GTC Biotherapeutics (fka GTCB)

[Lewis R Goudy]

Technical brief re CD137 agonist Mabs such as ours

The Tumor Necrosis Factor/Nerve Growth Factor Receptor family of receptors includes two different TNF receptors; nerve growth factor receptor; B cell antigen CD40; T cell antigen OX40; human Fas antigen; and the inducible T cell surface receptor 4-1BB, the human form of which is now referred to as CD137.

CD137 binds with high affinity to a ligand present on antigen-presenting cells, and subsequently interacts with TNF receptor-associated factors (TRAFs) to induce NFkappaB. The ligand for CD137 (CD137L; also referred to as 4-1BBL) is described in U.S. Pat. No. 5,674,704. As shown therein, CD137L is a type II extracellular membrane polypeptide with an intracellular (cytoplasmic) domain at the N-terminus of the polypeptide, followed by a transmembrane region, and an extracellular (receptor-binding) domain at the C-terminus of the polypeptide. Soluble CD137L polypeptides may be derived from the extracellular domain. CD137 is inducible in splenocytes and T cells; the ligand, whose expression is also inducible, is found primarily on antigen presenting cells. Expression of CD137 has also been detected in monocytes, some transformed cells and eosinophils after activation.

The CD137/CD137L interaction appears to play diverse, and sometimes apparently contradictory, roles in various aspects of an immune response. It appears to be important in inhibiting activation-induced cell death in T cells, but abrogates anti-apoptotic effects of other cytokines in neutrophils. CD137 thus may play a role in immune function homeostasis and may represent a target costimulatory system that can be targeted in treatment of cancer or the inflammatory response.

IgE-mediated allergic disorders include asthma, atopic dermatitis and allergy. The etiology of these disorders is complex, but is generally believed to include stimulation of an immune response against an allergen, which is modulated primarily along the TH2 pathway. Numerous cytokines and other agents have been implicated in the development of allergic disorders, including Interleukins 4, 5, 9 and 13. There is extensive interest in developing therapeutic agents that modulate cytokines and other mediators of atopic disease for treatment of these conditions.

SUMMARY OF THE INVENTION
The present invention provides a method for treating a condition mediated by IgE, comprising administering a CD137 agonist to a mammal afflicted with such a condition. In one embodiment, the CD137 agonist is selected from the group consisting of CD137 ligand (CD137L) and agonistic antibodies to CD137. In a particular embodiment the mammal is a human. Conditions mediated by IgE include asthma, atopic dermatitis, allergy, and combinations thereof.

http://www.freshpatents.com/Cd137-agonists-to-treat-patients-with-ige-mediated-conditions-dt20080710ptan20080166336.php?type=description