API and IP Newsletter

 Contents

• DMF filed by Indian companies in April 2022

• General information

• Five companies personalizing treatments with 3D printed drugs

• How can the pharma industry navigate issues in the global supply chain to minimise drug shortages?

• Intellectual Property

• T 2342/19 (Liquid formulation of AMG 416/AMGEN) of 21.6.2022

DMF filed by Indian companies in April 2022

We analyse DMFs filed by Indian companies. In April, about 50 DMFs were filed and out of which more than 60% were filed by Indian companies. Optimus was top among Indian DMF filers. 

Some of our observations/comments are as below.

HOLDER	SUBJECT	Sidvim comments
OPTIMUS DRUGS PRIVATE LTD	LINAGLIPTIN	More than two dozen DMFs filed. There are Gx approvals in US. But Gx launch one has to wait for some time. In India innovator obtained ad interim injunction order against generic launches.
METROCHEM API PRIVATE LTD	BILASTINE	Two other DMFs filed. Bilastine is currently approved in more than 120 countries and achieved more than ~ $290 million in worldwide sales in 2020. It is not yet approved by FDA. If approved by the FDA, Bilastine would be the first New Chemical Entity antihistamine approved in the US since 2007.
IOL CHEMICALS AND PHARMACEUTICALS LTD	GABAPENTIN USP	Very competitive market, about 20 other active DMFs
OPTIMUS DRUGS PRIVATE LTD	BRIVARACETAM	Volume could be low here, mainly used for epilepsy in children, 12 other DMFs are active, this could be very competitive market.
OPTIMUS DRUGS PRIVATE LTD	VONOPRAZAN FUMARATE	This is interesting, FDA has approved two vonoprazan-based treatments for Helicobacter pylori infection in May 2022 and Optimus filed DMF in April 2022!  Drug was approved first in Japan in 2015 and hence innovator samples were available.

General information

Five companies personalizing treatments with 3D printed drugs

Additive manufacturing, or 3D printing, is a tool that can allow for small-scale production of medicines. This approach uses 3D modeling software to build an object layer-by-layer; for solid drugs, the 3D printer stacks ink with an excipient — inactive substances in drugs added for specific functions like improved stability and bioavailability — and the active pharmaceutical ingredient to print out a finished product. By adjusting the printing parameters, the drug dosages, drug combinations, release profiles and even flavors can be personalized. 

Aprecia Pharmaceuticals

FabRx

Merck

Triastek, Inc.

GlaxoSmithKline

News here.

How can the pharma industry navigate issues in the global supply chain to minimise drug shortages?

Logistical challenges of getting the right materials in the right place remain two years after the pandemic began, causing significant drug shortages to end-users. Businesses are facing challenges in obtaining raw ingredients for medicines.

Many of the medicines most badly affected by these shortages are generic drugs to treat common conditions such as diabetes and heart disease. A break in the supply chain could have enormous implications for millions of people suffering from these conditions.

News here.

Intellectual Property 

T 2342/19 (Liquid formulation of AMG 416/AMGEN) of 21.6.2022

AMG-416, Etelcalcetide (formerly velcalcetide, trade name Parsabiv) is a calcimimetic drug for the treatment of secondary hyperparathyroidism in patients undergoing hemodialysis.

The European Medicines Agency approved the drug in November 2016.

This Boards of appeal decision is regarding EP 3013318. This was granted on the basis of 15 claims. Patent was issued to Amgen. The independent claims of the patent as granted read as follows:

 

"1. A pharmaceutical formulation comprising AMG 416 in aqueous solution, wherein the formulation has a pH of 2.0 to 5.0."

 

"15. A formulation comprising 2 mg/mL to 20 mg/mL of AMG 416 in aqueous solution, a succinate buffer that maintains the formulation at a pH of about 3.0 to 3.5, and a sufficient concentration of sodium chloride for the formulation to be approximately isotonic."

 

1. An opposition was filed against the patent on the grounds that its subject-matter lacked novelty and inventive step.

2. The opposition division took the decision to reject the opposition.

3. Hexal appealed and this matter was before the Boards of appeal. 

4. D1 (D1: WO 2012/170955 A1) was agreed as the closest prior art. It discloses inter alia the present peptide 

5. The closest embodiments of D1, i.e., examples 1 and 2, do not provide any information regarding the actual formulation of the peptide. In particular, it was undisputed that no information regarding the pH was provided. 

6. According to Hexal, it would be nevertheless implicit that the intravenous injection required formulations in the form of an aqueous solution. Accordingly, the subject-matter of claim 1 differs from the one of D1 in that the formulation of AMG 416 is limited to:

1. an aqueous solution

2. having a pH of 2.0 to 5.0.

7. Amgen submitted, the idea of providing an aqueous solution of an active ingredient may appear obvious to the skilled person willing to provide a ready-to-use solution per se. However, in the present case, the active ingredient is a peptide and the formulation of peptides in aqueous solution is known to possibly be challenging due to stability issues 

8. The closest prior art D1 does further not provide any particular hint towards an aqueous solution of AMG 416.

9. Hexal argued, the skilled person would have arrived at the present pH range by carrying out routine pH stability studies.

10. Board said, prior art documents cited by Hexal do not specifically relate to peptides and also discuss other formulations including solid state formulations and suspensions. A prioritisation of the formulation of peptides as solutions cannot therefore be derived from these documents.

11. Finally the Board said, not only aqueous solutions but also non-aqueous solutions and emulsions constitute alternatives when willing to prepare ready-to-use compositions  The skilled person would not have been particularly motivated to prepare an aqueous solution. Performing pH stability studies would thus not have been obvious, in particular as pH is not the only parameter influencing storage stability.

Patent was upheld, the board concluded, the subject-matter of granted claim 1 involves an inventive step

Here