the basis that it contains an improper listing of alternative elements. The close reading 706.03 (y ) guideline reveals that many limitations on the use of Markush type claiming were imposed in view of the improper Markush Grouping reasoning. For example, claiming a genus expressed as a group consisting of certain specified materials is allowed in chemical cases. This type of claim is employed when there is no commonly accepted generic expression commensurate in scope with the field the applicant desires to cover. Inventions in metallurgy, refractories, ceramics, pharmacy, pharmacology, and biology may be claimed under the Markush formula, but it has consistently been held to be improper to extend it to purely mechanical features or process steps. Using the term “comprising” instead of “consisting of” is improper. Other limitations include:
- “The use of Markush claims of diminishing scope should not, in itself, be considered a sufficient basis for objection to or rejection of claims. However, if such a practice renders the claims indefinite or if it results in undue multiplicity, an appropriate rejection should be made. This practice, with respect to Markush claims of diminishing scope, is being continued.
- The materials set forth in the Markush group ordinarily must belong to a recognised physical or chemical class or to an art-recognized class.
- When the Markush group occurs in a claim reciting a process or a combination (not a single compound), it is sufficient if the members of the group are disclosed in the specification to possess at least one property in common, which is mainly responsible for their function in the claimed relationship, and it is clear from their very nature or from the prior art that all of them possess this property. “
For USPTO examiners, the test for Markush-type claims was applied as liberally as possible; present practice, which holds that claims reciting Markush groups are not generic claims, may subject the groups to a more stringent test for the propriety of the recited members. For example, “Where a Markush expression is applied only to a portion of a chemical compound, the propriety of the grouping is determined by a consideration of the compound as a whole and does not depend on there being a community of properties in the members of the Markush expression.”
In another illustration under MPEP 706.03(y), it is stated that when materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in a conventional manner or alternatively. For example, if “wherein R is a material selected from the group consisting of A, B, C and D” is a proper limitation, then “wherein R is A, B, C or D” shall also be considered proper.” Interestingly, a situation may occur in which a patentee has presented a number of examples which, in the examiner’s opinion, are sufficiently representative to support a generic claim and yet a court may subsequently hold the claim invalid on the ground of undue breadth. In such cases, the patentee is often limited to species claims, which may not provide him with suitable protection. This highlights the pitfalls of claiming improper Markush group. In US Patent applications in the life sciences, with claims in the “Markush” format, may be subjected to “improper Markush grouping” rejections. However, if the applicant proves that the alternatives of the Markush grouping share a single structural similarity and a common use, then such objection would be withdrawn.
Position in India
In India, the practice relating to the allowability/restriction of Markush claims is more or less following USPTO practice. In Astrazeneca Ab & Anr. vs Intas Pharmaceuticals Limited Delhi High Court, in the decision on 20 July 2021 dwells on the reach of Markush claim in Indian Patent No.205147(*147) and Indian Patent No.235625 (*625) in an infringement dispute.
Facts of the case
This case arises out of nine appeals relating to two impugn the orders/judgments of denial of interim relief, in suits instituted by the appellants/plaintiffs, i.e. (i) AstraZeneca AB, Sweden and (ii) AstraZeneca Pharma India Ltd. against the respondent(s)/defendant(s) in each of the appeals, for permanent injunction restraining infringement of patent and for ancillary reliefs. Application to restrain the respondent(s)/defendant(s) from manufacturing, selling, or otherwise dealing in any manner whatsoever, the product comprising the compound ‘Dapagliflozin’ (‘DAPA’), which was the subject matter of Indian Patent No.205147 (‘IN 147’) and Indian Patent No.235625 (‘IN 625’).
The court issued two orders in a gap of 16 days, with both, independently of each other, on the same facts, concluding that the appellants/plaintiffs, during the pendency of the suits for a permanent injunction to restrain infringement of patent, are not entitled to any interim injunction restraining respondent(s)/defendant(s) from manufacturing and selling the pharmaceutical products which are alleged to be in breach of the patent of the appellants/plaintiffs. The court gave many reasons for denying the interim injunction to the appellant, but for this discussion, we are limiting the reasons given by the appeal court relating to Markush practice in India and the allowability of selection patent within Markush claims.
Applicability of Markush claims
In this case, the appeal court discussed and analysed Markush claiming practice in detail and observed that:
“33. “Markush”, in In Re: Harnisch 631 F. 2d 716 (of the United States Court of Customs and Patent Appeals), has been explained as under:
“”Markush” was the name of an applicant for patent (Eugene A. Markush) who happened to use in a claim a type of definition *720 of a genus or subgenus by enumeration of species, which he did not devise and which had been used before in patent claims. The examiner considered the claim to be “alternative” in form, objected to it, and Markush petitioned the Commissioner. Assistant Commissioner Kinnan, in Ex parte Markush, 1925 CD 126 (Com.Pat. 1924), approved the form of claim and granted the petition, thus requiring the examiner to examine it for patentability. Thus, the name “Markush” became attached to a type of claim expression, and that is all it connotes.”
After looking at the origin and purpose of Markush claim, the court went on to elucidate that:
“34. The words ‘Markush’, ‘Genus’, ‘Species’, do not find mention in the Patents Act. We thus proceeded to examine, whether in the Indian statutory regime, what the counsel for the appellants/plaintiffs has argued, is permissible i.e. of a patent being first granted of “a core structure” and/or of a formula, only “generally describing the molecules, rather than detailing each and every molecule covered by the formula” and thereafter a second patent being granted detailing each and every molecule. The counsel for the appellants/plaintiffs referred to Section 10(5) in this regard.”
