Invented by Matthew I. Gross, Susanne M. Steggerda, Weiqun Li, Calithera Biosciences Inc

The market for compositions inhibiting arginase activity has been gaining significant attention in recent years. Arginase is an enzyme that plays a crucial role in the urea cycle, which is responsible for the breakdown of arginine into urea and ornithine. Inhibition of arginase activity has been found to have various therapeutic applications, making it an attractive target for drug development. One of the key areas where compositions inhibiting arginase activity have shown promise is in the treatment of cancer. Arginase plays a role in tumor growth by depleting arginine, an essential amino acid, from the tumor microenvironment. By inhibiting arginase activity, these compositions can restore arginine levels, leading to increased immune response against cancer cells. Several studies have demonstrated the potential of arginase inhibitors in enhancing the efficacy of cancer immunotherapies and inhibiting tumor growth. Another area where compositions inhibiting arginase activity have shown potential is in the treatment of cardiovascular diseases. Arginase has been implicated in the development of endothelial dysfunction, a key factor in the progression of cardiovascular diseases such as atherosclerosis. Inhibiting arginase activity can improve endothelial function by increasing the availability of arginine, which is a precursor for nitric oxide production. Nitric oxide is a potent vasodilator and plays a crucial role in maintaining vascular health. Furthermore, compositions inhibiting arginase activity have also shown promise in the treatment of various inflammatory diseases. Arginase is involved in the regulation of immune responses by modulating the production of inflammatory mediators. Inhibiting arginase activity can reduce the production of pro-inflammatory molecules, thereby alleviating inflammation. This has potential applications in diseases such as asthma, rheumatoid arthritis, and inflammatory bowel disease. The market for compositions inhibiting arginase activity is expected to witness significant growth in the coming years. The increasing prevalence of cancer, cardiovascular diseases, and inflammatory diseases, coupled with the growing understanding of the role of arginase in these conditions, is driving the demand for effective arginase inhibitors. Moreover, advancements in drug discovery and development technologies are facilitating the identification and optimization of novel arginase inhibitors. Several pharmaceutical companies and research institutions are actively involved in the development of compositions inhibiting arginase activity. These companies are investing in research and development activities to identify potent and selective arginase inhibitors. Additionally, collaborations and partnerships between academia and industry are further fueling the progress in this field. In conclusion, the market for compositions inhibiting arginase activity is witnessing significant growth due to their potential therapeutic applications in cancer, cardiovascular diseases, and inflammatory diseases. The demand for effective arginase inhibitors is expected to rise as the understanding of the role of arginase in these conditions continues to expand. With ongoing research and development efforts, the future looks promising for the development of novel arginase inhibitors that can improve patient outcomes and address unmet medical needs.

The Calithera Biosciences Inc invention works as follows

The invention is a method of treating cancer with an arginase inhibitor and a chemotherapeutic drug. The invention also relates to methods for assessing the efficacy of cancer treatments by measuring arginine in a tumour.

Background for Compositions for inhibiting arginase Activity

Cancer is the uncontrolled proliferation of cells within the body that leads to invasion of vital organs and, often, death. In the beginning, pharmacological cancer treatment used non-specific cytotoxic drugs that attacked all rapidly dividing cell types, including normal ones. The non-specific cytotoxic drugs have anti-tumor properties, but are often restricted in their use due to severe side effects. “As our understanding of the proteins, pathways and other factors that allow cancer cells to flourish has developed, more targeted agents that block specific proteins in cancer cells have been developed.

Immuno-oncology is a new field that has emerged to address the challenges of treating cancers. It’s also known as tumor immunology. Certain tumors have developed mechanisms that allow them to avoid destruction by the immune system. Tumor immunology is the field of medicine that focuses on activating your body’s immune system in order to kill and attack tumors. In tumor immunology, the naturally occurring amino acids arginine and lysine are important because they promote growth, survival, and activation of the body’s cancer fighting cytotoxic T cells. Arginase is an enzyme secreted and produced by myeloid-derived suppressor cells that accumulate among cancer patients with multiple histotypes. Arginase levels were elevated in plasma from patients with renal cell carcinoma, breast, chronic myelogenous, lung, esophageal, prostate, glioblastoma and acute myeloid cancer. There is a requirement to develop arginase inhibitors that restore arginine in the tumor microenvironment and promote the tumor-killing ability of cytotoxic cells.

The invention, in certain aspects, provides methods to identify a therapeutic agent that is effective at increasing the level of arginine within a tumor.

a) measuring the first level of arginine within a tumor

b) Contacting the tumor with a therapy agent; and

c) measuring the second level of arginine within the tumor

The therapeutic agent can increase the amount of arginine within the tumor when the second level is higher than the initial level.

In certain aspects, this invention provides methods for identifying a drug that is effective in increasing the level of arginine within a tumor of a subject.

a) measuring the first level of arginine within a tumor in a subject

b) administering a therapeutic agent to the subject; and

c) measuring the second level of arginine within the tumor of the patient;

The therapeutic agent can increase the amount of arginine within the tumor when the second level is higher than the initial level.

In another aspect, the present invention provides a method of assessing a tumor’s response to an agent of therapy arginine, which comprises:

a) measuring the first level of arginine within a tumor from a cancer patient

b) administering an agent of arginine treatment to the patient; and

c) measuring the second level of arginase in the tumor, and assessing the response to the arginine treatment.

The invention also provides methods to assess the anti-cancer efficacy an agent of arginine treatment, which include:

a) measuring the first level of arginine within a tumor from a cancer patient

b) administering an agent of arginine treatment to the patient; and

c) measuring the second level of arginine within the tumor, and thereby assessing anti-cancer efficacy for an agent of arginine treatment.

The invention also provides methods for treating cancer or preventing it, which include administering to the subject a therapeutically-effective amount of an agent of arginase therapy. The arginase inhibitor can be a compound from Formulae I or II. In some embodiments, these methods also include administering additional chemotherapeutic drugs.

Click here to view the patent on Google Patents.