API and IP Newsletter- Recent ANDA approvals and Roxadustat decision by EPO: T 0072/23
Contents
Recent ANDA approvals
General information
Jazz pays $145m to resolve Xyrem antitrust disputes
Bristol Myers Freed From Blood Cancer Drug Antitrust Litigation
Intellectual Property
Roxadustat decision: T 0072/23 (Photostable roxadustat formulation/FIBROGEN)
Recent ANDA approvals
We track ANDA approvals monthly. This report discusses the ANDA approvals obtained by generic companies in March 2025. There are approximately 86 ANDA approvals for March 2025, of which 23 are tentative approvals. Interestingly, out of the total 86 approvals, 47 were received by Indian companies.
Below is the list of top ANDA approvals.
Some of our observations for the approved products are as follows.
General information
Jazz pays $145m to resolve Xyrem antitrust disputes
Jazz Pharma has agreed to pay $145 million to settle lawsuits claiming it illegally acted to prevent generic versions of its narcolepsy therapy Xyrem from entering the US market.
The lawsuits – which date back to 2020 in some cases – have claimed that Jazz entered into a series of "reverse payment" agreements – sometimes referred to as "pay-for-delay" deals – which were designed to extend its monopoly by blocking access to more affordable generic drugs, forcing purchasers to buy expensive brands instead.
News here
Bristol Myers Freed From Blood Cancer Drug Antitrust Litigation
• Judge says plaintiffs failed to state monopolisation claims
• Bristol sued for restraining trade for Pomalyst drug
Bristol-Myers Squibb Co. got dismissal of a lawsuit alleging the company used reverse-payment agreements to delay the generic version of blood cancer drug Pomalyst, after a federal judge ruled the plaintiffs failed to state a claim.
“Plaintiffs have not plausibly alleged that the settlements were fraudulent, i.e., that they contained unlawful reverse payments,” Judge Edgardo Ramos of the US District Court for the Southern District of New York said in a Tuesday opinion and order that granted Bristol’s motion to dismiss.
News here
Intellectual Property
Roxadustat decision: T 0072/23 (Photostable roxadustat formulation/FIBROGEN)
Background
This is a decision by the European Patent Office's Boards of Appeal regarding a patent (EP 3003284) concerning pharmaceutical formulations of roxadustat. The patent was issued to Fibrogen, Inc.
The patent opponents are Teva Pharmaceutical Limited and Sandoz AG. They appealed against an earlier decision to maintain the patent in amended form.
The central issue concerns the inventive step of a tablet formulation that includes roxadustat, a photostabilising agent (titanium dioxide), and at least one additional dye (red, orange, or yellow) to safeguard the drug from photodegradation.
Claims:
Claim 1 of the main request held allowable by the opposition division read as follows:
"1. A tablet comprising roxadustat, a pharmaceutically acceptable excipient, and an effective amount of a photostabilising agent, wherein the photostabilising agent comprises titanium dioxide and at least one additional dye selected from the group consisting of, a red dye, an orange dye, a yellow dye, and combinations thereof, and wherein
(i) the photostabilising agent is blended into the tablet; or
(ii) the tablet comprises a tablet core and a coating and the photostabilising agent is blended into the tablet core; or
(iii) the tablet comprises a tablet core and a coating and the tablet core comprises roxadustat and the pharmaceutically acceptable excipient, and the coating comprises the photostabilising agent."
Key Arguments and Prior Art
The opponents, Teva and Sandoz, argued that adding a photostabilising agent to roxadustat was obvious due to the general knowledge about photostability testing and the use of UV-VIS absorbents and opacifiers in pharmaceutical formulations.
They cited prior art documents, which include:
The opponents contended that a skilled person, aware of roxadustat's light sensitivity, would routinely add a UV-VIS absorbent and an opacifier like titanium dioxide, along with a suitable dye based on the principle of spectral overlay.
The patent proprietor (Fibrogen) argued that the prior art did not suggest roxadustat was photosensitive and that combining titanium dioxide with a specific dye was not an obvious solution. They emphasise that photostability was just one of many properties to be studied and that the prior art suggested light-resistant packaging as an alternative.
Board's Reasoning
The Board of Appeal sided with the opponents (ie Teva and Sandoz), concluding that the claimed invention lacked an inventive step. Their reasoning included:
- Admittance of Argument: The Board admitted an argument from one of the appellants relating to the technical effect shown in Table 7 of the patent, finding it relevant to assessing the objective technical problem.
- Closest Prior Art: The Board agreed that D1 was the closest prior art.
- Difference and Technical Effect: The Board acknowledged that the claimed invention differed from D1 by formulating roxadustat with a photostabilising agent comprising titanium dioxide and a dye. The technical effect was improved photostability.
- Objective Technical Problem: The Board defined the objective technical problem as providing a composition comprising roxadustat having improved stability.
- Obviousness:
- The patentee argued that adding a photo-stabilising agent, as defined in claim 1 was not obvious for two reasons. First, using a photostabilising agent was not the preferred solution against photodegradation. D4 stated that the most common method to protect photosensitive drugs is to place the drug product in a protective market pack or in a coloured or amber immediate container. This teaching aligns with the flow chart in D5 and D16, which indicates that the immediate solution against photodegradation involves putting the drug product into light-resistant packaging. Reformulating the product to include a photo-stabilising agent was a last-resort measure that should be avoided because reformulation entails repeating many of the tests required by regulatory authorities for the reformulated product
- Second, the principle of spectral overlay was not reliable because a formulation could contain photosensitising excipients, meaning excipients that absorb energy at wavelengths outside the drug's absorption range but subsequently transfer the absorbed energy to the drug, causing its degradation. Therefore, the photostability of a drug in a formulation could not be predicted solely from the absorption spectrum or the stability studies of the drug in a pure solvent. Furthermore, titanium dioxide would not be chosen as the opacifier due to its absorption gap between 400 and 420 nm. Other opacifiers, such as iron, would be preferred oxides.
- The Board disagreed with the patentee.
- The Board found the solution proposed in claim 1 obvious. The Board reasoned that:
- Photostability testing is an essential part of drug development.
- A skilled person would necessarily test roxadustat's photostability and find it degrades upon exposure to light.
- Common general knowledge (D6, D9, D11) teaches the use of UV-VIS absorbents and opacifiers to reduce photodegradation.
- The principle of spectral overlay would guide the selection of suitable dyes.
- Titanium dioxide is a typical opacifier.
- Combining dyes with titanium dioxide is a known approach.
- Auxiliary Requests: The Board also found auxiliary requests 3-A (limiting the additional dye to a red dye) and 5-A (specifying Allura Red AC aluminium lake) to lack an inventive step. The Board reasoned that the selection of a red dye was obvious and that there was no evidence Allura Red AC provided a surprisingly better effect.
Decision
The Board of Appeal decided to:
1. Set aside the decision under appeal.
2. Revoke the patent.
In essence, the Board concluded that formulating roxadustat with a photostabilising agent that includes titanium dioxide and a dye was an obvious step for a skilled person in the field, considering the general knowledge and standard practices in pharmaceutical formulation.
Decision here
