Patentability of Brain Organoids derived from iPSC– A Legal Evaluation with Interdisciplinary Aspects

Abstract

Brain Organoids in their current state of development are patentable. Future brain organoids may face some challenges in this regard, which I address in this contribution. Brain organoids unproblematically fulfil the general prerequisites of patentability set forth in Art. 3 (1) EU-Directive 98/44/EC (invention, novelty, inventive step and susceptibility of industrial application). Patentability is excluded if an invention makes use of human embryos or constitutes a stage of the human body in the individual phases of its formation and development. Both do not apply to brain organoids, unless ES-cells are used. Art. 6 (1) EU-Directive 98/44/EC excludes patentability for inventions “the commercial exploitation of which would be contrary to ordre public or morality”. While there is no conceivable scenario, in which the commercial application of current brain organoids violates the ordre public, the same is not necessarily true for future brain organoids. Keeping in mind that a development of consciousness-like abilities in future brain organoids cannot be excluded and that an ability for both physical and psychological suffering has been theorized, both of which are aspects of the ordre public, certain applications of future brain organoids may constitute a violation of the ordre public and therefore lead to an exclusion of patentability.

Scientific Background

Brain organoids were first successfully generated from pluripotent stem cells [1, 2]¹ in 2013 by a group of researchers led by Madeline Lancaster [3]. They mimic the development of human brains in vivo, including the processes of neurogenesis. Brain organoids are severely limited in size² [4,5,6] and do not form all cell types of the human brain [7]. Although there seems to be no limit to developmental possibilities, scientists agree that current organoids are still far away [8, 9]³ from the formation of consciousness [8, 10,11,12,13].

Nonetheless, brain organoids, depending on their concrete make-up, offer a plethora of possibilities, e.g. for understanding neurogenesis in vivo, researching neurodegenerative diseases, which are challenging or impossible to study in vivo [3, 13, 14,15,16,17], clinical trials of drugs on human tissue [18, 19]⁴ and determining the appropriate drug therapy on the patient’s own tissue.⁵ The declared long-term goal is to replace damaged brain tissue with such artificially produced brain tissue [9, 20].

Legal Framework

Purpose of Patent Law and Patenting as Such

Patents grant inventors the right to exclusively exploit their inventions economically for a certain period of time.⁶ The specific rights conferred by a patent depend on the patent legislation in each specific country, cf. Art. 64 European Patent Convention a fortiori. The idea of such protection of the inventor is based on considerations of reward, ownership, incentive and disclosure. It is based on the assumption that an inventor is more motivated to gain new knowledge and share it with the general public if they can expect to receive something in return.⁷

Applicable Regulations

The regulatory system for biotechnological inventions is complex. The German Patent Act⁸ (PatG) applicable at national (German) level is supplemented on the European level by the Convention on the Grant of European Patents⁹ (European Patent Convention – EPC), the Implementing Regulations to the EPC¹⁰ (IR-EPC) and the EU Biopatent Directive¹¹ (Biopatent Directive). The Biopatent Directive, among other things, served to harmonise patent law in the individual member states. This means that the different national patent laws are (or should be) essentially identical in content and effect.¹² Where the law contains indeterminate legal terms, their interpretation depends on the landscape of values prevalent in each member state.¹³ The provisions on the patentability of biotechnological inventions specified in Art. 2–6 Biopatent Directive are reflected in Secs. 1a, 2 and 2a PatG¹⁴ and, almost verbatim, also in Rules 26 to 34 IR-EPC. Additionally, the Biopatent Directive must be consulted for European patent applications relating to biotechnological inventions.¹⁵

Generally, patentability (the possibility for exclusive economic exploitation) and the legality of research activities in a certain field are unrelated and the existence of a patent does not prohibit research, cf. Sec. 11 No. 2, 2b PatG. Non-patentability and a prohibition of research, may, however, in some instances hinge on the same legal criteria or be considered to be wrong based on the same moral considerations, i.e. where the use of (parts of) the human body or human embryos is concerned. Both will be covered in more detail below.

General Prerequisites of Patentability

Sec. 1(1) PatG, Art. 3(1) BioPat Directive and Art. 52(1) EPC determine the general prerequisites of patentability. Accordingly, technological inventions are patentable if they are new, involve an inventive step and are susceptible to industrial application.

