Cayman’s Intellectual Property Programs | Cayman Chemical

Cayman’s Intellectual Property Programs

Cayman is the industry leader in prostaglandin synthesis, with unmatched knowledge of eicosanoid chemistry and more than 30 years of experience. Our scientists use this knowledge with current opportunistic targets to invent novel therapeutics for bone growth and repair and to address muscle necrosis associated with muscular dystrophy. 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

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:

North American Patents European Patents Australian & Asian Region Patents
  • AU 2013292357
  • AU 2014229065
  • JP 6141430
  • CN 104583201
  • IL 236637**
  • KR 2015036652**
  • IN 2015CN00937**

**application pending

Scientific Posters:

Publications:

Paper forthcoming…

Duchenne Muscular Dystrophy (H-PGDS Inhibitors)

Hematopoietic-type Prostaglandin D Synthase (H-PGDS) produces the pro-inflammatory mediator prostaglandin D2 (PGD2).  H-PGDS is expressed in muscle fibers from patients with Duchenne Muscular Dystrophy (DMD) and polymyositis. It is known to play a role in the etiology of the muscle necrosis associated with these conditions. Targeting H-PGDS with small molecule inhibitors is therefore a reasonable approach to the potential discovery and development of therapies for treatment of DMD and other inflammation-related disorders.

Through rational and structure-based drug design, Cayman scientists have discovered a new series of compounds that bind to the H-PGDS substrate binding site and inhibit PGD2 production. These potent H-PGDS inhibitors address potential amide metabolic (hydrolytic) liabilities of published compound series by Sanofi-Aventis and Pfizer by replacing the amide linker moiety between the pyrimidine core and the tail group with hydrolytically-stable, five-membered heterocycle ring isosteres such as imidazolyl and pyrazolyl moieties. This novel series also investigates SAR with regard to the insertion of an oxygen spacer between the head group and the core heterocycle. To evaluate the activity of these novel compounds, our scientists invented and validated a robust H-PGDS Fluorescence Polarization Binding Assay (Prostaglandin D Synthase (hematopoietic-type) FP-Based Inhibitor Screening Assay Kit - Green).

Work will continue in collaboration with Yoshihiro Urade from the University of Tsukuba International Institute for Integrative Sleep Medicine to improve the pharmacokinetics and metabolic stability of these compounds to move them forward into pre-clinical testing with an mdx mouse model of DMD.

Patents:

North American Patents European Patents Australian & Asian Region Patents
  • AU 2009292931
  • JP 5653356
  • PH 12011500593
  • KR 1406433

Scientific Posters:

APIs

Treprostinil

Treprostinil (sodium) is a prostacyclin (PGI2) analog and potent vasodilator used for the treatment of pulmonary arterial hypertension. Cayman scientists hold compound-process patents for its synthesis.

Patents:

North American Patents European Patents Australian & Asian Region Patents
  • AU 2013355130**
  • JP 2016504303**
  • KR 2015091170**
  • CN 104837806**
  • IL 239172**
  • IN 2015KN01824**
  • SG 10201600303

**application pending

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 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:

North American Patents European Patents Australian & Asian Region Patents
  • AU2009354014
  • JP 5318288
  • KR 1561171
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