API and IP Newsletter

 

Contents

• Patent portfolio of Sun Pharma. 

• General information. 

• Biogen’s New Alzheimer’s Drug Beyond Reach for Many Patients. 

• Indian pharmaceutical industry to reach $60bn in two years. 

• Intellectual Property. 

• Ibrutinib decision by Delaware Court 

Patent portfolio of Sun Pharma

We study patent portfolios of various companies. We assess the strength of the patent portfolio and try to understand the direction of the company.  

Recently we looked at the patent portfolio of Sun Pharma for a period of about one and half years. We mainly considered PCT applications published during this period, which would reflect the active development period on 2018-2019-2020. This lag time is primarily due to time taken for patent publication which is about 18 months from the priority date.  

Below are the most interesting applications during this period. 

Publication Number	SIDVIM comments
WO2020183322A1	Injectable formulations of fenoldopam  are listed in OB as antihypertensive drug. The company is developing topical compositions for the treatments for psoriasis.
WO2020170198A1	This invention relates to infusion containers for Midazolam. The inventors have stabilized the formulation by designing an innovative infusion container which not only solves the problems associated with physicochemical stability of Midazolam or a salt, but also allows ease of administration of a second sterile fluid, if needed.
WO2021053651A1	Plant extract to treat Covid. One of the many attempts by companies. This was filed 27 April 2020! Seems one of the first few attempts to treat covid. In December DCGI rejected Sun's application for emergency use to treat Covid.
WO2020148609A1	The undesirable impurities generated are epinephrine sulphate and D-epinephrine in epinephrine compositions. The present invention provides a stable, aqueous injectable solution comprising epinephrine, the solution is free of an inorganic acid and inorganic base.
WO2021024237A1	Invention relates to aqueous solution of norepinephrine.  The present inventors discovered that generation of these impurities are controlled using combination of stabilizers selected from antioxidants and an ion chelator.
WO2021019523A1	The drug  cariprazine hydrochloride received FDA approval on 17 September 2015. Sun had filed DMF in July 2019
WO2021090177A1	The use of sinococuline, magnoflorine, makisterone A and hydroxy ecdysone compounds. The present disclosure provides certain compounds synthesized or isolated from the plant, and various extracts from the plants to effectively prevent and treat the Dengue viral disease.
WO2021079339A1	The drug cetrorelix  approved in 2000 for GnRH. No Gx yet. The parenteral dosage form comprising the ready-to-inject aqueous solution of cetrorelix acetate of the present invention remains stable at room temperature for a prolonged period of time whereby there occurs substantially no degradation or increase in level of Impurity A. Maybe Sun would file first ANDA? Sun filed DMF in March 2020.
WO2020212874A1	Research on monoclonal antibodies. A method of treating psoriatic arthritis comprising administering an anti-IL-23p 19 antibody huml3B8-b to a patient
WO2021074898A1	New compounds to treat Pancreatic cancer
WO2021038540A1	New compounds as BTK inhibitor and allegedly superior to Ibrutinib. C481S BTK mutation has been reported to diminish ibrutinib’s potency up to 500- fold and prevents its covalent binding, rendering it unable to effect irreversible inhibition of BTK. New compounds of Sun allegedly solve this problem!
WO2021014386A1	The present invention relates to a selective estrogen receptor degrader (SERD) and new compounds.
WO2021005583A1	Camptothecin, a plant alkaloid isolated from Camptotheca acuminata (family Nyssaceae), was first discovered in the early 1960s. This invention relates to novel derivatives of camptothecin that exhibit improved solubility and stability and reduced toxicity while retain the desired pharmacological activity.
WO2020250133A1	This seems to be an old compound in Sun Pharma's library. It was earlier tested for Parkinson's disease, neurodegenerative disorders. Now it is being tested for synucleinopathies

Conclusions:

1.      Good mix of NCEs, mAbs and new formulations of molecules in IP portfolio.

2.      Now many applications on mere chemical processes.

3.      Patent applications are backed by DMF filings and are with clear view of commercialization

4.      Plant extracts and new indications of old molecules in own library are also being explored.

5.      The company is moving in the direction of NCE and to some extent in biologics. The focus on vanilla generics could be reduced and more emphasis will be given on niche molecules, specialty molecules (such as cetrorelix) and value added generics.

6.      Overall, very strong IP portfolio.

 

General information

Biogen’s New Alzheimer’s Drug Beyond Reach for Many Patients

Many Alzheimer’s clinics are holding off on prescribing Aduhelm until federal officials decide next year if Medicare will pay for it. 

