Intellectual Property Programs

Cayman is the industry leader in prostaglandin synthesis, with unmatched knowledge of eicosanoid chemistry and more than 40 years of experience. Our scientists use this knowledge with current opportunistic targets to invent novel therapeutics for bone growth and repair. Numerous patents have been filed for the complex synthesis of several small molecules, assay technologies, and the commercial manufacture of eicosanoids as Active Pharmaceutical Ingredients (APIs).

Learn more about these projects

• Small Molecule Therapeutics
• APIs

Small Molecule Therapeutics

Bone Growth and Repair Promoters (EP₄ Receptor Agonists)

Activation of the prostaglandin E receptor 4 (EP₄) via prostaglandin E₁ (PGE₁) and prostaglandin E₂ (PGE₂) causes an increase in intracellular cyclic AMP, which plays important roles in bone formation and resorption as well as in certain diseases. Because many development programs for systemic delivery of EP₄ agonists have failed for safety liabilities such as decreased blood pressure, attention shifted to localized delivery of anabolic agents to bone.

Cayman was approached by Myometrics, LLC for custom synthesis of a published, selective EP₄ receptor agonist to stimulate local bone formation. CAY10580 was synthesized, formulated in a bone matrix, and administered locally in an in vivo rat calvaria model of craniofacial defect as a proof-of-concept to study bone repair using a small molecule bone anabolic agent. Then, using Cayman’s synthetic and medicinal chemistry and structural biology expertise, SAR study identified and developed a new subclass of γ-lactam (pyrrolidinone) PGE₁ derivatives as highly selective EP₄ receptor agonists. From this project, multiple patents have been granted with others pending, culminating in the protection of Cayman catalog EP₄ agonist KMN-80 and lead compound KMN-159 in the invention of novel therapeutic agents for bone repair. These patented compounds can be formulated with a bone growth matrix and may be applicable to orthopedic, periodontic, or craniofacial disorders as well as general fracture repair.

Patents:

Scientific Posters:

• Novel Potent Lactam Acetylene EP₄ Agonists (PDF)
• Osteoblast Differentiation and Increased Rate of Bone Defect Repair (PDF)
• Development of a Novel Prostaglandin EP₄ Agonist Which Stimulates Local Bone Formation (PDF)
• A Novel Series of Selective Agonists Evaluated Against Rattus Norvegicus EP₄ Receptor (PDF)
• Evaluating contribution of bis-fluorination of selective γ-lactam agonists towards rat EP₄ prostanoid receptor (PDF)
• Novel, Potent, Selective, Small Molecule EP₄ Receptor Agonists Stimulate Rat Bone Marrow Stem Cell Differentiation (PDF)
• Biochemical and Molecular Characterization of the Osteoblastic Differentiation of Rat Bone Marrow Stem Cells Treated with KMN-159, a Novel Selective EP₄ Prostaglandin Receptor Agonist (PDF)
• Effects of a Novel EP₄ Agonist on Bone Metabolism in vitro (PDF)
• A Novel Selective EP₄ Prostaglandin Receptor Agonist, KMN-159, Induces Osteogenesis in Bone Marrow Stem Cells (PDF)
• KMN-159, a Novel EP₄ Receptor Agonist, Stimulates Osteoblastic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells (PDF)
• Release of the EP₄ Receptor Agonist KMN-159 from Scaffolds in vitro (PDF)

Publications:

APIs

Latanoprost and Bimatoprost

Latanoprost is the most widely used prostaglandin for the treatment of elevated intraocular pressure in glaucoma. It is the isopropyl ester of 17-phenyl-13,14-dihydro prostaglandin F_2α and a prodrug form of the free acid, which is a potent agonist of the FP receptor in the eye. Bimatoprost is also a potent FP receptor agonist that finds clinical use as an ocular hypotensive agent for the treatment of glaucoma. Cayman scientists hold compound-process patents for the methods to generate each compound.

Patents: