In a recent judgment, the Delhi High Court upheld the Ld. Controller’s decision refusing a patent application for not being patentable subject matter as amounting to ‘discovery’ under Section 3(c) of the Indian Patents Act, 1970 (‘Act’) and for failing to meet the requirements of sufficiency under Sections 10(4) and 10(5) of the Act.
Background of the case
The subject patent application was IN201717005699 by THE REGENTS OF THE UNIVERSITY OF CALIFORNIA titled ‘VACCINE FOR LIVESTOCK PRODUCTION SYSTEMS’ filed at the IPO on 17 February 2017, for which a hearing notice was issued on 22 November 2021. The Controller’s refusal on the written submission by the Applicant, filed on 7 December 2021, was for a total number of five amended claims, of which amended claims 1 to 4 were drawn towards a recombinant Salmonella microorganism, and the amended claim 5 was directed to a vaccine composition having the recombinant Salmonella for inducing an immune response in a subject.
The refused claim 1 was as follows:
“A recombinant Salmonella microorganism, wherein said microorganism comprises a loss of function mutation in the dam gene and at least one further sifA, spvB and mgtC in a gene selected from the group consisting of: sifA, spvB and mgtC wherein the microorganism is a Salmonella enterica subsp. Enterica serovar selected from the group consisting of S. Typhimurium, S. Enteritidis, S. Dublin, S. Newport, S. Choleraesuis, and S. Bovismorbificans”.
Decision
At the outset, let’s take a look at the points analysed by the Hon’ble Court in this judgement. The Court assessed:
- if the claims 1 to 5 have been sufficiently disclosed as required under Section 10(4) and 10(5) of the Act; and
- if claims 1 and 2 constitute non-patentable subject matter under Section 3(c) of the Act.
Insufficiency
As regards the objection under Section 10(4) and 10(5) of the Act, the High Court in view of the requirements under these provisions, analysed the subject application in the light of the complete specification and the amended claim. Particularly, the requirement of sufficiency of disclosure was analysed under Section 10(4) of the Act and the extent or scope of the claims was analysed under Section 10(5) of the Act.
From the Patent Office’s refusal order (‘impugned order’) of the subject application, it is revealed that the refusal was based on the assertion that the claims 1-5 do not satisfy Section 10(4) and 10(5) of the Act as it lacks support, clarity, disclosure and definiteness over the entire scope of claimed subject matter. At the outset, the reasoning relied by the Patent Office was incorrect, as it failed to rely on the breadth of the claim scope for assessing sufficiency. Merely because the claimed subject matter is considered as having a range of possibilities does not ipso facto render it insufficient. If such a stance is taken, Markush claims would never cross the sufficiency threshold.
In the claim, the recombinant Salmonella is defined as one having a loss of function mutation in the dam gene, in addition to a loss of function mutation in at least one of sifA, spvB or mgtC genes. Particularly, the invention relates to double mutants of Salmonella for use as vaccines. In refusing the amended claims, the impugned order incorrectly asserted that innumerable permutation and combinations are possible, and therefore, the complete specification lacks adequate support for the full extent of the claims. For this too, the Patent Office incorrectly equated breadth in claim scope as being an indication for insufficiency. It is pertinent to note that for biotech inventions (as opposed to other technological inventions), due regard has to be given to core aspects of the claimed technology. In the present case too, due regard had to be given as genes of closely related species or sub-species are essentially similar. Therefore, if there is teaching for one species or sub-species, considering the similarity in genetic structure, a ‘person skilled in the art’ would expect, without conducting any undue experimentation, the teaching to equally apply for related species and sub-species. This would only be applicable if there are no other unique differentiating aspects that are present (which was not the case in the present application).
In examining if there was sufficient disclosure, the Hon’ble Court analysed the relevant extracts of the specification, and the subject matter claimed. The Court reasoned that the claims of the subject patent application covered and encompassed various types of loss of function mutations in selected genes of Salmonella microorganisms. The Court also acknowledged that the detailed description further specified the relevance of these genetic mutations. However, as per the Court, the detailed description clarified that the target genes do not necessarily need to be deliberately mutated if the expression of the native gene product is functionally disrupted in some way. As per the Court, this broadens the scope of the subject patent application to include any method of gene disruption, not limited to deliberate genetic modifications. The Court also observed that the detailed description ought to ensure that the subject patent application does not cover naturally mutated Salmonella microorganism, which is excluded under Section 3(c) of the Act.
It is important to note that this reasoning side steps to not only the technical aspects but also to the manner in which sufficiency may be ascertained. For example, based on the reading of the detailed description of the impugned application, it is clear that gene disruptions involving the specific genes identified in the claim will always be deliberate. It is unclear as to why this aspect was not submitted by the Appellant and brought to the attention of the Court. Secondly, the requirement under Section 10(4) and (5) only requires that the invention be sufficiently disclosed such that persons skilled in the art are able to work the claimed invention, without any undue experimentation. Therefore, unless it is shown that the claimed invention is unable to be worked by a person skilled in the art based on the description in the specification, sufficiency is established. Besides the arguments pertaining to the deliberate versus natural mutations, it is unclear as to why the standard of undue experimentation was not pursued by the Appellant.
