Orally administered drug with extended release for obesity treatment

This technology is a nanoparticle-based drug that can be administered orally for effective systemic delivery and sustained release of the appetite-suppressing hormone lipocalin-2 (LCN2) to treat obesity and metabolic diseases.

Unmet Need: Effective but patient-friendly drug for treatment of obesity and metabolic diseases

Current methods of treating obesity with hormone agonists to suppress appetite have been effective in reducing weight, but their method of delivery — subcutaneous injection — poses an obstacle to patient adherence. While switching to oral formulations can improve medication adherence, safely delivering hormones at effective doses to the bloodstream is a challenge because of the stomach’s acidic environment and the intestinal epithelium’s limited permeability. Additionally, expanding the use of appetite-regulating hormones to metabolic diseases such as diabetes remains limited by delivery challenges.

The Technology: Efficacious, extended-release oral formulation of hunger-suppressing hormone

This technology is an orally administered obesity treatment, called LIGNOCAL, that is designed to enable high bioavailability of the appetite-suppressing hormone lipocalin-2 (LCN2) through nanoencapsulation. The polymers used to encapsulate LCN2 into nanoparticles protect the hormone across the wide pH range of the gastrointestinal tract and facilitate its transport into the bloodstream while showing low cytotoxicity. Sustained release of LCN2 by the nanoparticles maintains a bioactive systemic LCN2 concentration for at least two days and enables delivery of LCN2 to the hypothalamus, pancreas, and fatty tissues, where LCN2 decreases appetite, increases -islet cells and insulin secretion, increases energy expenditure, and maintains glucose metabolism to exert its weight-regulatory effects.

This technology and its short-term weight loss effect have been validated in LCN2 knockout mice. Cytotoxicity screening of this technology has been conducted in hematopoietic stem cells. The effects of LCN2 have been validated in lean or obese mice and non-human primates.

Applications:

• Treatment for obesity and diabetes
• Prevention of cardiovascular diseases and other diseases associated with obesity and metabolic dysfunction
• Therapy to enhance metabolic regulation
• Research tool for obesity, diabetes, metabolism, appetite, endocrine system, and endocrine function of bone
• Oral delivery of other macromolecules
• Weight loss drug

Advantages:

• Oral formulation for better patient compliance
• Effective systemic delivery
• Sustained release for maintaining bioactive systemic concentration
• Utilizes a short half-life, fast-acting hormone
• Low cytotoxicity

Lead Inventor:

Kam Leong, Ph.D.

Patent Information:

Patent Issued (WO/2025/081192)

Related Publications:

• Yoshinaga N, Zhou JK, Xu C, Quek CH, Zhu Y, Tang D, Hung LY, Najjar SA, Shiu CYA, Margolis KG, Lao YH, Leong KW. “Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery.” Nano Lett. 2023 Feb 8; 23(3): 757-764.

• Petropoulou PI, Mosialou I, Shikhel S, Hao L, Panitsas K, Bisikirska B, Luo N, Bahna F, Kim J, Carberry P, Zanderigo F, Simpson N, Bakalian M, Kassir S, Shapiro L, Underwood MD, May CM, Soligapuram Sai KK, Jorgensen MJ, Confavreux CB, Shapses S, Laferrère B, Mintz A, Mann JJ, Rubin M, Kousteni S. “Lipocalin-2 is an anorexigenic signal in primates.” Elife. 2020 Nov 24; 9: e58949.

• Mosialou I, Shikhel S, Luo N, Petropoulou PI, Panitsas K, Bisikirska B, Rothman NJ, Tenta R, Cariou B, Wargny M, Sornay-Rendu E, Nickolas T, Rubin M, Confavreux CB, Kousteni S. “Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes.” J Exp Med. 2020 Oct 5; 217(10): e20191261.

• Mosialou I, Shikhel S, Liu JM, Maurizi A, Luo N, He Z, Huang Y, Zong H, Friedman RA, Barasch J, Lanzano P, Deng L, Leibel RL, Rubin M, Nickolas T, Chung W, Zeltser LM, Williams KW, Pessin JE, Kousteni S. “MC4R-dependent suppression of appetite by bone-derived lipocalin 2.” Nature. 2017 Mar 16; 543(7645): 385-390.

Tech Ventures Reference:

• IR CU23375

• Licensing Contact: Jerry Kokoshka