Coverage and disclosure: Novartis effect
Reacting to the contention of the respondent/defendant that “the appellants/plaintiffs, in their pleadings, had admitted that DAPA was covered in IN 147 and that there was no distinction between coverage and disclosure, as held in Novartis supra, IN 625 was invalid, having been disclosed in IN 147″, the appeal court observed that
“(P) however a reading of Novartis supra showed that the Supreme Court clearly noted the distinction between coverage and disclosure; thus it would have to be determined on the facts of each case, whether the species patent was merely covered by the Markush claim or was disclosed in the same;
(Q) that applying the test laid down in Novartis supra to the facts of the present suits, it was evident that in the claims specifications of IN 147, the composition of DAPA was not mentioned and only the general properties of Markush claim with various permutations and combinations were mentioned;”
Further, the appellants/plaintiffs also did not apply for drug approval based on IN 147 and applied for drug approval based on IN 625, and based on these findings, the court ruled that
“(S) that on a prima facie view of the matter, it could not be said that DAPA was disclosed in IN 147;
(T) that IN 625 was also prima facie not liable to be revoked on the ground of prior claiming; “
Selection Patent within Markush Allowed
Reacting to the argument of the defendant on what should constitute as prior art in this case, the appeal court observed that
“to constitute prior disclosure of an invention, the matter relied upon as prior art must disclose subject matter which, if performed, would necessarily result in infringement of the patent;” .
Speaking on the allowability of the Markush formula with a number of variables, the appeal court observed: “(I) that Markush formula with number of variables can be granted a valid patent“. Thus, there is no statutory bar on patent claims having a Markush formula with multiple alternatives. Relating to the allowability of selection patents within the Markush structure, the appeal court categorically observed that
“(J) that a selection patent, which though covered under the Markush formula, is not disclosed clearly and unambiguously in the Markush formula, can also be granted a valid patent;”
(K) that a selection patent must show substantial advantage or avoidance of disadvantage by use of the selected members of the species patent, as compared to the non-selected members of the genus patent;
Applying Novartis case
The appeal court applied the ruling of the Novartis case to the following contention and counter arguments-
“(L) that it is the case of the appellants/plaintiffs, that the pharmaceutical composition of DAPA was not arrived at, much less manufactured or marketed pursuant to IN 147 and the pharmaceutical composition of DAPA specifically disclosed in IN 625 clearly showed a substantial advantage and hence it could not be held that DAPA was disclosed in IN 147;
(M) that it was the case of the appellants/plaintiffs, that though IN 147 covered DAPA, however, it nowhere disclosed DAPA and the same was specifically disclosed in IN 625 and that IN 147 disclosed only 80 exemplified compounds and DAPA was not one amongst these 80 compounds;
(N) however, according to the respondent(s)/defendant(s), example 12 of IN 147 disclosed the compound claimed in IN 625; it was further the case of the respondent(s)/defendant(s), that example 12 of IN 147 gave five methods of preparation–the appellants/plaintiffs rebutted the said arguments by contending that in example 12 of IN 147, all the procedures relate to methoxy substitution and not to ethoxy and that in the entire example 12 of IN 147, there was no teaching in favour of ethoxy–from a reading of claims in IN 147 and in IN 625, it was clear that IN 147 comprised of a group of claims belonging to a family and even the closest example in IN 147 disclosed methoxy benzophenone as the ingredient of the compound and there was no disclosure of a compound with the ethoxy group, as in DAPA;”
and noted the distinction between coverage and disclosure, as stated in the Novartis case, and observed that
“(P) however, a reading of Novartis supra showed that the Supreme Court clearly noted the distinction between coverage and disclosure; thus it would have to be determined on the facts of each case, whether the species patent was merely covered by the Markush claim or was disclosed in the same;”.
The appeal court applied the test laid down in Novartis supra to the facts of the present suits and ruled that “it was evident that in the claims specifications of IN 147, the composition of DAPA was not mentioned and only the general properties of Markush claim with various permutations and combinations were mentioned; “
The Appeal Court also observed that the appellants/plaintiffs also did not apply for drug approval based on IN 147 and applied for drug approval based on IN 625. Therefore, on a prima facie view of the matter, it could not be said that DAPA was disclosed in IN 147, and IN 625 was also prima facie not liable to be revoked on the ground of prior claims.
Conclusion
The Astrazeneca case is a classic example of how the Markush claims would be interpreted by the Indian courts for the purpose of infringement analysis and for the arguments relating to the revocation of a patent based on prior claiming. The rationale behind allowing Markush formula with multiple variants is a longstanding practice based on the fact that there is a certain degree of predictability in chemistry, and certain substitutions at various sites of a relatively complex core molecular structure can be predicted to result in a molecule that retains the utility of other molecules in the genus that have been synthesised and tested. This makes it easy for the applicant to cover the maximum number of predictable results without synthesising them all. The Markush claim writing practice is here to stay in the Indian patent practice like in the USA. The USPTO guidelines on Markush Claims are quite exhaustive as compared to India Guidelines. If we see in the Novartis AG case, we will find that the claims at issue were found invalid under Section 3(d) requirement of enhanced efficacy. This decision clearly left open the possibility of patent protection for a selection invention that satisfies the Section 3(d) standard. This clearly matches what the court observed in the AstraZeneca case, which is that a selection patent, which, though covered under the Markush formula, is not disclosed clearly and unambiguously in the Markush formula, can also be granted a valid patent. However, an expert opinion on the reach and limits of the Markush claims will be helpful to reap the maximum coverage and protection of a patent.