Brain organoids made from human induced pluripotent stem cells (hiPSCs) are technological inventions. Furthermore, in the field of brain organoids inventions can be expected to be new for the foreseeable future. Additionally, brain organoids themselves, as well as the processes and protocols for their production, fulfil the requirements of an inventive step. Finally, brain organoids and the processes for their production are already susceptible to industrial application where research purposes are concerned. With an increasing use of brain organoids in the future, e.g. in therapy, their production may be necessary on an industrial scale.¹⁶ Brain organoids and the processes for their production fulfil the general prerequisites of patentability.¹⁷ First patents on brain organoids have already been granted.¹⁸

Grounds for Exclusion of Patentability

Secs. 1a(1), 2(1), (2)(1) PatG, Art. 5(1), 6 Biopatent Directive, 53 lit. a EPC and Rules 28(1) lit. a.-d., 29(1) IR-EPC contain specific exclusions to patentability. No patents are granted for the human body at the various stages of its formation and development (including the use of embryos) and for inventions, the commercial exploitation of which would be contrary to ordre public or morality.¹⁹ The interpretation of these grounds for exclusion is primarily based on ethical considerations.²⁰

As isolated brains models without the potential to develop into complete human beings, brain organoids do not fall under the exclusion of patentability for the human body. As their generation does not require the use of human embryos and they cannot develop into human beings, patentability is not excluded for these reasons.

Hoewever, Sec. 2(1) PatG, Art. 6(1) Biopatent Directive and Art. 53(a) EPC, also referred to in Rule 28 IR-EPC, open patent law to general ordre public considerations. Inventions “the commercial exploitation of which would be contrary to ordre public or morality”, whereby such a violation does not already result from the fact that the exploitation “is prohibited by law or regulation”, are therefore non-patentable. The examples of exclusionary criteria (“in particular”) mentioned in Sec. 2(2) PatG, Art. 6(2) Biopatent Directive and Rule 28(1) IR-EPC restrict the broad concept of ordre public²¹ and guide possible additional criteria in both scope and content. Only such aspects are included in the considerations, which are relevant in the respective field of law.

Since the ordre-public considerations are complex. They warrant a closer look to understand their scope and the consequences of their application.

Content of the concept of ordre public in patent law

Secs. 2(2) PatG and Sec. 6(2) BioPat Directive expressly exclude patentability for inventions which use clearly and widely disapproved methods (cloning, germline interventions, commercial and industrial use of embryos and processes for modifying the genetic identity of animals, which cause disproportionate suffering). While the general part of the provisions allows for the consideration of relevant but not specifically named infringements and introduces certain ethical standards into patent law, the specific examples serve to concretise the general ordre public clauses in Sec. 2(1) PatG, Art. 6(1) BioPat Directive and Art. 53(a) EPC.

The examples given in Sec. 2(2) PatG, Art. 6(2) Biopatent Directive and Rule 28(1)(a)-(d) IR-EPC all represent aspects of human dignity. For cloning, particular reference is made to the “creation of a human being as spare parts or the use of the human body for the production of goods”.²² Non-patentability in the case of germ line interventions serve to avoid the unforeseeable consequences of such an intervention for the immediately affected and also for future generations and to protect the germ line, which is regarded as particularly important philosophically, ethically and religiously.²³ Embryos are protected in this context because they are, even at a very early stage, human life.²⁴ All these points also include aspects of protection against objectification of human life.²⁵

Art. 6(2)(d) Biopatent Directive²⁶ establishes references to animal protection, the criteria of capacity for suffering and to the protection of consciousness and conscious entities by degree, hence changing with varying degrees of consciousness. These and some other aspects will be discussed in more detail below regarding their applicability to the patentability of brain organoids and the question of whether an infringement of these aspects is sufficient to cause a violation of the ordre public, which is in turn sufficient for an exclusion of patentability.

Consequences of ordre public-based non-patentability

If the commercial exploitation of an invention is contrary to ordre public or morality, this leads to an exclusion of patentability.²⁷ In accordance with the general aims of patenting, the non-patentability due to a violation of the ordre public does not prevent the (commercial) exploitation of an invention as such, but only the grant of a patent guaranteeing the owner exclusive commercial use.²⁸ The fact that a violation of the ordre public may be theoretically possible is not sufficient for a refusal of the patent.²⁹ However, uses contrary to the ordre public may be excluded from the patent, which would lead to the patent protection not covering such aspects.³⁰

Indications of possible conflicts with the ordre public do not come to mind regarding current brain organoids, which are similar to other tissue and should therefore not be treated differently [21,22,23,24].

