Patents & Licensing

PATENT: Using sBCMA to Monitor Myeloma

Circulating B-cell maturation antigen (BCMA) levels are high enough in most MM patients to interfere with anti-BCMA antibody-based treatments from reaching the MM tumor cells.

B cell maturation antigen (BCMA) is a member of the tumor necrosis factor receptor superfamily that plays an important role in regulating B cell proliferation and survival.1 BCMA is expressed on the cell membrane of normal and malignant B lymphocytes and plasma cells, but not other normal tissues.2,3 When bound to its ligands BAFF and APRIL, BCMA delivers pro-survival cell signaling.4

BCMA is central to the survival of multiple myeloma cells.1 BCMA, BAFF, and APRIL are all expressed at significantly higher levels in patients with multiple myeloma than in healthy individuals.1,5 Overexpression leads to upregulation of anti-apoptotic proteins and the survival of multiple myeloma cells.1 Upregulation of BCMA also correlates with disease burden and poor prognosis in multiple myeloma.1

PATENT: Combination of JAKi’s with Immunomodulatory Agents for Anti-cancer Applications

JAK inhibitors (JAKi) have a proven track record in myelofibrosis with an efficacy and safety profile making them attractive in MM.

JAK inhibitors can ‘rescue the response’ in patients who are progressing on immunomodulatory agents.

JAK inhibitors have the benefit of antagonizing the lethargy affects of immunomodulatory agents and make the patients feel better with more energy.

PATENT: Modulating Gamma Secretase Inhibitors (GSIs) to Improve BCMA-targeted Therapies

Gamma secretase (GS) is responsible for shedding of BCMA from the cell surface. GSIs prevent the ‘shedding’ of cellular-bound BCMA.

Therapies targeting BCMA can see their activities modulated (potentially enhanced) by this anti-shedding affect. At very low concentrations, inhibitors of GS block shedding of BCMA from multiple myeloma (MM) cells in vitro resulting in markedly lower supernatant levels of this protein.

References:

1. Cho S-F, Anderson KC, Tai Y-T. Front Immunol. 2018;9:1821.
2. Huang H-W, Chen C-H, Lin C-H, Wong C-H, Lin K-I. Proc Natl Acad Sci U S A. 2013;110(27):10928-109333.
3. Hatzoglou A, Roussel F, Bourgeade M-F, et al. J Immunol. 2000;165(3):1322-1330.
4. Coquery CM, Erickson LD. Crit Rev Immunol. 2012;32(4):287-305.
5. Moreaux J, Legouffe E, Jourdan E, et al. Blood. 2004;103(8):3148-3157.

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