T 2218/16 - Gene therapy and result to be achieved

 Key points

• Claim 1 is a second medical use claim directed to basically an AAV vector comprising a therapeutic gene for use in a method for treating a motor neuron disorder in a subject. The AAV vector is further specified, as well as the mode of administration. The therapeutic gene is defined as “wherein the therapeutic gene is operably linked to a promoter specific or functional in motor neurons”. The claim further specifies a functional feature described below.
• Novelty over D2 is considered. “Document D2 discloses the same scAAV9 vector, therapeutic genes, motor neuron disorders to be treated ...  including the same mode of administration as referred to in claim 1 ... Document D2 further discloses ubiquitous promoters, like CMV ... which as shown in the patent, are functional in motor neurons too.”
• “It was contested between the parties whether or not document D2 discloses motor neurons transfected by the scAAV9 vector.”
• "The claim inter alia specifies that the administration of these vectors cause "infection of spinal cord motor neurons and expression of the gene in spinal cord motor neurons". Accordingly, the claimed use of the scAAV9 vectors is defined by a functional feature that indicates the desired result to be achieved, namely the transfection of spinal cord motor neurons as a necessary prerequisite to achieve a therapeutic effect. According to the case law, functional features are technical features of the claim (see Case Law, II.A.3.4., II.C.7.2.). As set out above, document D2 does not disclose the transfection of motor neurons. Thus, the "result-to-be-achieved" feature in claim 1 relates to a new technical effect."
• “ document D2 is silent on directly transfecting motor neurons, and relates to the transfection of other target cells that, after secretion of a therapeutic product, have an indirect effect on cells involved in the development of particular diseases, inter alia, SMA. The respondents did not dispute that a scAAV9-based therapy that did not directly transfect motor neurons was not suitable for treating SMA. In these circumstances document D2 provides a non-enabling disclosure for the treatment of SMA. Since for the reasons outlined above, the new mechanism of action creates a new clinical situation, the board concludes that the situation in the present case differs from that underlying the decisions T 433/14 and T 406/06.”
• The claims are found to be novel, inventive, and allowable.

T 2218/16 - 

https://www.epo.org/law-practice/case-law-appeals/recent/t162218eu1.html

Claim 1 of the main request reads:

"1. An AAV vector comprising a therapeutic gene for use in a method for treating a motor neuron disorder in a subject, wherein said AAV vector is administered by by intraperitoneal (i.p.), intramuscular (i.m.) or intravenous (i.v.) injection, preferably intravenous injection, to said subject, said administration causing infection of spinal cord motor neurons and expression of the gene in spinal cord motor neurons, wherein said AAV vector is:

- a double-stranded self-complementary AAV9 vector, or

- a pseudotyped AAV vector comprising a double-stranded self-complementary AAV genome derived from an AAV serotype different from the AAV9 serotype and a capsid derived from an AAV9 capsid; and

wherein the therapeutic gene is operably linked to a promoter specific or functional in motor neurons".

Reasons for the Decision

Novelty

40. In a first line of argument, the appellant submitted that the subject-matter of claim 1 lacked novelty over documents D1 and D2. Since, as the appellant further submitted, the disclosure of both documents is "very similar, if not identical", in the following reference will be made to relevant passages in document D2 only.

40.1 Document D2 discloses the same scAAV9 vector, therapeutic genes, motor neuron disorders to be treated (e.g. SMA, amyotrophic lateral sclerosis (ALS), or Kennedy's disease), including the same mode of administration as referred to in claim 1 (see for example page 1, first paragraph; page 6, lines 1 to 3, 17 to 19; page 12, lines 3 to 10 and 15 to 23). Document D2 further discloses ubiquitous promoters, like CMV (see page 9, lines 17, 27 and 28), which as shown in the patent, are functional in motor neurons too. The board is therefore not convinced by the respondents' argument, that document D2 discloses a promoter subset that is different from the "functional" promoters cited in claim 1.

40.2 It was contested between the parties whether or not document D2 discloses motor neurons transfected by the scAAV9 vector. Example 4 on page 16 of document D2 discloses GFP expression in various brain cells, including neuronal cells in the "enthorhinal cortex", after i.p. and i.m. injections of scAAV9. Document D2 states in the last paragraph on page 16: "GFP expression was further detected in blood vessels throughout the brain and the spinal cord. Unexpectedly, a strong GFP expression was also found in fibres of the corticospinal tract that cross at the cervical spinal cord level (Fig. 3E and 4C). Transduction of these fibres likely results from infection of upper motor neurons whose somas are located in the motor cortex and that also appeared GFP-immunopositive" (emphasis added).