The specification in the examples provides sufficient details on construction of S. Typhimurium vaccine candidates. It discloses vaccine candidates prepared by introducing an in-frame 300 bp deletion of defined dam sequence (termed damA232) to obtain a parent S. Typhimurium UK-1 damA232 strain which is then engineered to introduce the second deletion mutations to obtain the double mutant candidates dam mgtC, dam sifA, and dam spvB.
With respect to the requirements under Section 10(4)(a) and 10(4)(b) of the Act, the Court held that the complete specification does not fully disclose the inventive contribution to cover insertion and substitution mutations, an aspect which is covered under amended claim 1 and specifically recited in amended claim 2. The Court held that the lack of specific disclosures in respect of insertion and substitution mutations results in an insufficiency of disclosure, which renders the subject patent application non-compliant with the mandatory requirements under Section 10(4)(a) of the Act.
In this context, it is stated that in biotechnology, it is well-understood that a loss-of-function mutation is a genetic change that reduces or eliminates the normal function of a gene or protein. However, the claimed invention was not for mutating or effecting the genetic change, but lies in identifying the genes in specific organisms that can be mutated to reduce or eliminate the normal function of the said genes. Such mutations can be brought about by any mechanism – as long as the genes are mutated to alter the normal function of said genes, the object of the claimed subject matter is achieved. The inventive concept therefore lies in this identification of the genes in the specific organisms that results in the reduction or elimination of the normal function of the said genes. It is again reiterated that the inventive concept is not dependent on the mode of mutation, that is, whether the mutation is by deletion, insertion or substitution, but in the identification of genes that can be mutated. At the risk of oversimplification, an example to explain this is, any disruption in the series of crucial steps or key ingredients of baking a cake, will result in a bad cake. This is irrespective of whether the disruption is by way of adding more or adding less ingredients or by performing the crucial steps for a longer duration or shorter duration or not at all.
In the light of the above, even if the specification does not exemplify construction of double mutants by insertion or substitution mutations, considering the common general knowledge available in the field, would a person skilled in the art in practising the invention be faced with a burden of undue experimentation? It appears that these aspects were not agitated before the Court. The Judgment does not analyze this aspect, and it is not clear if the Bench was made aware of the common general knowledge in relation to loss-of-function mutation. Without such analysis, the conclusion that the complete specification is not sufficiently disclosed may not be entirely justified.
As regards the objection on Section 10(5), the Court by referring to AGFA NV & Anr. v. The Assistant Ld. Controller of Patents and Designs & Anr, and Novartis AG v. Union of India and Ors, analysed clarity and scope of the claimed subject matter.
Section 10(5) of the act requires that,
“the claim or claims of a complete specification …., shall be clear and succinct and shall be fairly based on the matter disclosed in the specification.”
In this regard, the Appellant’s contention that the claim only covers seven combinations of loss of function mutations for each organism, thus for six organisms, the total combinations would be limited to 42 combinations (7 x 6, where 7 is the number of combination and 6 is the number of Salmonella subspecies referred in claim 1), failed before the Controller as missing out to consider the possibilities arising out of the types of mutations. The Hon’ble Court affirmed the Ld. Controller’s findings that the loss of function mutation consisting of an insertion, deletion and/ or substitution of one or more nucleotides results in numerous permutations and combinations in the organisms. The Court held that “the claim fails to provide a clear and precise definition of the full scope of recombinant Salmonella organisms…”, and “claiming of insertion and substitution mutation cannot be considered to be fairly based on the subject matter disclosed in the specification…”, and hence the claims do not meet the requirement of Section 10(4)(c) and 10(5) of the Act.
The Court held that the claims of the subject patent application fail to provide a clear and precise definition of the full scope of recombinant Salmonella organisms covered in the subject patent application, even after a conjoint reading of the claims and the complete specification. Moreover, the claiming of insertion and substitution mutation will not be considered to be fairly based on the subject matter disclosed in the specification, on account of the absence of detailed support or working embodiments demonstrating these mutations. It is not clear from whose perspective the above understanding stems. If this is from the perspective of the ‘person skilled in the art’, there must be some basis to suggest that on reading the claims and specification, the scope is unclear or not discernible to such person skilled in the art.
With regard to the 6 sub-species, it is unclear if arguments and considerations were made on the aspect of conservation of genes across the subspecies. Notably, this aspect was not considered by the Court as well. It is known to a person skilled in the art that gene sequences are highly conserved across subspecies, and hence an argument can be made that double mutations in the specified genes would have similar effect across all the 6 subspecies. A simple search for sequence homology of the specified genes in the subspecies would reveal that these are conserved genes, and hence exemplification in one subspecies should be sufficient to enable a person skilled in the art to practice the invention across the other subspecies as well.