Previous Court Decisions on the Interpretation of the Directive

There are several landmark rulings of the ECJ on the interpretation of individual provisions of the Biopatent Directive, which are briefly discussed below with regard to the aspects relevant here. The decisions also provide the basis for a necessary re-evaluation with regard to more complex brain organoids. The rulings, insofar as relevant there, dealt with hESCs, not hiPSCs. Nevertheless, the Court’s considerations in the judgments can give an impression of how the individual patent exclusions are to be interpreted.

In C-377/98 (Netherlands./. Parliament and Council) the Court found that patenting isolated components of the human body does not violate human dignity. It stated that human dignity is sufficiently protected by Art. 5(1) Biopatent Directive,³¹ since Art. 6(2) of the Biopatent Directive is non-exhaustive (as required by recital 38) and therefore all conceivable processes contrary to human dignity are excluded from patentability.³²

In C-34/10 (Brüstle./. Greenpeace) the Court stressed that the capacity to commence the process of the development of a human being is prerequisite for something to be an “embryo” within the meaning of Art. 6(2) Biopatent Directive.³³ Additionally, the Court extended the scope of non-patentability to practically all inventions that required the use of embryonic stem cell lines for their production, because their generation requires the destruction of human embryos.³⁴

It refined the definition in C-364/13 (ISCO./. Comptroller General of Patents), where it added that an organism requires the “inherent capacity” to develop into a human being to constitute an “embryo”.³⁵

Re-evaluation for Future Brain Organoids?

Current brain organoids are generally patentable.³⁶ This situation could change fundamentally if more complex brain organoids are created in the future. While it can be expected that such more complex brain organoids still fulfil the general prerequisites of patentability, there are changes regarding the exclusionary criteria.

Grounds for Exclusion of Patentability

There is no reason to assume that the use of human embryos will become necessary for the production of brain organoids in the future. Furthermore, even more complex brain organoids would not have the intrinsic, inherent ability to develop into a complete human being. Even if brain organoids were able to develop into a fully formed human brain, which is not to be expected in the foreseeable future, such a brain would still not be a complete human being. It would thus not fulfil the criteria set by the ECJ in its Brüstle and ISCO-decisions.³⁷

Similarly, there is no change with regard to the criterion of the use of the human body. Even if brain organoids were used to replace destroyed brain tissue [9, 20], this would not change. As with other (patented) medical prostheses, the patent effect does not extend to the human body into which they are transplanted.

The production of human-animal chimeras might lead to an exclusion under Sec. 2(2)(4) PatG, Art. 6(2)(d) Biopatent Directive, Art. 53(a) EPC and Rule 28(1)(d) IR-EPC if it would result in a change in the genetic identity of the animals and cause suffering to the animals that outweighs the medical benefit. For the required assessment, the EPO has developed the so-called balancing approach, which enables a weighing of the relevant aspects.³⁸

Exclusion of Patentability of Future Brain Prganoids Due to Ordre Public Considerations?

However, ordre public considerations warrant a more comprehensive need for re-evaluation.

Subject of the following considerations are future, necessarily hypothetical, brain organoids, which are able to develop more sophisticated cognitive abilities. Although they are already seriously discussed in ethics and law, they are, so far, only possible on paper. Such hypothetical considerations can help to anticipate possible problematic scenarios in the future and help to find a solution before they come about.

Possible criterion for protection: Moral status

Moral status can be defined as the basic position of an entity in the normative cosmos. It is by concept very general and is usually conferred on a certain ‘category’ of entities such as children or animals.³⁹ Different ethical concepts are pursued for the attribution of moral status. The “epistemological approach” assumes that the mere fact that an entity is subject of moral considerations can be an indication of a corresponding status (epistemological significance).⁴⁰ The “theoretical approach” identifies certain properties from ethical considerations to attach moral status (theoretical significance). The relationship between both approaches is notoriously undecided, especially since they have a certain interrelation.⁴¹

The theoretical approach raises questions regarding which properties are decisive for granting moral status and whether they are intrinsic or extrinsic. An example of an extrinsic property is that an object is to be considered morally, if it is owned by a human being (whose moral status is assumed) and therefore has value to the human being. However, it remains doubtful whether such extrinsic properties actually confer moral status on the object itself or whether the treatment of the object does not rather result only from the status and rights granted to the human being.⁴² The possibility of granting moral status because an entity can be the object of a one-sided relationship established by a human being [25] is also not convincing: moral status that does not result from the object itself, but only from its relationship to an entity that already has it, is arbitrary and can quickly disappear.

