Methods of treating human papillomavirus

Inventors

Saxena, Shailendra K.Ardelt, Wojciech

Assignees

Orgenesis Inc

Publication Number

US-8663964-B2

Publication Date

2014-03-04

Expiration Date

2031-07-20

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Abstract

Two RNases (ranpirnase and the second embodiment disclosed in U.S. Pat. No. 5,728,805) are tested against human papillomavirus infections. QRT-PCR assays indicate that the RNases have anti-viral activity against type 11 HPV.

Core Innovation

The invention relates to treating human papillomavirus (HPV) infections, particularly type 11 HPV, in living subjects. It specifically involves the use of certain ribonucleases (RNases), namely ranpirnase (ONCONASE) and a close variant referred to as the '805 variant, which differs in three amino acid positions from ranpirnase.

The problem being addressed is the lack of satisfactory treatments for HPV infections. While vaccines like GARDASIL and CERVARIX can prevent HPV infection, infected patients currently have limited treatment options. Existing therapies such as cellular immune inducers and anti-mitotic agents are ineffective against HPV infections, which is concerning due to the risk of progression to cervical cancer.

Ranpirnase and the '805 variant have been found to possess antiviral activity against type 11 HPV, based on quantitative reverse transcriptase PCR (QRT-PCR) assays. These RNases are known to be non-toxic and well-tolerated in humans. The invention provides a method of treatment by administering therapeutically effective amounts of these RNases directly to HPV-infected regions to inhibit virus replication effectively.

Claims Coverage

The patent contains five claims focusing on methods of treating HPV using specific ribonucleases, presenting three main inventive features.

Use of ranpirnase for treating HPV

The method involves directly applying a therapeutically effective amount of ranpirnase to an HPV-infected region of a living subject to treat human papillomavirus infection.

Use of a specific polypeptide variant for treating HPV

The method comprises directly applying a therapeutically effective amount of a polypeptide having the amino acid sequence of SEQ ID NO.: 1 (the '805 variant of ranpirnase) to an HPV-infected region of a living subject for treatment.

Treatment methods specific to type 11 HPV

The method includes the direct application of therapeutically effective amounts of either ranpirnase or the polypeptide with SEQ ID NO.: 1 to regions infected with type 11 HPV in living subjects.

The claims cover methods of treating HPV, including type 11 HPV, through direct application of either ranpirnase or its '805 variant polypeptide, emphasizing the therapeutically effective use of these ribonucleases on HPV-infected regions.

Stated Advantages

Ranpirnase and the '805 variant have strong antiviral activity against type 11 HPV, requiring substantially lower amounts compared to cidofovir to inhibit virus replication by 50%.

The RNases are non-toxic and well-tolerated in humans, making them suitable for therapeutic use.

The selective index (SI) for these RNases indicates effective inhibition of HPV replication without killing infected cells, correlating with potential usefulness in treating living subjects infected with HPV.

Documented Applications

The treatment of human papillomavirus infections, particularly type 11 HPV, in living subjects by direct application of therapeutically effective amounts of ranpirnase or its variant RNase to HPV-infected regions.

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