API and IP Newsletter
Contents
FDA approvals-Motixafortide
In September 2023, the FDA approved Motixafortide for stem cell mobilization (SCM) in autologous stem cell transplantation (ASCT) in patients with multiple myeloma. Brand name – APHEXDA.
Motixafortide is a peptide, also known as 4F-benzoyl-TN14003 (4-fluoro-benzoyl-Arg-Arg-Nal- Cys-Tyr-Cit-Lys-DLys-Pro-Tyr-Arg-Cit-Cys-Arg-NH2, SEQ ID NO: 1), and is cyclic upon formation of a disulfide bond between the two Cys residues thereof.
US 7,423,007 describes peptides having CXC4 antagonism; including 4F- benzoyl-TN 14003.
According to US 7,423,007, 4F-benzoyl-TN14003 is manufactured by solid phase synthesis using DIPCDI HOBt as a coupling agent, in DMF (with amino acids added at 2.5 equivalents), followed by deprotection and cleavage using 1 M TMSBr- thioanisole/TFA with m-cresol and ethanedithiol, and cyclization by air oxidation.
Additional background art includes US 7,138,488 and US 8,435,939, and International Patent Application Publications WO 2008/075369, WO 2008/075370, WO 2010/146578, WO 2012/095849 and WO 2013/160895 (PCT applications); and U.S. Provisional Patent Application No. 62/938,962.
These US patents and US equivalents of PCT applications would be listed in Organge Book.
APHEXDA is supplied as a sterile white to off-white, preservative-free lyophilized powder in single-dose vials. Each vial contains 73 mg of motixafortide (provided as motixafortide acetate) for reconstitution with 2 mL 0.45% saline, delivering 62 mg motixafortide per 1.7 mL. Motixafortide is present as a salt with 4 to 8.5 molar equivalents of acetate.
Many companies who are active in peptide chemistry could be developing generic Motixafortide. For example Lupin is importing Fmoc-Arg(Pbf)-OH. Fmoc-Arg(Pbf)-OH is the standard form for the introduction of Arg in the Fmoc strategy of solid phase peptide synthesis (SPPS). Auro Peptides, Cadila are also importing these compounds. However, these types of compounds are commonly used in peptide chemistry. The side-chain protecting group Pbf is good for the guanidinium group in arginine and can be easily removed with TFA.
Hence one cannot claim with reasonable certainly that these companies (Lupin, Auro, Cadila) are working only on motixafortide but chances are very high looking at timing of their imports.
General information
Nycaa Vs Oykaa
The Delhi High Court has restrained owner of an online website selling makeup and skincare products from using the mark “Oykaa” or any other mark similar or identical to Nycaa
News here.
The current situation with SPCs is a mess
As a European patent attorney at Sanofi, Brigitte Carion-Taravella has decades of experience in patent prosecution and in-house IP rights management. Next week, she will participate in a panel discussion at the AIPPI on life sciences and EU supplementary protection certificates. In an exclusive interview, she explains how the harmonisation of SPC decisions could improve the use of IP rights for pharmaceutical companies.
News here
Intellectual Property
Nova Chemicals (International) S.A. Vs Sasol South Africa Limited
This decision concerns the appeals filed by the patent proprietor (Nova Chemicals (International) S.A.) and opponent (Sasol South Africa Limited ) against the opposition division's interlocutory decision at European Patent Office.
Patent: EP2935163B1 (Continuous ethylene tetramerization process)
Patentee: Nova Chemicals (International) S.A.
Opponent: Sasol South Africa Limited
In its notice of opposition, Sasol South Africa Limited had requested that the patent be revoked in its entirety based, inter alia, on the grounds for opposition under Article 100(a) EPC in combination with Article 56 EPC (lack of inventive step) and Article 100(c) EPC (added subject-matter).
In this write-up we will cover inventive step arguments. I liked this decision very much. Many time Board of Appeal decisions at EPO are worth studying. Very methodical approach by the Board of Appeals.
In the obviousness decision, you would notice generally The Board would follow following steps
The Board first discusses what is prior art
Second, patent claims (including auxiliary requests, obviously we are not covering discussions about all auxiliary requests in this write-up)
decides what would be the closest prior art among list of prior art documents.
identifies technical feature in the impugned patent which is distinguishing feature from the prior art.
Confirms objective technical problem solved by the alleged invention.
Ensures whether distinguishing technical feature is solving the objective technical problem.
Finally, opines either in favor of the inventive step (obviousness) if technical effect is achieved and the distinguishing feature of the invention solves objective technical problem or decides otherwise.
