AstraZeneca has signed two deals worth $1.35 billion with Alteogen to develop subcutaneous versions of the British pharma’s cancer drugs despite a potential patent infringement risk.
Monday, AZ said it has acquired exclusive rights to use Alteogen’s hyaluronidase protein, ALT-B4, to develop and commercialize subcutaneous formulations of “several oncology assets.”
In its filings to the Korea Exchange, Alteogen disclosed two separate agreements that total $1.35 billion. One includes $25 million in upfront payment and up to $725 million worth of milestones; and the other $20 million upfront and $580 million in milestones, according to a Google translation of the documents.
AZ declined to disclose the specific assets involved or financials.
AZ signed the Alteogen collaboration despite an escalating patent dispute around ALT-B4, a human recombinant hyaluronidase enzyme that can enable a large volume of under-the-skin administration of drugs that are otherwise typically administered as intravenous infusions.
Halozyme, developer of rival hyaluronidase enzymes, has threatened to sue Merck & Co. over its subcutaneous Keytruda, which utilizes the Alteogen technology. The U.S. drug delivery specialist argues that ALT-B4—if used in a commercial product—would infringe on its Mdase portfolio of modified hyaluronidases. Merck plans to launch the new Keytruda formulation in the U.S. this year pending FDA approval.
Halozyme said it has reached out to Merck for a potential license agreement but is prepared to pursue an injunction against the sale of subcutaneous Keytruda through a lawsuit.
For its part, Merck has requested the U.S. Patent and Trademark Office to reconsider seven Mdase patents out of a total of about 100.
When asked whether AZ expects a similar patent dispute or a separate deal with Halozyme, an AZ spokesperson said the company cannot comment on third-party patents, and that it looks forward to working with Alteogen.
Besides Merck and AZ, Alteogen has recently teamed with Daiichi Sankyo to develop a subcutaneous version of the Japanese pharma’s antibody-drug conjugate Enhertu, which is partnered with AstraZeneca.
Daiichi declined to comment on the Merck case’s potential impact on its own Alteogen partnership.
“It is our goal to sign a license agreement with any company using our intellectual property to deliver drugs subcutaneously with a modified human hyaluronidase,” Halozyme CEO Helen Torley said in response to a Fierce Pharma inquiry last week about the Daiichi-Alteogen pact.
Apparently facing questions following Merck’s patent move, Alteogen in a November investor communication (Korean) stressed that the ALT-B4 patents are confirmed through in-depth analysis by both the company and each licensing partner via multiple patent law firms, according to a Google translation of the statement.
While patent protection for ALT-B4 is expected to expire in 2040, the Mdase portfolio of patents last until 2034 in the U.S. Different from Halozyme’s widely used Enhanze technology, which provides partners a specific hyaluronidase protein, Mdase represents a group of patents.
Halozyme’s IP is very broad, covering “every peptide which has 95% sequence identity to a modified hyaluronidase PH20 peptide,” Evercore ISI analyst Umer Raffat said in a recent note to clients.
Raffat expects that Merck and Halozyme will settle. The USPTO likely won’t give what Merck wants given the language used in Halozyme’s patents is not new, while Halozyme’s broad patent claims may be vulnerable in a lawsuit, he argued.
Back in 2023, the U.S. Supreme Court nixed Amgen’s PCSK9 patent bid against Sanofi because the subject patent was too broad. In a unanimous vote at the time, SCOTUS ruled that Amgen’s Repatha patents—which covered all antibodies that bind to particular amino acids on PCSK9—were invalid because they didn’t include a sufficient description to enable a skilled person to create the full scope of Amgen’s claims through a reasonable degree of experimentation.
“[S]uch written description/enablement for [Halozyme]’s broad patent would have to be established in conjunction with functional limitations limits (e.g., “increased hyaluronidase activity”)—and there’s already evidence that perhaps up to 87% of PH20 sequences potentially covered by [Halozyme]’s new IP have Less activity than unedited PH20,” Raffat noted as a potential problem for Halozyme.
Editor's Note: The story has been modified at two spots to correctly reference Halozyme and to update the nature of Mdase as a portfolio of patents.