API and IP Newsletter
Contents
FDA approvals: 505 (b) (2) approvals in July 2024
We follow ANDA approvals and 505 (b) (2) approvals every month. In last month, ie in July 2024 there are about 8 applicants sought approvals via 505 (b) (2) route.
More details are in below table.
General information
Big Pharma Cuts R&D, Sending Shudders Through Industry
The pandemic led to massive increases in research and development among pharmaceutical companies as they raced to discover vaccines and treatments for Covid-19. But those days are over, and many pharma companies are looking to cut costs as they contend with a slowdown.
News here
Galera Therapeutics settles lawsuit for $975,000
The legal dispute, which centered on allegations of contract breach and negligence, was resolved with the payment and mutual releases, effectively terminating the existing contracts between the parties.
News here
Intellectual Property
Aragon Vs Generics UK – Apalutamide Form B
European Patent EP 2858985 was issued to Aragon Pharmaceuticals, Inc. and Sloan-Kettering Institute for Cancer Research (Aragon).
It was opposed by Sagittarius Intellectual Property LLP, Generics (U.K.) Limited and Luigi, Rumi (Patent attorney).
At the first instance, EPO upheld the patent. Two of the opponents at first instance viz Sagittarius Intellectual Property LLP, Generics (U.K.) Limited appealed the decision.
To the appellate board (Boards of Appeal at EPO), Sagittarius Intellectual Property LLP, Generics (U.K.) Limited (Generics UK) requested that the decision under appeal be set aside, and that the patent be revoked in its entirety.
The respondent (ie Aragon who is the patentee) requested dismissal of the appeal and maintenance of the patent as granted.
Following prior art documents cited
Claim 1 which was contested reads as follows:
"A crystalline Form B of apalutamide that is characterized as having at least one of:
(a) an X-Ray powder diffraction (XRPD) pattern the same as shown in Figure 2;
(b) an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 12.1 0.1 2-Theta, 16.0 0.1 2- Theta, 16.7 0.1 2-Theta, 20.1 0.1 2-Theta, 20.3 0.1 2-Theta;
(c) unit cell parameters equal to the following at -173 C:
(d) the same X-ray powder diffraction (XRPD) pattern as (a) or (b) post storage at 40 C and 75% RH for at least a week; or
(e) the same X-ray powder diffraction (XRPD) pattern as (a) or (b) post storage at 25 C and 92% RH for 12 days".
We will discuss inventive step.
Inventive step - Article 100(a) and 56 EPC
The claim 1 of the main request relates to crystalline Form B of apalutamide.
Both appellants (Sagittarius and Generic UK) and the respondents (Aragon ) agreed that D1 represented the closest prior art, while appellant II (ie Generic UK) also submitted that claim 1 lacked inventive step over D2 as closest prior art.
Distinguishing features
D1 (WO 2007/126765 A2) discloses the preparation of apalutamide as compound A52 on page 28 (scheme at the top of the page). The physical form of the apalutamide product prepared is not provided (page 28, lines 10-12).
In experimental report D3, Sagittarius reworked the preparation of apalutamide according to D1 and obtained a solid which when analysed by XRPD was revealed as amorphous. Since this conclusion was not disputed by the respondents (Aragon), it is accepted that apalutamide prepared according to D1 is amorphous.
Patent document D2 discloses the preparation of apalutamide and its recrystallisation from DCM/EtOH (paragraph [0091]). There is no information in D2 nor has any evidence been provided by any of the parties as to the specific form of the crystalline material prepared according to D2.
Claim 1 of the main request is therefore distinguished from both D1 and D2 in that a specific crystalline form of apalutamide denoted Form B is provided, while D1 discloses the amorphous form and D2 discloses an undefined crystalline form.
The patent proprietor ie the respondents (Aragon) argued that the advantageous effects of Form B
less hygroscopic,
highly thermodynamically stable and
highly polymorphically stable.
Obviousness
The appellants' (Sagittarius and Generic UK) arguments on obviousness were not specifically directed to the obviousness of the solution to the objective technical problem as formulated above, namely the provision of a form of apalutamide with a beneficial combination of properties.
Sagittarius submitted that in view of the fact that apalutamide was the subject of an Investigational New Drug (IND) filing before the filing date of the patent as evidenced by D10, the skilled person would have been motivated to perform routine polymorphic analyses or screening. In particular, the skilled person would commence such analyses in the knowledge that apalutamide was at a development stage suitable for stage 2 clinical trials. Such analyses were known to the skilled person from common general knowledge represented by, for example, D4, D6, D8 and D27, and hence would have been carried out by the skilled person on apalutamide. Following such routine guidance, the skilled person would have arrived at the claimed Form B in an obvious manner.
The board disagreed. The board said, the appellants' (Sagittarius and Generic UK) submissions fail to take into account the formulation of the objective technical problem set out above in accordance with the problem-solution approach.
Specifically, as stated by the patentee Aragon, (the respondents), Form B displays a beneficial combination of properties as set out above which cannot have been expected by the mere provision of a crystalline form per se.
Sagittarius and Generic UK also relied on the old decision T 41/17 to support the argument that Form B was obvious. Specifically, in T 41/17 the board stated that the skilled person looking for a stable crystalline form of sorafenib tosylate would have screened for thermodynamically most stable form. The appellants Sagittarius and Generic UK argued on this basis that the same applied in the present case, and the skilled person would inevitably arrive at the claimed subject-matter.
The board disagreed. As stated by Aragon (the patentee), in T 41/17, the claimed crystalline form was alleged to have the advantage that it did not convert to other forms during mechanical stress.
The technical problem was defined as the provision of a stable form suitable for the preparation of a pharmaceutical tablet, and the solutions was considered obvious because the skilled person would have performed a screening to identify the most thermodynamically stable form, which was also expected not to convert to other forms under mechanical stress. Hence, the provision of thermodynamically most stable form was an obvious solution to that specific problem
In the present case in contrast, thermodynamic stability is only one property from the aforementioned beneficial combination of properties displayed by the claimed Form B of apalutamide. Therefore, even if the effect of thermodynamic stability were to have been considered obvious, the same does not apply to the beneficial combination, since, for example, there is no teaching in the prior art that the effect of lower hygroscopicity could be obtained with the thermodynamically most stable form of apalutamide.
Sagittarius submitted that the skilled person, starting from the amorphous apalutamide of D1, would have been in a "try and see" situation. Specifically, the skilled person would have carried out a routine polymorphic screening as addressed above and arrived at Form B as claimed. Sagittarius cited the Case Law of the Boards of Appeal, where the consideration that the skilled person would have adopted a "try and see" attitude was a reason for denying an inventive step. Hence, Sagittarius argued that this situation applies to the present case.
The board disagreed for the reasons provided by Aragon. Specifically, the "try and see" case law cited by the appellant Sagittarius concerns the situation in which the prior art suggested that a clear way forward would solve the technical problem at hand, i.e. an "approach suggested by the prior art", as mentioned in the text of the case law cited by the appellant Sagittarius. Hence, the try-and-see situation is entirely predicated on the existence of a pointer to the solution in the prior art. In the present case, as established above, no pointer in the prior art leads the skilled person confronted with the above-defined objective technical problem to the solution provided by claim 1. Hence, the "try and see" case law is irrelevant in the present situation.
Given the foregoing, the Board concluded that the subject matter of claim 1 of the main request involves an inventive step starting from each of D1 and D2.
The patent was upheld.
Decision here
