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 The leading web portal for pharmacy resources, news, education and careers July 20, 2018
Pharmacy Choice - Pharmaceutical News - Patent Application Titled "Combination Therapy Using Belinostat and Pralatrexate to Treat Lymphoma" Published Online (USPTO 20180177783) - July 20, 2018

Pharmacy News Article

 7/21/18 - Patent Application Titled "Combination Therapy Using Belinostat and Pralatrexate to Treat Lymphoma" Published Online (USPTO 20180177783)

By a News Reporter-Staff News Editor at Investment Weekly News According to news reporting originating from Washington, D.C., by VerticalNews journalists, a patent application by the inventor Reddy, Guru (Irvine, CA), filed on June 14, 2016, was made available online on July 5, 2018.

The assignee for this patent application is Spectrum Pharmaceuticals Inc.

Reporters obtained the following quote from the background information supplied by the inventors: "Despite years of research into the development of new methods of treatment, cancers of the lymphatic system, or lymphomas, remain quite common. For example, more than 60,000 people in the United States are diagnosed with lymphoma each year, including more than 55,000 cases of non-Hodgkin's lymphoma, and these numbers are constantly increasing.

"Non-Hodgkins lymphoma (NHL) includes several different types of lymphomas, and are typically classified based on whether the tumors arise from B-lymphocytes ('B-cell lymphomas') or from T-lymphocytes ('T-cell lymphomas'). The former make up the majority of NHLs; only about 15% of NHLs are T-cell lymphomas. The majority of T-cell lymphomas are classified as 'peripheral T-cell lymphomas' which arise from mature T-cells. Peripheral T-cell lymphomas include several aggressive subtypes, including, e.g., peripheral T-cell lymphoma not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL); angioimmunoblastic T-cell lymphoma (AITL); cutaneous T-cell lymphoma (CTCL) including, e.g., Sezary Syndrome; enteropathy-type T-cell lymphoma; nasal NK/T-cell lymphoma; and hepatosplenic gamma-delta T-cell lymphoma.

"The prognosis for those affected by NHL is often poor, as the survival rates for lymphoma patients remain low. Traditional treatments for lymphoma typically depend on the type of lymphoma as well as the medical history of the patient. First-line treatment for many lymphomas typically includes chemotherapy. Such chemotherapy will often entail the administration of a 'cocktail' of compounds, e.g., the formulation 'CHOP', which includes cyclophosphamide, doxorubicin, vincristine, and prednisone. In addition, certain first-line cancer treatments also include other forms of cancer therapy, such as radiation therapy.

"In many cases, patients respond initially to first-line treatments, but subsequently suffer a relapse, i.e., a tumor reappears or resumes growing. Following one such relapse, patients are often treated with further chemotherapy, e.g., with 'CHOP' or with other formulations, or, in some cases, the patients are treated with other procedures such as bone marrow transplantation. Again, in many cases, patients initially respond to such additional treatments, but subsequently suffer another relapse. In general, the more relapses a patient suffers, the less agreement there is in the art concerning optimal subsequent treatment. In other cases, a patient fails to respond at all to a treatment, even initially, and is thus said to have a refractory cancer. In such cases as well, little agreement exists in the art regarding optimal subsequent treatment.

"Histone deacetylase (HDAC) inhibitors represent a new mechanistic class of anti-cancer therapeutic. Histones are major protein components of chromatin. The regulation of chromatin structure is understood to be a central mechanism for the control of gene expression. As a general paradigm, acetylation of the epsilon amino groups of lysine residues in the amino-terminal tails of nucleosomal histones is associated with transcriptional activation, while deacetylation is associated with condensation of chromatin and transcriptional repression. Acetylation and deacetylation of histones are controlled by the enzymatic activity of histone acetyltransferases (HATs) and histone deacetylases. Several transcription factors including p53 and GATA-1 have also been shown to be substrates for HDACs.

"HDAC inhibitors have been shown to enhance histone acetylation and induce the expression of genes associated with cell cycle arrest and tumor suppression. Phenotypic changes induced by HDAC inhibitors include G1, and G2/M cell cycle arrest and apoptosis in tumor cells. While data indicate that HDAC inhibitors can arrest growth of cancer cells by inducing apoptosis, promoting differentiation, inhibiting angiogenesis, and/or sensitizing cancer cells to overcome drug resistance, the exact mechanism(s) by which HDAC inhibitors effectively inhibit cancer cell growth is not clearly understood.

"Belinostat (also referred to as PXD-101) is a histone deacetylase inhibitor having the chemical name (2E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide. Belinostat received FDA approval for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma in 2014. It is commercially available for injection in the U.S. under the brand name BELEODAQ.RTM. (Spectrum Pharmaceuticals, Henderson, Nev.).