40.3 The board agrees with the opposition division that the passage in document D2 indicated above does not directly and unambiguously disclose that motor neurons are transfected, since the term "likely" implies a probability only that the transfected cells are indeed motor neurons. According to established case law, subject-matter is directly and unambiguously derivable from a prior art document only, if it is "beyond doubt - not merely probable" (see Case Law, I.C.4.1).

40.4 The appellant further submitted that it was irrelevant whether or not document D2 disclosed transfected motor neurons, since the feature "causing infection of spinal cord motor neurons and expression of the gene in spinal cord motor neurons" (i.e. the "result-to-be-achieved" feature) in claim 1 was not a technical feature, but a mere desideratum. Infection of spinal cord motor neurons had to be achieved by the remaining features of the claim, all of which were disclosed in document D2. Therefore document D2 inherently disclosed the "result-to-be-achieved" feature. This case resembled the situations discussed in decisions T 433/14 (reasons 18 and 19) and T 406/06 (reasons 12.3) which both denied novelty of a second medical use claim, because a new technical effect alone did not result in a new clinical situation.

40.5 The board disagrees. Claim 1 is directed to an scAAV9 vector or a pseudotyped scAAV9 vector both comprising a therapeutic gene for use in a method for treating a motor neuron disorder. The claim inter alia specifies that the administration of these vectors cause "infection of spinal cord motor neurons and expression of the gene in spinal cord motor neurons". Accordingly, the claimed use of the scAAV9 vectors is defined by a functional feature that indicates the desired result to be achieved, namely the transfection of spinal cord motor neurons as a necessary prerequisite to achieve a therapeutic effect. According to the case law, functional features are technical features of the claim (see Case Law, II.A.3.4., II.C.7.2.). As set out above, document D2 does not disclose the transfection of motor neurons. Thus, the "result-to-be-achieved" feature in claim 1 relates to a new technical effect.

40.6 The scAAV9 vector-based therapeutic effect in treating motor neuron disorders as described in document D2 results from the transfection of cerebrospinal fluid (CSF) secreting cells, such as epithelial cells of the plexus choroids, and/or the ependyma, and/or a meningeal membrane (see e.g. page 2, lines 17 to 29). From there the vector-encoded therapeutic product is secreted into the CSF, where it acts from the external, i.e. indirectly, on disease-causing cells. Thus, document D2 teaches an indirect therapeutic effect on motor neurons. This is different from the technical effect relied upon in claim 1, i.e. the direct transfection of motor neurons.

40.7 The claimed direct transfection of motor neurons allows, for example, the treatment of disorders where the motor neurons are resistant to externally added therapeutic compounds, for example compounds secreted into the CSF as disclosed in document D2. This in the board's opinion, allows for the treatment of a new subgroup of patients, namely of a patient group that can no longer be treated by the extracellular approach disclosed in document D2, and hence, identifies a new clinical situation (see T 836/01, reasons 8).

40.8 The appellant further argued that the treatment of SMA required that the gene coding for the survival of motor neuron protein (SMN) was located in the cell nucleus of motor neurons and hence, could not be supplemented extracellularly to these cells but required their direct transfection (see document D16, abstract). Since document D2 disclosed the treatment of SMA by using SMN as a therapeutic gene, the document inherently disclosed the transfection of motor neurons, since otherwise document D2 contained a non-enabling disclosure.

40.9 According to established case law, attaining a new technical effect (here: the direct transfection of motor neurons) is a functional technical feature of a claim that refers to a new use of a known substance. If that technical feature has not been previously made available to the public, then the claimed invention is novel, even though the technical effect may have inherently taken place in the course of carrying out what has previously been made available to the public (see G 2/88 and G 6/88, OJ EPO 1993, 93 and 114; Reasons point 9).

40.10 As set out above, document D2 is silent on directly transfecting motor neurons, and relates to the transfection of other target cells that, after secretion of a therapeutic product, have an indirect effect on cells involved in the development of particular diseases, inter alia, SMA. The respondents did not dispute that a scAAV9-based therapy that did not directly transfect motor neurons was not suitable for treating SMA. In these circumstances document D2 provides a non-enabling disclosure for the treatment of SMA. Since for the reasons outlined above, the new mechanism of action creates a new clinical situation, the board concludes that the situation in the present case differs from that underlying the decisions T 433/14 and T 406/06.

40.11 In light of the considerations above, the board concludes that the subject-matter of claim 1 is novel over the disclosure of documents D1 and D2.