API and IP Newsletter
Contents
"Genetic priority score" promises to revolutionize drug development
Scientists hail new antibiotic that can kill drug-resistant bacteria
ANDA approvals in December 2023
We follow ANDA approvals mainly Indian companies. In December 2023, there were about total 72 ANDA approvals and out of which 9 were tentative approvals. Lupin and Zydus sought approvals for 4 ANDAs each. Total 37 approvals for Indian ANDA fliers. Some of our observations are as below.
General information
"Genetic priority score" promises to revolutionize drug development
Driven by the need for a better way to prioritize targets for drug development, the Icahn School of Medicine at Mount Sinai has led the development of a novel "genetic priority score" (GPS) that will integrate various types of human genetic data into a single easy-to-interpret score.
Studies have shown that drugs have an increased likelihood of success in clinical trials when the genes they target have been demonstrated to have genetic support. The new tool integrates multiple lines of genetic evidence to prioritize these drug targets.
News here.
Scientists hail new antibiotic that can kill drug-resistant bacteria
Scientists have discovered an entirely new class of antibiotic that appears to kill one of three bacteria considered to pose the greatest threat to human health because of their extensive drug-resistance.
Zosurabalpin defeated highly drug-resistant strains of Carbapenem-resistant Acinetobacter baumannii (Crab) in mouse models of pneumonia and sepsis, and was being tested in human trials.
News here
Intellectual Property
CAFC Affirmed PTAB Decision to Invalidate All Claims of United Therapeutics Patent US 10,716,793 (`793)
The '793 patent discloses a method of administering treprostinil by inhalation and was issued to United Therapeutics Corporation (UTC).
Liquidia submitted NDA No. 213005 under§ 505(b)(2) seeking FDA approval for the manufacture, use, and sale of its proposed product LIQ861 (Yutrepia™).
LIQ861 is a dry powder formulation of treprostinil sodium.
The FDA tentatively approved LIQ861 for the treatment of pulmonary arterial hypertension.
Liquidia's NDA contains Paragraph IV certifications alleging that '793 patent is invalid and/or will not be infringed by the manufacture, use, or sale of its proposed product.
U.S. Patent and Trademark Office Patent Trial and Appeal Board (“the Board”) in an inter partes review (“IPR”) concluded that claims 1–8 of U.S. Patent 10,716,793 (“the ’793 patent”) are unpatentable.
United Therapeutics Corporation (UTC) appealed the final written decision and the matter was before CAFC.
Claim 1 is the only independent claim in the `793 patent. It reads as follows:
1. A method of treating pulmonary hypertension comprising administering by inhalation to a human suffering from pulmonary hypertension a therapeutically effective single event dose of a formulation comprising treprostinil or a pharmaceutically acceptable salt thereof with an inhalation device, wherein the therapeutically effective single event dose comprises from 15 micrograms to 90 micrograms of treprostinil or a pharmaceutically acceptable salt thereof delivered in 1 to 3 breaths.
UTC raised three challenges on appeal. First, it argued that the Board erred in determining that the Voswinckel abstracts are prior art. Second, it argued that, even if those abstracts are prior art, the Board erred in finding that the claimed dose would have been obvious over US 6,521,212 (the ’212) patent in combination with the Voswinckel abstracts. And finally, it argues that the Board legally erred in its treatment of dependent claims 4, 6, and 7, and that its obviousness determination as to those claims was not supported by substantial evidence.
Voswinckel abstracts
JESC is an abstract that describes a study in which patients inhaled solutions of treprostinil in concentrations of 16, 32, 48, and 64 μg/mL via a nebulizer.
JAHA is an abstract that describes a study in which patients inhaled solutions of treprostinil sodium via a nebulizer in 3 single breaths.
CAFC found that the Board’s conclusion that the Voswinckel abstracts were sufficiently disseminated such that each constituted a printed publication was supported by substantial evidence. Specifically, the Board determined that the two 2004 conferences at which the abstracts were presented were attended by over 20,000 attendees. And both Liquidia’s and UTC’s experts testified that every attendee of either conference would have received a copy of the abstract book in which each of the Voswinckel abstracts appeared. Further still, the Board found that neither abstract book would have been disseminated with any expectation of privacy, given that the conference attendees included scientists, physicians, and nurses, as well as journalists.
CAFC opined and supported the Board’s conclusion that the Voswinckel abstracts qualify as prior art.
Claim 1 requires the inhalation of a therapeutically effective single event dose of 15 micrograms to 90 micrograms of treprostinil or a therapeutically acceptable salt thereof. The Board concluded that, although no reference explicitly taught this dose, the person of ordinary skill in the art would have understood the solutions in JESC to have delivered an amount of treprostinil within the claimed range. That finding was supported by substantial evidence
JESC discloses the administration of treprostinil solution via a nebulizer to patients in concentrations of 16, 32, 48, and 64 μg/mL.
As the Board recognized, JESC does not disclose the volume of solution administered, which is necessary to calculate the amount (in μg) of treprostinil administered.
Accordingly, the Board looked to the declarations of Liquidia’s two experts, each of which testified that, at the time of the invention, nebulizers delivered at least 1 mL and up to 5 mL of solution.
Based on those delivery volumes, the Board concluded that the amounts of treprostinil delivered in JESC would have been from 16–80, 32– 160, 48–240, or 64–320 μg, each of which has at least one endpoint that falls within the claimed range of 15–90 μg.
UTC argued that the Board’s conclusion was error because the experts’ testimony related only to fill volume, not volume actually delivered.
Because no nebulizer can be 100% efficient, UTC argued it was error to rely on the experts’ testimony without accounting for other factors, such as patients’ breathing volume and patterns, and individual nebulizer characteristics (e.g., residual volume, nebulization rate, etc.).
But the Board considered, and rejected, those same arguments. Specifically, it concluded that, “to the extent that something less than the entire fill volume was delivered to the patient, the preponderance of the evidence still supports actual delivered solution volume being at least one milliliter.”
And, to be sure, UTC’s own expert testified that, in 2006, he had not administered treprostinil via a nebulizer that utilized less than one milliliter of drug solution.
Accordingly, the Board’s finding that the combination of the ’212 patent, JESC, and JAHA would have rendered obvious claim 1 was supported by substantial evidence.
Thus, CAFC affirmed the earlier decision by the Board which found all claims of U.S. Patent No. 10,716,793 (‘793 Patent) to be unpatentable due to the existence of prior art cited by Liquidia in inter partes review (IPR) proceedings.
As a result of the decision, Liquidia announced, it will immediately seek to set aside the injunction issued by the U.S. District Court for the District of Delaware (District Court) in the lawsuit filed by UTC under Hatch-Waxman Act and pursue final regulatory approval of YUTREPIA by the FDA.
Prior Art Documents
R. Voswinckel et al., Inhaled treprostinil is a potent pulmonary vasodilator in severe pulmonary hypertension, 25 EUROPEAN HEART J. 22 (2004), J.A. 1234–1240.
Robert Voswinckel et al., Inhaled Treprostinil Sodium (TRE) For the Treatment of Pulmonary Hypertension, in Abstracts from the 2004 Scientific Sessions of the American Heart Association, 110 CIRCULATION III-295 (Oct. 26, 2004), J.A. 1241–43.
Decision here