It follows, therefore, that the intrinsic properties on which moral status is measured must be identified. A gradual attribution of status can also be considered. Lower or higher status is then reflected in the rights and consideration of the interests of the entity.⁴³ In doing so, a gradation that questions the generality of the status should be avoided.⁴⁴ Possible criteria suggested for granting moral status, which I discuss in detail below, are humanness (aa), different forms of consciousness (bb) and other sophisticated psychological and cognitive abilities (dd). The use of consciousness as a criterion would require its quantifiability (cc).

aa) Humanness

One criterion proposed to be sufficient and necessary for granting moral status is being human.⁴⁵ It has been argued that, although they are clearly not fully-fledged humans, future brain organoids grown from human iPSCs endowed with consciousness could be “a new type of entity belonging to the human species” [25], although they would certainly have a very different life experience than humans. It is, however, highly dubitable whether humanness should also be considered when assessing possible ordre public violations. From an ethical perspective, this reduction of moral status to humanity has been criticised as “speciesism” [26]. Furthermore, since human bodies are already excepted from patentability, it seems unnecessary to introduce moral status as an additional criterion to then exhaust it in the criterion of humanness.

Additionally, from a legal perspective it would undermine a legislative decision. After all, the human body is already protected under Sec. 1a(1) PatG and Art. 5(1) Biopatent Directive. Brain organoids do not fall under this ground for exclusion. Humanness as a value is so close to both human dignity and human bodies that there is no interpretational room to use it as an unwritten ordre public exclusion.

bb) Consciousness

The criterion proposed most often for granting moral status to brain organoids is consciousness. After all, since humans experience the world through consciousness and perceive this to be one of the defining and outstanding features, it is not far-fetched to attribute value to it.

There is no universally agreed definition of consciousness. Rather, it is a term which describes a wide variety of mental phenomena [27]. The core of consciousness, however, seems to be a subjective experience.⁴⁶

Being conscious can be used to describe a property that an entity generally has or does not have. It can also be used to describe mental states. In this case, an entity capable of accessing conscious states is conscious when it is in a conscious state. An entity generally capable of conscious states is not conscious when it is comatose or asleep [28].

Consciousness exists in different forms and to different extents. I will discuss those which are most relevant regarding moral status.

i. Phenomenal Consciousness

Phenomenal consciousness is considered the core concept of consciousness by many authors. Nevertheless, it is considered practically impossible to define phenomenal consciousness [29,30,31]. It is understood to be the kind of consciousness that describes that something is always like or feels like doing or experiencing something (what-it-is-like-ness) [30,31,32] as opposed to introspective access consciousness [29, 33]. It is often assumed that people without phenomenal consciousness would be zombies, i.e. they would be able to perceive things but would not associate these perceptions with a feeling [30, 31].

This is to be distinguished from the characteristic of personhood, which requires cognitive capacities such as autonomy, rationality, emotionality, moral freedom of decision or highly developed self-awareness [13].⁴⁷ Unlike simple consciousness, personhood, in addition to the above criteria, requires interaction with the environment, including living and participating in society.⁴⁸

Because brain organoids lack the ability to develop into a complete human being, they could only fulfil the prerequisites of personhood if they acquire the ability to process input and output of information, if necessary by connecting different organoids or by generating human-animal chimeras. Phenomenal consciousness, on the other hand, which is subject to fewer preconditions, could appear earlier, as soon as perception becomes possible.

ii. Access Consciousness

Access consciousness is the ability to have access to information, i.e. to be able to access the content of information [29, 30]. An external state is access conscious if its contents can be reported; if the state is not access conscious, its contents cannot be reported.⁴⁹ Therefore, access consciousness is also described as an information processing concept [30].

With regard to its occurrence in brain organoids, the same conditions apply as for an occurrence of phenomenal consciousness.

iii. Self-consciousness

Self-consciousness comprises the idea that there is a “self” and that one can use this idea as soon as one thinks about oneself [29, 34]. From the existence of self-awareness can follow, for example, the interest in pursuing a pleasure, avoiding pain, fulfilling a desire and seeking the beautiful in life [29, 31]. Such an ability has so far only been attributed to humans and some primates [29].⁵⁰

Lesser forms of self-consciousness, so called pre-reflective consciousness have been suggested by some [35, 36]. However, because they do not require the entity to be able to reflect on its own consciousness or be aware of its own awareness, it is argued that the inner life they experience is not as “rich” as that of truly self-conscious entities, wherefore they cannot be attributed moral status.

