As the patent war over global subcutaneous injection (SC) formulation technology intensifies, Halozyme Therapeutics in the United States has expanded the front by filing a petition to invalidate Alteogen's manufacturing process patent.
Alteogen said on the 12th that "Halozyme filed an inter partes review (IPR) with the Patent Trial and Appeal Board (PTAB) under the U.S. Patent and Trademark Office against the company's patent related to the manufacturing method for hyaluronidase." The patent at issue covers a process for culturing and producing the hyaluronidase enzyme and is separate from the composition-of-matter patent that protects Alteogen's core subcutaneous conversion technology "ALT-B4" itself.
Inter partes review (IPR) is a system in which a third party argues that "the patent can be sufficiently explained by prior art" and seeks to invalidate it. However, the invalidity must be proven "by documentary evidence alone," making the entry barrier and difficulty high.
◇ Halozyme says it is fully predictable from prior art… Alteogen says it is ready to respond
Halozyme argues that Alteogen's patent (U.S. Patent No. 12,221,638) is merely a simple combination of existing technology and is hard to regard as a new invention, seeking invalidation.
Citing its own prior patent (EP3037529) and a published technical document (WO2017/011598), the company's position is that "the process of lowering cell culture temperature to increase protein productivity is already a known concept, and the 'unpredictable effect' claimed by Alteogen is also described in the prior art."
Alteogen's patent contains a manufacturing method that suppresses sialylation, which reduces enzyme activity, by lowering the cell culture temperature from 37℃ to a range of 28–34℃, and raises activity to 10,000 units (Units/mL) or higher.
Halozyme says, "The examples in our patent already include high-activity data at around 17,000 units," and claims the patent was granted without properly reflecting this during examination.
Alteogen immediately pushed back. The company said, "We were already aware of the contents of the patent that Halozyme claims as prior art and have completed our analysis," adding, "We cannot disclose specific strategies, but we have prepared response measures and are strongly confident in the validity of the patent."
It added, "Since our partners signed license agreements after completing prior art reviews and due diligence, they have already confirmed that there are no issues in using the patent."
◇ Halozyme, MSD, and Alteogen widen global legal battle into a triangular front
The IPR petition came right after a German court sided with Halozyme and issued a preliminary injunction temporarily halting sales of Merck's (MSD) "Keytruda SC." Industry watchers view it as a strategic move by Halozyme to shake the technological underpinnings of Alteogen to gain negotiating leverage or to slow a rival's market entry.
Keytruda SC uses Alteogen's ALT-B4 technology. ALT-B4 is a technology that converts intravenous antibodies and biologics into subcutaneous injections to greatly reduce administration time, and Alteogen granted rights to use the technology by signing a license agreement with MSD in Jun. 2020.
However, MSD went on the offensive first this year by filing more than 10 post-grant reviews (PGRs), arguing that the patent for Halozyme's subcutaneous conversion technology "MDASE" is overly broad.
In response, Halozyme filed a patent infringement lawsuit against MSD in U.S. federal court and regained the upper hand in Germany by securing a preliminary injunction banning sales of Keytruda SC.
Amid this, Halozyme has taken direct aim at Alteogen's patent in the United States, and the legal clash over the SC formulation market is spreading into a more complicated "triangular full-scale war."
Alteogen said, "Our legal counsel in the United States will respond according to the strategy already in place," adding, "We will promptly share key developments."