Prior art
The following documents submitted by the parties are relevant to the decision:
D1 S. Kuhlmann, "Selective Tri- and Tetramerization of Ethylene - from Ligand Design to Mini-Plant Operation", Dissertation, Erlangen 2006
D3 WO 2007/007272 A2 (Here)
D4 R. Walsh et al., Applied Catalysis A: General, 306 (2006) 184-191
Claims
Claim 1 of the main request (claims as granted) reads as follows:
"A continuous flow process for the oligomerization of ethylene, said process comprising
I) adding ethylene and solvent to a mixed reactor and contacting said ethylene under oligomerization conditions with a catalyst system comprising
1) a diphosphine ligand defined by the formula (R1)(R2)-P1-bridge-P2(R3)(R4) wherein R1, R2, R3 and R4 are independently selected from the group consisting of hydrocarbyl and heterohydrocarbyl and the bridge is a moiety that is bonded to both phosphorus atoms;
2) a source of Cr; and
3) an activator
II) removing a product discharge stream comprising hexene, octene, C10+ oligomers and solvent from said reactor; and
III) controlling the flow of said solvent to said reactor such that the product discharge stream contains from 2 to 25 weight % octene, based on the weight of hexene, octene, C10+ oligomers and solvent; and
wherein said process is further characterized by being conducted at a catalyst concentration of from 0.3 to 5 micromolar Cr."
Claim 11 as granted reads as follows:
"The process of claim 1 wherein step III) also comprises controlling the flow of ethylene to said reactor such that the product discharge stream contains from 2 to 25 weight % octene."
Closest prior art
The document D3 (ie WO 2007/007272 A2; in particular Example 29) was chosen as the closest prior art.
Document D3 is directed to the oligomerisation of ethylene in the presence of chromium catalysts in suitable solvents.
The Board decided, the document D3 is thus a suitable starting point for assessing inventive step.
Earlier the opposition division's decision (the first instance decision) was based on Example 29 of document D3 as the starting point in the problem-solution approach. The board saw no reason to deviate from this.
Distinguishing feature
Whether or not Example 29 of D3 implicitly disclosed an octene concentration in the discharge stream from 2 to 25 weight % was a contentious issue between the parties.
The question of whether this feature is disclosed in D3 can, however, be left unanswered because even if this feature is considered to be a distinguishing feature, the claimed subject-matter is not allowable for lack of inventive step.
The board endorses the opposition division's conclusion that the act of controlling the solvent flow to the reactor cannot be regarded as a further distinguishing feature.
It follows from page 3 of D3 that the solvent flow is purposively controlled, causing a reduction in the formation of olefins with ten or more carbon atoms (C10+ fraction).
Deliberate control of the solvent flow rate also takes place in Example 29 of D3; see lines 12 to 16 on page 42 and line 20 on page 46.
By adjusting the solvent flow rate, the catalyst is purposively diluted to reduce the formation of C10+ products.
In view of the product composition displayed in Table 1, the resulting C10+ fraction amounts to at most 14.5 weight % and is thus comparable to the results featured in Table 2 of the patent.
Hence, Board opined, the opponent's (Sasol South Africa Limited) line of argument that D3 also discloses controlling the solvent flow is convincing.
Technical effect and objective technical problem
No particular effect has been demonstrated to be associated with the range for the octene content in the discharge stream called for in claim 1; the board agrees with the opponent Sasol South Africa Limited that Figure 1 shows the entirety of the product (hexene and octene) formed in the reactor rather than only the octene concentration present in the reactor.
Hence, Figure 1 of the patent supports the conclusion that the amount of C10+ in the discharge stream increases as the amount of product in the discharge stream increases.
The opponent's (Sasol South Africa Limited ) argument that the control of the hexene concentration in the product stream would also be necessary to control the amount of C10+ oligomers formed is valid.
Consequently, the objective technical problem is to provide an alternative process for ethene oligomerisation.
Obviousness
The board agreed with the opponent (Sasol South Africa Limited ) that the skilled person studying document D3 would have been aware of the fact that the concentration of octene in the discharge stream can be controlled, inter alia, by adjusting the solvent flow rate.
Reducing the concentration of octene in the reactor by increasing the solvent flow rate removes the starting compound/octene for the formation of higher oligomers by secondary incorporation (D3, also mentions the formation of secondary products from the primary reaction products).
Hence, the Board conclude that the concentration of octene in the product stream formed can, inter alia, be controlled/adjusted (to values such as from 2 to 25 weight %) by the residence time and concentration (adjusted by the solvent flow rate) of the reactants in the reactor in an obvious way.
Decision: Patent is revoked.
Decision here