It can so far be ruled out that brain organoids can reach this level of consciousness.

cc) (Not yet) an option for determination: Quantifiability of consciousness

If brain organoids were able to attain one of the above described states of consciousness, which, as has just been described, is not yet the case and will likely not be the case in the foreseeable future, their commercial exploitation might well be contrary to ordre public considerations. However, even if brain organoids were able to reach a relevant state of consciousness, their doing so would still need to be proven in order to be able to attach moral status to it. One way to do so would be to measure and quantify it.⁵¹ At present, there is no reliable method for determining consciousness, which does not depend on the patient or the entity interacting with its environment [37]. With the possibility of communication missing, conventional methods of assessment fail. This is the case, for example, with anaesthetised or sleeping persons, those in a coma, but also patients who are conscious but unable to communicate through speech or movement due to complete physical paralysis (i.e. locked-in syndrome). The same problem exists with brain organoids. Because they lack the ability to process most sensory input (and to produce output), it is, as yet, impossible to determine whether they are conscious or even only have the ability to perceive. Below, I discuss methods for quantifying consciousness, which, if they were developed further, could solve this problem [10].

i. Integrated Information Theory According to Tononi

The Integrated Information Theory of Consciousness (IIT) attempts to prove the existence of consciousness by means of mathematical calculations. It aims at distinguishing entities (systems) with consciousness from those without. IIT assumes five axioms, “intrinsic existence (my experience exists from my own intrinsic perspective); composition (it has structure), information (it is specific), integration (it is unitary) and exclusion (it is definite)” [38], from which it derives five postulates. According to the IIT, consciousness only exists if all these conditions are fulfilled. The IIT derives a numerical value of consciousness according to the quality and quantity with which the prerequisites are fulfilled [39,40,41]. IIT assumes that even inactive systems (or those that show only very low activity) can have consciousness. This is true in cases in which the respective neurons can have an influence on past or future states and thus in cases in which they are at least ready to react to incoming stimuli. Since IIT takes the five axioms as given and obvious, it can be loosely traced back to the philosophical method of phenomenology.

ii. Perturbational Complexity Index according to Casali et al.

The Perturbational Complexity Index (PCI) developed by Casali et al. indicates the complexity of brain activity. It uses two criteria developed by IIT, but without being strictly dependent on IIT in its result [37]. To determine it, the brain is stimulated by means of transcranial magnetic stimulation (TMS) and the resulting reaction is measured by means of electroencephalography (EEG). From this, a numerical result (between 0 and 1) is calculated. It is reliably able to distinguish unconscious patients from those who are conscious [42] and can even show gradations of consciousness [37]. In intermediate states, the measured values are reliably higher than in the states with loss of consciousness and reliably lower than in the states with consciousness [37].

Although the PCI is based on the basic ideas of IIT, there is no direct connection between the two methods. PCI is suitable for the determination of certain aspects of IIT, which enables better differentiation between subjects with limited and full consciousness [37]. However, the existing EEG technology cannot yet provide the accuracy required by IIT.

While there are advances to measuring brain activity [43] and hopes to measure the PCI for brain organoids [10], it is not clear whether the technical possibilities and the nature of brain organoids would currently allow a sufficiently accurate measurement.

In practice, the theoretical parameters discussed here cannot yet be used to determine the existing level of consciousness and, consequently, the attribution of moral status by degree and the determination of worthiness of protection cannot yet be based thereon. While the use of such parameters could theoretically, if corresponding results were available, contribute to quantifying consciousness and, on this basis, to introducing it into the balancing approach and to drawing conclusions about patentability. However, the technical possibilities and the characteristics of currently available brain organoids do not yet allow for such a procedure.⁵²

dd) Relevance of precursors of consciousness

With the quantification of consciousness unavailable as a method for determining the necessity to protect and grant moral status to brain organoids, other options must be considered.

