Tymlos® (abaloparatide)
Case Name: Radius Health, Inc. v. Orbicular Pharm. Techs. Private Ltd., Civ No. 22-11546-RGS, 2025 WL 2147860 (D. Mass. July 30, 2025) (Stearns, J.)
Drug Product and Patent(s)-in-Suit: Tymlos® (abaloparatide); U.S. Patent Nos. 8,748,382 (“the ’382 patent”), 8,148,333 (“the ’333 patent”), RE49,444 (“the ’444 patent”), 10,996,208 (“the ’208 patent”), and 11,782,041 (“the ’041 patent”)
Nature of the Case and Issue(s) Presented: Tymlos is used to treat osteoporosis. The API in Tymlos, abaloparatide, is a synthetic analog of the first 34 amino acids of parathyroid hormone related protein (“PTHrP”). Early attempts to formulate abaloparatide were unsuccessful due to challenges with impurities and stability. The claims of the ’382, ’333, and ’444 patents are directed to storage stable formulations of abaloparatide (“Formulation Patents”). During product development, Radius learned of a previously unidentified degradation in its drug product, and the ’208 and ’041 patents are directed to formulations that overcome this impurity (“Impurity Patents”). In September 2022, Radius sued Orbicular for patent infringement after Orbicular filed an ANDA with FDA seeking to market generic Tymlos. After a ten-day bench trial, the court entered judgment in favor Radius on all asserted claims, except for claim 2 and 11 of the ’333 patent.
Why Radius Prevailed: The court found the asserted claims of the of the ’382 and ’444 patents not obvious. Orbicular argued that Dong 2001 and the label to Forteo® rendered these claims invalid as obvious. Dong 2001 is a two-page abstract reporting that abaloparatide is twice as effective as teriparatide. Forteo® is an osteoporosis drug with teriparatide as the API—a different peptide that is an analog of parathyroid hormone but shares only 40% similarity with abaloparatide. The court found that Orbicular had not shown that a POSA had a reasonable expectation of success in combining the references to meet the limitations cited in the ’382 and ’444 patents: an optimal abaloparatide dosage that was twice as high as the maximum dosage reported in the Forteo® label. In particular, the court reached its no-expectation-of-success finding based on the fact that: (i) even a single amino acid (let alone more than half of the amino acids) in a sequence can significantly alter the properties of the peptide; (ii) Dong 2001 did not provide any data from the underlying animal studies and was not subjected to the peer review process; and (iii) the studies cited in Dong 2001 viewed the higher potency level of abaloparatide as paving the way for the administration of lower dosages of abaloparatide than teriparatide.
Next, the court found that claims 2 and 11 of the ’333 patent were obvious. Claim 2 recited a storage stable abaloparatide formulation with a pH of 5.1. Orbicular argued that the claim was obvious in light of the ’949 patent and the ’200 publication. The ’949 patent disclosed the chemical sequence for abaloparatide, while the ’200 publication disclosed the use of a buffer to maintain a preferred pH range of 3 to 6 in a peptide sharing 33 amino acids with abaloparatide. The court credited the testimony of Orbicular’s expert who testified that it was common knowledge that isomerization begins to fall at a pH of 5 and is minimized at a pH of 6. For this reason, the court found that it would be common optimization to reach a pH of 5.1. As to secondary indicia, the court found that industry praise, if any, was not tied to the claimed invention and that Radius had not met its burden to show unexpected properties. Claim 11 of the ’333 patent, which recited 5 mg/mL of phenol in the storage stable abaloparatide formulation, was also found to be obvious. The primary prior art disclosed the use of a preservative in peptide formulations and the other provided a high-level overview of phenol, which suggested a concentration of 0.5%. For this reason, the court found an expectation of success. For the same reason as explained above, the court found no secondary indicia of non-obviousness.
But the court found that claim 13 of the ’333 patent was not obvious. This claim recited a storage stable abaloparatide formulation without a chemical stabilizer. Orbicular relied on the ’114 prior-art patent, which disclosed hundreds of PTHrP analogs. But the court found that there was no evidence that a POSA would have reasonably expected from the ’114 patent that an abaloparatide formulation without a chemical stabilizer would be stable.
Finally, the court did not credit any of Orbicular’s Section 112 defenses. The court credited Radius’s expert who testified that a POSA would know as a matter of standard practice how to synthesize and/or purify the starting abaloparatide API from existing prior art and would not have to practice the “test and toss” method. Thus, the Impurity Patents were enabled. As to written description, Orbicular made essentially the same argument as it did with respect to enablement. For that same reason, the Impurity Patents were not invalid for lack of written description.
