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MCL 1997.0: Corticosteroid Conjugates and Uses Thereof

Martin Teicher, M.D., et al.

Background and Description

This invention involves specific chemical modifications to corticosteroids (also known as glucocorticoids), to overcome certain side effects that are common to this category of drug. Glucocorticoids are commonly used for the treatment of a variety of inflammatory or autoimmune diseases. Approximately 10 million new prescriptions for oral glucocorticoids are written each year in the U.S. alone. The frequency of oral glucocorticoids use has been estimated from community survey data to be 0.5% of the general population and 1.75% of women over the age of 55 years. It has been estimated that 56% - 68% of patients with rheumatoid arthritis receive continuous oral treatment with glucocorticoids. This is a large and very attractive market in which there are no exclusive name-brand drugs due to generic competition. Glucocorticoids are relatively inexpensive drugs, but it is the sheer volume used that is significant overall; the total market size is believed to be about 10 billion U.S. dollars per year.

Corticosteroids act by binding to receptors which then act to modulate gene transcription in target tissues. In spite of their efficacy for specific indications, one well-known drawback of the corticosteroids is that they can penetrate the blood-brain barrier, so that such drugs, administered systemically as well as ocularly or topically, can enter the brain, interact with brain tissue, and cause serious adverse effects such as insomnia, depression, severe nausea, headaches and convulsions. The invention involves specific chemical modifications to corticosteroids, so that the resulting conjugates are peripherally acting steroids with reduced activity in the central nervous system. The compounds of the invention would be new chemical entities that can be used for the treatment of a variety of disorders including autoimmune diseases (e.g., rheumatoid arthritis) or inflammatory diseases.

Potential Commercial Uses

The invention provides structurally modified corticosteroids with altered biodistributions. These compounds will have the significant advantage of reducing the occurrence of adverse reactions associated with this class of drug, particularly including CNS-related side effects. No agent has ever been introduced into this class with an improved side effect profile. If these agents succeed only in minimizing adverse neurological and psychiatric side effects they will be widely prescribed, and will be able to command a much higher price than the available generic glucocorticoids. If these agents succeed in preventing secondary adrenal insufficiency they will be so much safer and easier to prescribe that they will send existing glucorticoids into obsolescence.

The chemical modification embodied in this invention can be applied to existing drugs, or compounds under investigation, to create new chemical entities which retain the anti-inflammatory activity of the original compound without any CNS side effects. All of the glucocorticoids now on the market have generic formulations, and there are no exclusive proprietary agents in this class. There are presently six prescribed systemic glucocorticoids that can be targeted for formulation into non-blood brain barrier permeable derivatives.

Publication and Patent Status

McLean Hospital is the owner of a pending U.S. patent application claiming this invention.

Licenses Available

McLean Hospital is seeking exclusive or non-exclusive licensees for this technology.

For more information, please contact:

Anne Ritter, Licensing Manager
Partners Research Ventures and Licensing
(617) 954-9529