As stated earlier, it is intuitive to attribute value to consciousness. Whether good or bad, sensory input still leaves a subjective experience, which in itself has value [44,45,46,47]. However, the arguments for these criteria rely heavily on an appeal to our own experience, which we perceive as valuable [44, 46, 47]. The case for consciousness as a criterion is built on intuition.⁵³ The core of why brain organoids specifically raise so many concerns and moral questions is that what we value about ourselves might exist in these organoids. However, a lot of proposed criteria exist in beings we do not afford any (higher) moral status to: many animals possess phenomenal consciousness (and some possibly more) with much more certainty than brain organoids will for the foreseeable future. An orientation for brain organoid regulation along the lines of animal protection could therefore be helpful.⁵⁴

It is recognised that current brain organoids are far from developing any form of consciousness. It is also widely accepted that the emergence of consciousness in brain organoids cannot be ruled out in the future as development progresses [8, 10, 13, 43, 48,49,50,51]. Biologically, trends to further increase the complexity of brain organoids are discernible [23, 51,52,53,54,55]. At the latest with the appearance of consciousness and its precursors, the questions of status described above will become relevant. In this the context, a necessity for general dignity considerations and, more specifically, human dignity considerations will arise. The possibility of an attribution of status by degree means that not every indication of consciousness automatically leads to an exclusion of patentability. Instead, under the so-called balancing approach developed by the EPO, the benefit of the invention (i.e. a substantial medical benefit) on the one hand and the suffering caused to the entity (which is higher in further developed entities) on the other hand are weighed against each other.⁵⁵ Because “higher” entities, due to their further developed capabilities, have a higher aptitude for suffering, they are afforded greater protection. If an entity develops to be more complex or acquires new abilities, it may be necessary to increase the protection granted to this entity. In this vein, according to the balancing approach, the same use may be permissible for one entity, but not for another, further developed entity. Therefore, if the benefit of the invention included in the balancing does not increase to the same extent as the (further) development of any existing consciousness, i.e. if the protection to be granted increases, but the medical benefit which it is weighed against does not, the possibility arises that at some point the scales tip to the detriment of the invention, because the balance with the ordre public can no longer be struck.

i. Capacity to Experience Pleasure and Pain

A possible decisive criterion for moral status is whether an entity can experience pleasure and pain and whether it can suffer. After all, pleasure and pain are intrinsically good or bad for the entity experiencing it. Thus, the action causing pleasure is morally good and – more importantly – it is morally bad to cause pain and suffering.⁵⁶

The infliction of pain and suffering on a human can constitute a violation of their human dignity.⁵⁷ Pain and suffering also play an important role in general ordre public considerations.⁵⁸ Additionally, as discussed above, unnecessary suffering caused in changing the genetic identity of animals is an express reason for the exclusion of patentability.⁵⁹ This indicates that the capacity to experience suffering is relevant in the context of patentability.

In brain organoids, a capacity to experience pain and suffering could simply depend on whether it fulfils the anatomical prerequisites. Because the human brain does not have pain receptors, brain organoids are not susceptible to pain. Those are contained in the meninges, which current brain organoids do not develop. However, pain and suffering can also be caused psychologically [13], which cannot be excluded, albeit also not proven, for brain organoids.

This criterion is deeply connected to consciousness. If an entity experiences pain and suffering and perceives it to be aversive, this makes the experience of the entity intrinsically bad.⁶⁰ Several proponents of consciousness as a marker of moral status reason that an entity can have experience and perceive something to be a certain way only if it is conscious [13, 29, 56]. Therefore, without such conscious experience, pain and suffering inflicted but not experienced as such, is irrelevant. Hence, because this also requires an evaluation of the consciousness of the entity, it meets the same practical difficulties I discussed above with regard to the quantifiability of consciousness.

ii. Having Interests

Another possible criterion for the granting of moral status is having interests. This presupposes consciousness as well, as only a conscious entity can have subjectively good or bad experiences to strive for or avoid. It has even been stated that having interests is the reason for moral significance being attributed to consciousness in the first place [31]. Consciousness on its own is not sufficient to have interests. Rather additional physical and cognitive circumstances must exist, which lend valence to the experience [31].

These interests must be considered morally.⁶¹ Their complexity affects their weight in the consideration: to feed is an interest easier satisfied than the one to be a successful opera singer. Therefore, the more complex the interests are, the more sophisticated the claim for the additional protection of interest becomes.⁶² Entities which can one day be reasonably expected to have interests should also be considered, though they are not yet attributed moral status.⁶³

The thought that one should try to consider all interests involved and secure those with rights has some merit. One problem is, however, that humans can articulate their own interests but can only infer the interests which other species or organoids might have. Additionally, while it is sensible to consider possible interests when allotting rights, the very individualist approach goes against the principle of equality, upon which our justice system is founded.

