API and IP Newsletter

 Contents

• DMF filings in November 2022

• General information

• North America is seeing a hiring boom in pharmaceutical industry ESG roles

• Pharma industry wants Budget to announce incentives for conducting R&D

• Intellectual Property

• T 1133/18 (Sublingual apomorphine/SUNOVION) of 15.12.2021

DMF filings in November 2022

We analyze DMF filings of Indian companies. Couple of weeks ago we analyzed DMF filings in the month of October 2021 and this week we have analyzed DMF filed in the month of November 2022.

About 50 DMFs filed in November and more than 50% of those are from Indian API suppliers. 

Glimpses of our analysis is as below. 

HOLDER	SUBJECT	SIDVIM comments
DR REDDYS LABORATORIES LTD	ERIBULIN MESYLATE	DRL owns IP the process of eribulin, different fractions combined to manufacture eribulin. Earlier DRL filed DMF for one of the fractions, fraction A and now filed DMF for eribulin. This will become generic in 2022, and one could see few DMFs soon. Nevertheless, very complex synthesis, so there might not be too much of competition.
BIOCON LTD	EMPAGLIFLOZIN	Very crowded market, 29 DMFs filed already.
CHROMO LABORATORIES, INDIA PRIVATE LTD	ATAZANAVIR SULFATE USP	Many DMFs, many ANDA filers. But what is interesting, this is fifth DMF in one year filed by Chomo Labs. In 2019 too, they filed 7 DMFs. They filed only 2 in 2020, Covid impact. As per their website, the company has only 30 scientists in development. Only 30 scientists, assuming 50% of those are synthetic chemists and remaining are in analytics, it could be considered as remarkable achievement by Chromo in last 3 years.
MSN LIFE SCIENCES PRIVATE LTD	REGADENOSON	Regadenoson should become Gx in US by October 2022. More than a dozen DMFs filed. There are process and polymorph patents listed in OB, so for the launch, one must circumvent those patents. It is about $660 mio product in US and few companies have received tentative approval. I have not seen TA for MSN, but it could be expected soon.
HETERO LABS LTD	APALUTAMIDE	This is 2018 approval and already 9 DMFs filed. One could see too many players on NCE-1 date!

General information

North America is seeing a hiring boom in pharmaceutical industry ESG roles

North America extended its dominance for environmental, social, and governance (ESG) hiring among pharmaceutical industry companies in the three months ending November.

The number of roles in North America made up 51.2 per cent of total ESG jobs – up from 45.4 per cent in the same quarter last year.

That was followed by Asia-Pacific, which saw a 2.2 year-on-year percentage point change in ESG roles.

News here.

Pharma industry wants Budget to announce incentives for conducting R&D

An increase in the budgetary allocation from the current 1.8 per cent of the GDP to 2.5-3 per cent, as envisaged in the National Health Policy 2017 along with a separate allocation for the bio-pharmaceutical sector R&D is imperative

News here.

Intellectual Property 

T 1133/18 (Sublingual apomorphine/SUNOVION) of 15.12.2021

On 2 September 2021 Sunovion announced that it has entered into an agreement with BIAL in which Sunovion has granted exclusive commercial license rights in Europe for apomorphine sublingual film (APL-130277) here.

Though I could not find data for EU, as per Sunovion website by 2030, it is estimated that 1.2 million people in the U.S. and an estimated 10 million people worldwide will be living with Parkinson’s disease.  GlobalData estimated, Kynmobi will have total sales of $361M by 2029 in the US. Here.

EP 2442650 relates apomorphine sublingual film. This patent was upheld at the first instance. 

Generics (U.K.) Limited and LTS LOHMANN Therapie-Systeme AG appealed the first instance decision. 

EP 2442650 claims which contested before appellate board were as follows, 

1. A pharmaceutical composition in unit dosage form formulated for sublingual administration, wherein said unit dosage form is a film or a strip having a first layer and a second layer, wherein the first layer is acidic and comprises apomorphine particles comprising an acid addition salt of apomorphine and the second layer comprises a pH neutralizing agent.

12. The pharmaceutical composition of any of claims 1-11 for use in the treatment of Parkinson's disease, dyskinesia, akinesia in a mammal afflicted with Parkinson's disease.

13. The pharmaceutical composition of any of claims 1-12 for use in the treatment of sexual dysfunction."

 

The patent was opposed on the grounds that the claimed subject-matter lacked an 1.) inventive step, 2.) was not disclosed in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art, and 3.) extended beyond the content of the application as filed.

 

In this write-up we will discuss only inventive step argument. Following documents are key prior art documents

(2) (WO2006/120412)

(3) (WO98/26763)

(23) (US2004/0204440)

1. Document (3) ie WO98/26763 was considered as the closest prior art.

2. WO98/26763 defines a composition in the form of a film for use in the oral cavity comprising apomorphine or a salt of it.  This composition is to be used in the treatment of Parkinson's disease. Preferred excipients have mucoadhesive properties. When mucoadhesive excipients are used, the composition may have two or more layers. The two examples disclose single layer compositions comprising apomorphine hydrochloride.

3. The difference between the subject-matter of claim 1 and the disclosure of WO98/26763 is the presence of the acid addition salt of apomorphine in the form of apomorphine particles and the addition of a neutralising agent in a second layer of the film or strip.

4. The technical problem may be seen as the provision of an alternative pharmaceutical composition suitable for sublingual administration of apomorphine.

5. The problem has been solved. This has not been contested. It remains to be determined whether the claimed solution is obvious.

6. Generics (U.K.) Limited and LTS (Opponents) have referred to documents (2) ie WO2006/120412 and (23) ie US2004/0204440 as rendering the claimed subject-matter obvious.

7. WO2006/120412 defines a kit comprising, in separate compartments of a container, a component (a) comprising apomorphine or an addition salt of it and an excipient and a component (b) comprising a solution including a pH modifying agent. 

8. Component (a) may be in particulate form, for example in the form of dry powder or dry granules, or in the form of a suspension of powder or granules in an appropriate medium (or in other liquid forms requiring dissolution of apomorphine).

9. The two components are to be mixed together at the time of use, and the resulting formulation is administered immediately after the mixing has been effected. 

10. The system of WO2006/120412 thus differs considerably from the system of WO98/26763. Instead of a flat, foil-, paper- or wafer-like form, a kit consisting of either a first powdery/granular or liquid (suspension of particles or solution) component and a liquid second component and requiring a mixing step immediately prior to use is taught. 

11. A person skilled in the art, aiming to provide an alternative composition starting from the film of document (3) ie WO98/26763, would not have considered singling out one of the technical features of the first component (i.e. the particular form of the active agent), incorporating it into the film or strip of the closest prior art and, furthermore, modifying the second component to be suitable to act as a second portion in the form of a layer of a pharmaceutical composition in the form of a film or strip. 

12. There is no pointer anywhere in the prior art at hand that would have motivated the person skilled in the art to combine and additionally modify the technical features of documents (3) ie WO98/26763 and (2) ie WO2006/120412.

13. Document (23), ie US2004/0204440 relates to the treatment of sexual dysfunction via inhalation therapy (paragraph [0011]). A skilled person would not have considered directly transferring characteristics of a composition formulated for inhalation to a film or strip for sublingual administration.

Consequently, the claimed subject-matter is not obvious when considering the prior art invoked by the appellant ie Generics (U.K.) Limited and LTS. An inventive step is thus acknowledged. Patent was upheld. Decision here.