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GEN News Highlights : Jan 7, 2014
CAR Wars: Startup Joins St. Jude in Gene Therapy Legal Wrangle vs. UPenn
Less than a month after launching with $120 million in funding, a cell therapy startup involving three prominent research institutions has joined a year-and-a-half old legal wrangle between the University of Pennsylvania and St. Jude Children’s Research Hospital over the technology for chimeric antigen receptors (CARs).
Juno Therapeutics has sided with St. Jude, from which it agreed last month to license exclusively St. Jude’s U.S. Patent No. 8,399,645, covering a chimeric antigen receptor technology for cancer immunotherapies. St. Jude contends that Penn wrongly used material covered by the ‘645 patent and two earlier materials transfer agreements (MTAs) in the development of its own chimeric T-cell receptor. Penn has asked the court to declare it had not infringed the patent or the two MTAs, and that the patent was invalid.
Juno was launched in December by Memorial Sloan-Kettering Cancer Center, the Fred Hutchinson Cancer Research Center, and Seattle Children’s Research Institute. Through its license agreement, Juno is obligated to “join as a party, and control, pursue, and defend” claims related to the two MTAs.
Under the first MTA in 2003, St. Jude provided an anti-CD19-BB-zeta chimeric T-cell receptor construct and a related gene sequence to Penn and Carl June, M.D., director of Translational Research in Penn’s Abramson Cancer Center. A second MTA in 2007 allowed Dr. June to use the construct in clinical trials.
St. Jude alleges Penn breached the MTAs by discussing commercializing the chimeric T-cell receptor material, and by incorporating much of the St. Jude-developed technology without acknowledging St. Jude as the source of material in the anti-CD19 CAR cDNA detailed by Penn in two journal articles.
Penn adds that Dr. June and colleague Michael Milone, M.D., Ph.D., developed a largely different CAR than that of a former St. Jude investigator, Dario Campana, M.D., Ph.D., though Penn’s director of legal affairs, Kathryn A. Donohue, acknowledged in a letter: “We incorporated the cDNA from Dr. Campana/St. Jude into the vector.”
Penn told St. Jude it was ending the MTAs in 2011. A year later, Penn joined Novartis in launching an alliance to expand use of personalized T-cell therapy. Novartis contributed $20 million toward a Center for Advanced Cellular Therapies with joint R&D focused on discovery, development, and manufacturing of adoptive T-cell immunotherapies.
St. Jude filed a complaint in July 2012 with the U.S. District Court Western District of Tennessee. Eight days later, Penn filed its own complaint against St. Jude in the district court’s Eastern District of Pennsylvania. Penn contended St. Jude tortuously interfered with the university’s prospective contractual relations, and denied having breached the MTAs. The cases were consolidated in October 2012, and the tort claim dismissed in April.
“If Dr. June and Penn commercially develop or exploit the Materials, their actions and omissions will deprive St. Jude and Juno of substantial income to which they are legally and equitably entitled,” Juno argued in a December 20 filing, without specifying how much income was at issue.
The ‘645 patent, issued March 19, 2013, lists two co-inventors, Chihaya Imai, M.D., Ph.D., and Dr. Campana. More than a decade ago they studied inserting CARs into T cells: One end of the CAR protrudes from the T cell, enabling it to latch onto a tumor cell antigen, while the CAR’s other end directs the T cell to destroy the target cell. The researchers replicated that result using a retroviral vector to insert cDNA—a DNA molecule containing a nucleotide sequence encoding the structure of the CAR—into the DNA of a T cell. When the T cell replicated, the new T cells also included the CAR.
In 2003, Dr. Campana presented a paper on the anti-CD19 chimeric receptor at an American Society of Hematology conference attended by Dr. June. He and Dr. Campana followed up with each other, with Dr. Campana agreeing to share with Dr. June “material” consisting of the anti-CD19 BB-zeta chimeric receptor construct, “including any progeny, portions, unmodified derivatives, and any accompanying know-how or data.”
Penn argues “material” did not broadly encompass any and all derivatives of the biological materials provided, while the sequence and the other information did not constitute “know-how” since sequences are readily obtainable by people skilled in molecular biology using common techniques.
According to the 2003 MTA—labeled “facially ambiguous” by District Court Judge Stewart Dalzell—“the material will only be used to create a lentiviral chimeric T-cell receptor construct to be used in preclinical studies”; may not be used in humans or “for any commercial purpose;” and that Penn “not commercialize any product that contains Material without the prior written approval of St. Jude.” St. Jude and Penn also agreed to jointly publish research results based on the material.
Penn concluded a lentiviral vector—a modified form of HIV-1—was a more effective way to genetically modify human T cells. The university created what it called a “modified derivative” of Dr. Campana’s CAR incorporating the modified anti-CD19-BB-ζ sequence into a lentiviral plasmid created earlier in Dr. June’s lab. The university CAR used a primer-based polymerase chain reaction to generate a DNA sequence similar to what Dr. Campana constructed, except to allow recombination into Penn’s lentiviral vector by including five nucleotide differences at the ends of the sequence.
St. Jude contends the identical approximately 1,500-base-pair sequence it provided was used by Penn, except for a single-base-pair difference. “Even with the base pair difference, the June Construct contains the largest possible nucleotide ‘portion’—all but one base pair out of approximately 1,500—of the anti-CD19 cDNA ‘Material’ St. Jude provided,” St. Jude argued in a legal filing.
Dr. Campana left St. Jude in 2011, to take his current position as professor in the Department of Pediatrics and principal investigator at Singapore’s National University Cancer Institute.
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