Human dignity, consideration of parallel stages of human development

Since moral status itself depends on fulfilling certain criteria, which in turn are discussed as criteria for worthiness of protection, the existence of moral status is not itself suitable as a criterion for worthiness of protection. Rather, granting moral status is an indication of the existence of the criteria for worthiness of protection and runs parallel to the assumption of worthiness of protection. The criteria discussed in the debate on the attribution of moral status correspond to the criteria already mentioned above. For these, too, it must therefore be shown that they are essentially based on aspects of (human) dignity and are therefore suitable for influencing ordre public considerations.

Human dignity is the “supreme constitutional value”.⁶⁴ As a central principle of the applicable values and the basis of what constitutes the generally recognised landscape of values, it is also part of the ordre public.⁶⁵ If human dignity is included in the assessment of patentability as a unifying basis for the above-mentioned criteria of worthiness of protection,⁶⁶ it is also appropriate to draw parallels to relevant milestones in human development as soon as brain organoids are able to reach these developmental stages. This also guarantees a uniform application of the law [23]. Potential for consciousness as well as for pain and stress perception, for example, can be considered as relevant milestones. The ability to perceive physical pain and a capacity for sensation together determine an individual’s ability to suffer.

Suffering can be both physical and psychological. For children, isolation or neglect is considered a violation child welfare.⁶⁷ Child welfare itself is a “specific adaptation of human dignity”.⁶⁸ Because brain organoids cannot process most sensory input and cannot communicate with the outside world, some authors discuss the possibility of them suffering from sensory deprivation.⁶⁹ Ultimately, for the above discussed reasons, it is, as yet, not possible to determine whether this is the case.⁷⁰

Relevant reference points in human development can therefore be the emergence of the predispositions for pain processing and later the actual ability to perceive pain. Also relevant is the ability to perceive, which gradually increases to become consciousness.

Interim Conclusion

It is to be expected that some of the aspects described above will apply to further developed, more complex brain organoids in the future. These aspects, which can essentially be traced back to considerations of dignity, depending on the intensity of their occurrence, can lead to problems with the ordre public. If not only one, but the only conceivable use is contrary to the ordre public in this sense, or if this is the case for a use explicitly mentioned in the patent application, non-patentability may result. With increasing biotechnological progress, this consequence becomes more likely.

Cases not in Breach of the Ordre Public

Even occurrences that do not reach the quality of an ordre public infringement can influence the public debate, which in turn can influence the general opinion on the (political) handling of such issues and can influence or might damage this scientific field for years.⁷¹ Even points that do not exclude patentability may therefore entail a legal prohibition or at least an obstacle to the commercial exploitation of an invention. The debate about “mini-brains”, which can possibly achieve states similar to consciousness, is fundamentally capable of provoking such a reaction [8, 57, 58].

This finding can equally be transferred to dealing with considerations of dignity aspects, so that interferences by inventions that lie below the ordre public threshold, now even detached from the industrial use that is only relevant for patentability, are in principle relevant for the inventors and should be taken into account.

Conclusion

Brain organoids made from hiPSCs are regularly patentable at their current stage of development. In principle, they fulfil the general patentability requirements of “invention”, “novelty”, “inventive step” and “susceptibility of industrial application” according to Sec.1(1)PatG, Art. 52(1) EPC and Art. 3(1) Biopatent Directive. Furthermore, the grounds for exclusion of patentability for the human body in the various stages of its development, Art. 5(1) Biopatent Directive, Sec. 1a(1) PatG and Rule 29(1) IR-EPC and the general provisions on the protection of the ordre public in Art. 6 Biopatent Directive, Sec. 2(1), (2)(1) PatG, Art. 53(a) EPC and Rule 28(1) lit. a.-d. IR-EPC do not prevent the patenting of current brain organoids.

The situation is different for more complex brain organoids with aspects of consciousness or its preliminary stages, or special capabilities such as the ability to process sensory input, which are conceivable as biotechnological progress continues. The ordre public considerations based on human dignity that could then be relevant may be morally explosive in a way that they exclude the patentability of such advanced brain organoids because of the proximity of the capabilities in question to living humans, or “only” to living animals.