API and IP Newsletter
Contents
FDA approvals in March 2023
We follow FDA approvals of small molecules and discuss chemistry and related IP aspects in our Newsletter.
In March 2023, Neuren Pharmaceuticals received approval for Trofinetide (DAYBUE) oral solution. It is a medication used for the treatment of Rett syndrome.
Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age and almost exclusively in females. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often have slower growth, difficulty walking, and a smaller head size.
Synthesis of Trofinetide is disclosed in Tetrahedron Volume 61, Issue 42, 17 October 2005, Pages 10018-10035 (on page 100028 Trofinetide synthesis is reported)
In Tetrahedron publication, Trofinetide is reported as an hygroscopic colourless solid. MP 144.80C.
RBC Capital Markets analyst Gregory Renza, predicted peak U.S. sales of Trofinetide
to exceed $500 million by 2032 for Neuren Pharmaceuticals.
FDA label reports, Trofinetide is a white to off-white solid and is freely soluble in water. DAYBUE (Brand name of Trofinetide) is a pink to red, oral solution with each 5 mL containing 1 g of trofinetide (200 mg/mL).
The oral solution also contains FD&C Red No. 40, maltitol, methylparaben sodium, propylparaben sodium, purified water, strawberry flavor, and sucralose as inactive ingredients.
The current methods of producing compositions containing trofinetide are allegedly difficult to scale to commercial quantities.
To address this problem, Neuren Pharmaceuticals identified new compositions and manufacturing methods in which the compound trofinetide is made using silylation technology.
Use of this new strategy allegedly provides for new compositions and substantially larger quantities of trofinetide can be produced. This could be commercial formulation of Neuren Pharmaceuticals. This is covered in patent family WO2021026066A1 filed by Neuren in 2020.
Jubilant Biosys is importing methyl proline in small quantities, which is RM for Trofinetide. There could be possibility that Jubilant has started API development in laboratory.
General information
Novel method for analyzing protein crystals could open up new avenues for drug discovery
Protein crystallography produces bright spots, known as Bragg peaks, from the crystals, providing high-resolution information about the shape and structure of a protein. This process also captures blurry images—patterns and clouds related to the movement and vibrations of the proteins—hidden in the background of the Bragg peaks.
News here.
UCI researchers discover new drugs with potential for treating leading causes of blindness in age-related and inherited retinal diseases
In a University of California, Irvine-led study,1 a team of researchers recently discovered small-molecule drugs with potential clinical utility in the treatment of age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP).
News here
Intellectual Property
What is broadening of the claims of a granted patent? And how European Patent Office (EPO) prohibits it?
In EPO practice Art. 123(3) EPC is aimed at protecting the interests of third parties by prohibiting any broadening of the claims of a granted patent. Such a broadening of claim is not possible even if there is a basis for such broadening in the application as filed.
In short, the European patent application or European patent cannot be amended in such a way that it contains subject-matter which extends beyond the content of the application as filed.
Let us understand this broadening of claim with one example in one of the recent decisions by EPO
This example is about patent EP 2453743 titled N-Acetyl Cysteine Compositions and Their Use In Improving The Therapeutic Efficacy of Acetaminophen
This patent was issued to Leland Stanford Junior University. This patent was opposed by Prüfer & Partner mbB.
Claim 1 of the main request reads as follows (emphasis added by the board; strikethrough and bold text representing deletion and addition respectively compared with claim 1 as granted):
"1. [deleted: A composition] An oral formulation for use in a method of treating pain in a subject in need of analgesic relief, [deleted: the composition comprising an oral formulation] comprising:
(a) a unit dose of acetaminophen and
(b) a therapeutic efficacy-enhancing amount of N-acetylcysteine;
wherein a total of all unit doses to be administrated per day according to said method is an amount less than a standard maximum daily dose of acetaminophen, wherein the standard maximum daily dose of acetaminophen is:
200 mg for a subject 0-3 months of age, 2.72-4.99 kg (6-11 lb) body weight, receiving 40 mg/dose;
400 mg for a subject 4-11 months of age, 5.44-7.71 kg (12-17 lb) body weight, receiving 80 mg/dose;
600 mg for a subject 12-23 months of age, 8.16-10.43 kg (18-23 lb) body weight, receiving 120 mg/dose;
800 mg for a subject 2-3 years of age, 10.89-15.85 kg (24-35 lb) body weight, receiving 160 mg/dose;
1200 mg for a subject 4-5 years of age, 16.33-21.32 kg (36-47 lb) body weight, receiving 240 mg/dose;
1600 mg for a subject 6-8 years of age, 21.77-26.76 kg (48-59 lb) body weight, receiving 320 mg/dose;
[deleted: 1625 mg for a subject 6-11 years of age, receiving 325 mg/dose;]
2000 mg for a subject 9-10 years of age, 27.22-32.21 kg (60-71 lb) body weight, receiving 400 mg/dose;
2400 mg for a subject 11 years of age, 32.66-43.09 kg (72-95 lb) body weight, receiving 480 mg/dose;
3200 mg for a subject 12 years of age, 43.55 kg (96 lb) body weight receiving 640 mg/dose;
[deleted: 4000 mg for a subject >12 years of age to adult, receiving 650 mg/dose;]
4000 mg for a subject >12 years of age to adult, receiving 500 mg/dose;
wherein the N-acetylcysteine supplements the analgesic activity of the acetaminophen in the formulation such that a lower dose of acetaminophen can be used to achieve the same therapeutic effect as would be achieved with a higher dose of unsupplemented acetaminophen, and wherein:
(i) acetaminophen and N-acetylcysteine are present in the formulation in a molar ratio of acetaminophen to N-acetylcysteine ranging from 1:15 to 1:0.000977; and
(ii) the formulation is effective to provide pain relief equivalent to said standard maximum daily dose of acetaminophen when administered alone."
The deletions of two exemplified embodiments, which were previously required in claim 1 as granted for certain categories of subjects to be treated, meant that these subjects could be treated with a higher maximum daily dose than that stated in claim 1 as granted.
This resulted in an extension of scope of the claimed subject-matter, contrary to the requirements of Article 123(3) EPC.
Claim 1 of the main request has thus been amended, when compared with claim 1 as granted, by inter alia deleting two standard maximum daily doses with the related patient group ("1625 mg for a subject 6-11 years of age, receiving 325 mg/dose" and "4000 mg for a subject >12 years of age to adult, receiving 650 mg/dose").
The deletion of the standard maximum daily dose of 1625 mg with respect to subjects 6-11 years of age receiving a 325 mg/dose, in claim 1, implies that the standard maximum daily dose for these subjects may be more than 1625 mg. The standard maximum daily dose for these subjects is however limited to 1625 mg in claim 1 as granted. The above deletion thus results in an extension of scope of the claimed subject-matter.
The same extension applies for the deletion of the standard maximum daily dose of 4000 mg with respect to subjects >12 years of age to adult receiving 650 mg/dose.
The patentee submitted that the deletion of a standard maximum daily dose together with the corresponding patient group from the list of claim 1 as granted excluded the treatment of this patient group and thus limited the scope of the claimed subject-matter.
The board did not agree. The board said, if the patentee’s logic was correct, deleting all the standard maximum daily doses and patient groups of claim 1 as granted would imply that the scope of claim 1 would be reduced to zero. Claim 1 in such a situation, however, would be worded as an ordinary second medical use claim without any patient group being defined. It cannot be correct that such a claim has a scope that is reduced to zero. Therefore the patentee’s submission must fail.
For these reasons, claim 1 does not meet the requirements of Article 123(3) EPC. The amended claim is not allowable.
Decision Here
