API and IP Newsletter
Contents
Recent FDA approvals
We follow FDA approvals especially approvals of small molecules. We analyse very brief IP situation, comment about synthesis, polymorphs salts etc.
In March 2023 FDA approved leniolisib. It is approved as a phosphate salt. Brand name JOENJA. The marketing authorisation is to treat adults and children 12 years of age and older who have activated phosphoinositide 3-kinase delta syndrome (APDS); APDS is a genetic condition that decreases the activity of the immune system and can result in recurrent infections.
Leniolisib phosphate is a white to yellowish to yellowish-greenish powder. The aqueous solubility of leniolisib phosphate is pH dependent with decreasing solubility observed with increasing pH. JOENJA film-coated tablets are for oral administration.
Each tablet contains 70 mg of leniolisib (equivalent to 85 mg leniolisib phosphate) with inactive ingredients such as colloidal silicon dioxide, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.
The tablet film-coating contains hydroxypropyl methylcellulose, iron oxide red, iron oxide yellow, polyethylene glycol, talc, and titanium dioxide.
Patent family WO2012004299A1, relates to compound and claims Markush claim.
An example 67 in WO2013001445A1 describes leniolisib. It is produced as per scheme 4 shown above.
(S)-3-Amino-1-tert-butyloxycarbonylpyrrolidione is RM used for synthesis of leniolisib. Many companies are importing this RM in India. GVK, Jubilant, Aurigene. These companies might be working on API development for their different clients for different purposes.
The anhydrous crystalline form and trihydrate crystalline form are claimed in WO 2013001445. Different salts are also claimed in the same patent family.
General information
More firms join litigation against Central govt on FDC ban
At least seven more pharma companies and a federation of pharma manufacturers have approached the Delhi High Court against the Central Government’s order in the beginning of June prohibiting manufacturing, distribution and sale of 14 fixed dose combinations (FDCs) licensed prior to the year 1988.
News here.
Roche sues Biogen over biosimilar of blockbuster arthritis drug
Roche and two of its subsidiaries sued biotech company Biogen in Massachusetts federal court on Thursday, accusing its proposed similar version of Roche's blockbuster rheumatoid arthritis drug Actemra of infringing several of their patents.
News here
Intellectual Property
Novartis lost Entresto case in Delaware District Court
U.S. District Court for the District of Delaware issued an unfavourable decision for Novartis regarding this US 8,101,659 patent (`659 patent). This patent relates to heart failure treatment using Entresto. The patent is due to expire on 15 July 2025. This patent was invalidated for the lack of written description.
What is the lack of written description?
In very simplistic explanation, the patents are nothing but contracts. The contracts are with Governments. Inventors add value to the existing science and hence Patent office (Government) grants patents to the inventors. In other words the Governments offer the right to the inventor/(s) to exclude others for practicing the invention for this value addition to the science. Hence, one of the requirement of granting the patent is, the inventors must be in the possession of the invention at the time of filing the patent application.
In this case, the defendants MSN and Hetero argued that the '659 patent is invalid for lack of written description. The Hon. Judge agreed to MSN and Hetero.
The touchstone of written description is possession of the invention as of the priority date. The function of the description requirement is to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.
MSN and Hetero contend that, because complexes were unknown as of the 2002 priority date, Novartis did not possess such complexes and therefore could not have described them.
Novartis’ position that, in 2002, complexes of valsartan and sacubitril, pharmaceutical complexes, and complexes, generally, were unknown to a Person of Ordinary Skills in the Art (POSA).
The Judge had found the same.
Thus, the Judge concluded that Novartis scientists, by definition, could not have possession of, and disclose, the subject matter of such complexes in 2002, and therefore, axiomatically, Novartis cannot satisfy the written description requirement for such complexes. The asserted claims are therefore invalid for lack of written description.
Novartis argued, the '659 patent satisfies the written description requirement by disclosing valsartan and sacubitril-the structural features (i.e., chemical names and/or chemical formulas) common to the members of the claimed genus of the pharmaceutical composition containing the valsartan and sacubitril combination.
Novartis pointed out that physical mixtures of valsartan and sacubitril, and complexes of valsartan and sacubitril, are mere subsets of the claimed genus. According to Novartis, written description does not require disclosure of structural features common to only a subset of the claimed genus, and therefore Novartis need not have disclosed complexes.
Novartis’ trouble is that written description also requires that common structural features be described with enough precision that a relevant artisan can visualize or recognize the members of the genus.
A broad outline of a genus's perimeter is insufficient.
As the Federal Circuit has explained:
Analogizing the genus to a plot of land, if the disclosed species only abide in a comer of the genus, one has not described the genus sufficiently to show that the inventor invented, or had possession of, the genus. One describes a plot of land by its furthest coordinates, in effect drawing a perimeter fence around it. That may be akin to the function of patent claims to particularly point out and distinctly circumscribe the outer boundaries of a claimed invention. With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.
The common features that Novartis identifies sacubitril and valsartan, draw a fence around a genus that includes both complexes and physical mixtures of valsartan and sacubitril. But the '659 Patent specification describes physical mixtures only. The specification did not, and could not, have allowed a POSA to visualize the members of the entire genus sufficient to show possession of complexes, which, to a POSA' s knowledge, had not yet been discovered.
Accordingly, the Judge found that MSN and Hetero have shown by clear and convincing evidence that the asserted claims of the '659 Patent are invalid for lack of written description.
Novartis will appeal this decision as per the latest news. In our view, this decision might not impact on generic launch date.
Decision here