"In addition to HDAC inhibitors, compounds with antifolate activity can also have therapeutic usefulness as anticancer agents. These agents typically act by inhibiting the activity of dihydrofolate reductase which in turn causes the inhibition of cell division, DNA/RNA synthesis and repair and protein synthesis in rapidly dividing cancer cells. The compound pralatrexate is an antineoplastic folate analog having the chemical name (2S)-2-[4-[(1RS)-1-[(2, 4-diaminopteridin-6-yl)methyl]but-3ynyl]benzoyl]amino]pentanedioic acid. Pralatrexate is currently FDA-approved for the treatment of relapsed or refractory peripheral T-cell lymphoma. It is commercially available for injection in the U.S. under the brand name FOLOTYN.RTM. (Spectrum Pharmaceuticals, Henderson, Nev.)

"As evidenced in the recent FDA approvals of new anti-cancer agents such as belinostat and pralatrexate, great strides have been made in the treatment of cancer. Additional treatment paradigms which produce enhanced therapeutic effects, however, are always desirable."

In addition to obtaining background information on this patent application, VerticalNews editors also obtained the inventor's summary information for this patent application: "The present invention is based upon the unexpected and surprising discovery that the known HDAC inhibitor, belinostat and the antifolate chemotherapeutic agent pralatrexate when used in combination provide unexpectedly greater efficacy than when the anticancer agents are used alone, and specifically, produce synergistic growth inhibitory effects on certain B-cell lymphoma and T-cell lymphoma cell lines.

"Thus, in one aspect, the present invention relates to a method for the treatment of a lymphoma in a patient in need thereof comprising administering to said patient a dosage amount of belinostat and a dosage amount of pralatrexate, wherein the administered amount together comprise a therapeutically effective amount capable of producing a synergistic growth inhibitory effect on the lymphoma. In one embodiment, the lymphoma is a B-cell lymphoma. In a particular embodiment, the B-cell lymphoma is mantle cell lymphoma or diffuse large B-cell lymphoma. In another embodiment, the lymphoma is a T-cell lymphoma. In a particular embodiment, the T-cell lymphoma is a peripheral T-cell lymphoma. In various embodiments, the peripheral T-cell lymphoma is selected from the group consisting of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL); angioimmunoblastic T-cell lymphoma (AITL); cutaneous T-cell lymphoma (CTCL) including, e.g., Sezary Syndrome; enteropathy-type T-cell lymphoma; nasal NK/T-cell lymphoma; and hepatosplenic gamma-delta T-cell lymphoma.

"In another aspect, the invention relates to a pharmaceutical composition comprising belinostat and pralatrexate, and a pharmaceutical carrier or excipient, wherein said composition exhibits a synergistic growth inhibitory effect when used in the treatment of lymphoma.

"In another aspect, the present invention pertains to use of belinostat and pralatrexate in the manufacture of a medicament for the treatment of lymphoma wherein said treatment comprises treatment with a dosage amount of belinostat and a dosage amount of pralatrexate, wherein the administered amount together comprise a therapeutically effective amount capable of producing a synergistic growth inhibitory effect on the lymphoma. In one embodiment, the lymphoma is a B-cell lymphoma. In a particular embodiment, the B-cell lymphoma is mantle cell lymphoma or diffuse large B-cell lymphoma. In another embodiment, the lymphoma is a T-cell lymphoma. In a particular embodiment, the T-cell lymphoma is a peripheral T-cell lymphoma. In various embodiments, the peripheral T-cell lymphoma is selected from the group consisting of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL); angioimmunoblastic T-cell lymphoma (AITL); cutaneous T-cell lymphoma (CTCL) including, e.g., Sezary Syndrome; enteropathy-type T-cell lymphoma; nasal NK/T-cell lymphoma; and hepatosplenic gamma-delta T-cell lymphoma."

For more information, see this patent application: Reddy, Guru. Combination Therapy Using Belinostat and Pralatrexate to Treat Lymphoma. Filed June 14, 2016 and posted July 5, 2018. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220180177783%22.PGNR.&OS=DN/20180177783&RS=DN/20180177783

Keywords for this news article include: Antimetabolites, Antineoplastics, Spectrum Pharmaceuticals Inc, Cancer, Business, Genetics, Oncology, Chromatin, Hematology, Dermatology, Chemotherapy, Nucleoproteins, B-Cell Lymphoma, Sezary Syndrome, Nuclear Proteins, Belinostat Therapy, Cutaneous Lymphoma, Intranuclear Space, Combination Therapy, Drugs and Therapies.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2018, NewsRx LLC



(c) 2018 NewsRx LLC

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