Further, considering the absence of sufficient disclosure under Section 10(4)(a) and 10(4)(b) as determined by the Court, and the lack of public availability of the claimed recombinant Salmonella microorganism, the Applicant’s failure to deposit the claimed microorganism was held as being non-compliant with the requirements under Section 10(4), particularly 10(4)(d)(ii), of the Act. It appears that this objection is consequential to the refusal under Section 10(4)(a) and 10(4)(b), as a deposit of the biological material with an International Depository Authority (IDA) under the Budapest Treaty is only required if the biological material mentioned is not described in the complete specification in such a way as to satisfy clauses (a) and (b) of Section 10(4) of the Act; and if the said biological material is not available to the public.
Non-patentability u/s Section 3(c)
Further, the High Court’s reasoning to adjudicate that the claimed subject matter was ‘discovery’ under Section 3 (c) of the Act, leaves room for discussion. The Court, in its judgment, analyses the aspect of patentability of the claimed subject matter under Section 3(c) in conjunction with the objections under Section 10(4) and 10(5) of the Act.
Section 3(c) of the Act excludes “…discovery of any living thing or non-living substance occurring in nature…”.
Considering that the claimed recombinant Salmonella is a living thing, should a recombinant Salmonella having mutations deliberately introduced by human intervention be considered as “discovery of a living thing”?
The basis of this refusal under Section 3(c) in the impugned order is that the claims are very broad and wide and cover any naturally occurring Salmonella with a loss of function mutation in the dam gene and at least one further loss of function mutation in a gene selected from the group consisting of: sifA, spvB and mgtC.
At the outset, the refusal order fails to provide any evidentiary basis to support this rejection. It is unclear as to how the Ld. Controller concluded that the recombinant Salmonella may be naturally occurring. In such instance, the burden of proof that the claimed recombinant Salmonella exists in nature, rests on the Ld. Controller. In the absence of such proof, the Applicant is left with no proper direction on providing a befitting rebuttal.
The Delhi HC, in this regard, by referring to the disclosure made in the complete specification, held that the subject patent application is so broad that it covers naturally occurring mutations, i.e. endogenous mutations, as well. Hence, it appears that the decision on Section 3(c) is:
- irrespective of the fact that the mutations were introduced by human intervention; and
- based on the assumption that the double mutants with loss of function of dam gene and sifA/spvB/mgtC gene may occurs in nature.
The judgment further states that “unless the subject patent application has been sufficiently disclosed with enabling disclosure and with clear claims, there shall be a serious prejudice that the endogenous mutations claimed in the subject patent application could cover those present naturally and would consequently be non-patentable under Section 3(c) of the Act.”, which is unclear.
The above position and reasoning of the Delhi High Court may potentially render unpatentable, any recombinant micro-organism. Although very remote, there may always be a possibility that a claim on a recombinant version could potentially cover naturally occurring organisms, given the dynamic nature of naturally evolving microbes and that somewhere in the world these microbes may naturally exist. Therefore, an inquiry under Section 3(c), ought to essentially involve a factual determination whether such an organism ‘occurring in nature’. However, without actual evidence or material to suggest such naturally occurring micro-organisms exist, precluding an invention involving recombinant micro-organism as discovery under Section (c) of the Act, on a mere surmise and conjecture, is not justified.
If we were to base the applicability of Section 3(c) on the assumption that endogenous mutations may exist naturally, it is not clear as to how any mutated microorganism can be patentable even if the claim clearly define the specific mutation. In other words, there is no certainty that limiting the claim to deletion mutations would bring the Applicant’s claim outside the scope of Section 3(c), for there may still be double mutants having such deletion mutations irrespective of the clarity of claims. This brings us to the question of what is the test for applicability of Section 3(c)?
The Controller has acknowledged the Novelty of the invention. Hence, meeting the requirement of Novelty under the Act should be sufficient to bring the subject matter outside the scope of Section 3(c) of the Act.
Now, considering the aspect of human intervention, would the expression ‘recombinant’ in the claim be sufficient to overcome Section 3(c) of the Act? The Appellant in this case introduced the expression ‘recombinant’ in response to the objection under Section 3(c) of the Act. The expression ‘recombinant’, in general, refers to ‘genetically engineered’, and clearly indicates presence of human intervention in creation of the microorganism. An argument that a substance created with human intervention does not fall within the scope of Section 3(c), may also find support in Health Protection Agency v. The Ld. Controller General of Patents and another. Hence, surely a recombinant organism cannot be considered as a discovery. The Hon’ble Court, however, has not considered these factors in adjudicating this instant case.
Conclusion
While the judgment leaves certain questions unanswered in the minds of a reader, particularly with respect to the applicability of Section 3(c) of the Act, it can be said that there was scope for certain arguments that could have been made and considered. Notably, the corresponding EP and US applications were granted. Considering that naturally occurring substances are not patentable in US as well, it appears unfair that the Applicant has faced rejection in India for similar subject matter granted by the USPTO.
[The authors are Executive Director and Principal Associate, respectively, in IPR practice at Lakshmikumaran & Sridharan Attorneys]