News here. 

Indian pharmaceutical industry to reach $60bn in two years

In its report on the Indian pharma sector on Thursday, it said that it expected the industry to reach USD60bn (INR4.4trn) size during this period due to the predominance of Indian pharmaceutical market in the generic segment.

"The main factors that are expected to drive the growth of the industry are (a) ability to leverage the opportunity available for Indian pharma companies due to expiry of the patent drugs across the globe, (b) ebbing of regulatory risks, (c) adoption of various strategies to de-risk from dependency on China for key raw materials, (d) increasing trend in private equity investments, and (e) solid fundamentals of the industry," according to the report. 

News here.

 

Intellectual Property

Ibrutinib decision by Delaware Court

Court upheld below listed OB patents of AbbVie's Ibrutinib (Imbruvica).

There are several patents listed in OB, following patents are of particular interest of this litigation. 

Patent No	Patent Expiration	Claims
US 8008309	13 November 2027	Compound patent
US 8754090	06 March 2031	Method of use patent
US 9655857	03 March 2036	Composition patent
US 9725455	06 March 2033	Polymorph patent

 

US 8,008,309: THE #309 PATENT (THE COMPOUND PATENT) 

Claim 10 of the #309 patent claims ibrutinib, the active ingredient of Imbruvica®. Alvogen argued that claim 10 is invalid because it was anticipated by Pan article, which was published on 12 December 2006.

The parties agreed that the Pan article and its supporting Information describe ibrutinib.

They disputed, however, whether Pan was published before the date of ibrutinib's invention. 

Pharmacyclics argued, two provisional patent applications (60/826,720  and 60/828,590 ) of # 309 were filed with the USPTO before Pan was published.

Provisional Application Nos. 60/826,720 (the #720 application) filed on 22 September 2006, and 60/828,590 (the #590 application) filed on 6 October 2006. 

The two provisional applications, both disclose the following reaction scheme for the synthesis of ibrutinib:

The parties argued whether the provisional applications enabled the starting material (intermediate 2) for synthesis of Compound 4. It was pointed out the chemical structure above the "2" in the diagram of the reaction pictured above is Intermediate 2. 

The #590 application also disclosed the following reaction scheme for the synthesis of Compound 6 (Ibrutinib)

Court concluded,

1.  Pharmacyclics has produced sufficient evidence and argument to show that the #720 application and #590 application contain written descriptions that support all the limitations of claim 10 of the #3 09 patent.

2.  Alvogen, on the other hand, has failed to prove by clear and convincing evidence that claim 10 of the #309 patent is not entitled to the filing date of either the #720 application or #590 application.

3.  The Court therefore found that claim 10 of the #309 patent has a filing date of 22 September 2006. Claim 10 is presumed to have been invented on that date and therefore cannot be anticipated by Pan, since Pan's publication date is 12 December 12 2006.

4.  Claim 10 of the #309 patent is thus not invalid. 

US 8754090: THE #090 PATENT (THE METHOD OF US -MANTLE CELL LYMPHOMA) 

Claims are as below

1.      A method for treating mantle cell lymphoma in an individual who has already received at least one prior therapy for mantle cell lymphoma comprising administering to the individual once per day between about 420 mg to about 840 mg of an oral dose of Ibrutinib

2.      The method of claim 1, wherein the once per day oral dose is about 560 mg. 

Here the main prior art was Phase I study document.

The court said, the mere fact that ibrutinib was being studied in a Phase I trial does not speak to ibrutinib’s efficacy. Less than 5% of oncology drugs that enter a Phase I trial ultimately receive FDA approval. Thus, a broad Phase I study protocol would not have motivated a skilled person to use ibrutinib to treat mantle cell lymphoma and derived dose of about 560 mg. 

So generics are unlikely until March 2031. The generic launch date could be further delayed based on Paediatric extension, polymorphs and compositions used by the generics. 

Decision here.

Disclaimer

Sidvim LifeSciences Private Ltd has taken due care and caution in developing this document. Since the data used for analysis in this document is based on the information available in the public domain, its adequacy or accuracy or completeness cannot be guaranteed. This document is for information only and Sidvim is not responsible for losses that may or may not arise due to any decisions made based on the same. No part of the document shall constitute or be represented as a legal opinion of any kind or nature. No warranties or guarantees, expressed or implied, are included in or intended by the document, except that it has been prepared in accordance with the current generally accepted practices and standards consistent with the level of care and skill exercised under similar circumstances by professional consultants or firms that perform the same or similar services.