Methods of treating infections originating from viruses in the herpesviridae family

Inventors

Saxena, Shailendra K.Ardelt, Wojciech

Assignees

Orgenesis Inc

Publication Number

US-8518399-B2

Publication Date

2013-08-27

Expiration Date

2030-11-17

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Abstract

Three RNases (ranpirnase, the second embodiment disclosed in U.S. Pat. No. 5,728,805, and recombinant Amphinase-2) are tested against identified herpesviridae infections. With some exceptions, quantitative PCR assays indicate that the RNases have anti-viral activity against many of these viruses.

Core Innovation

The invention relates to treating infections caused by viruses in the herpesviridae family using certain ribonucleases (RNases), specifically ranpirnase, the '805 variant of ranpirnase, and recombinant Amphinase 2 (rAmphinase 2). These RNases have been found to exhibit antiviral activity against many herpesviridae viruses as demonstrated by quantitative PCR assays.

The problem being solved is the inadequacy of existing treatments for herpesviridae infections such as human cytomegalovirus. Current treatments like acyclovir and ganciclovir are either insufficiently active or toxic and poorly tolerated, especially in immune-compromised patients. There is a need for treatments that are less toxic, better tolerated, and more effective.

The invention discovers that ranpirnase, the '805 variant, and rAmphinase 2, previously found to be cytotoxic to certain cancer cells, are surprisingly effective against herpesviridae viruses while being non-toxic and well-tolerated in humans. The invention provides methods of administering therapeutically effective amounts of these RNases to living subjects to treat various herpesviridae infections, offering a potentially improved alternative to existing therapies.

Claims Coverage

The patent includes six independent claims describing methods of treating different herpesviridae infections using specific polypeptides.

Method of treating herpesviridae infections excluding roseolovirus-6A

Administering to a living subject a therapeutically effective amount of a polypeptide consisting of the amino acid sequence disclosed in FIG. 2 of U.S. Pat. No. 5,559,212.

Method of treating herpesviridae infections excluding roseolovirus-6A with '805 variant

Administering to a living subject a therapeutically effective amount of a polypeptide consisting of the amino acid sequence of SEQ ID NO:2 of U.S. Pat. No. 5,728,805.

Method of treating human cytomegalovirus

Administering a therapeutically effective amount of either the polypeptide disclosed in FIG. 2 of U.S. Pat. No. 5,559,212 or the polypeptide of SEQ ID NO:2 of U.S. Pat. No. 5,728,805 to a living subject.

Method of treating roseolovirus-6B

Administering a therapeutically effective amount of either the polypeptide disclosed in FIG. 2 of U.S. Pat. No. 5,559,212 or the polypeptide of SEQ ID NO:2 of U.S. Pat. No. 5,728,805 to a living subject.

Method of treating Epstein-Barr virus

Administering a therapeutically effective amount of either the polypeptide disclosed in FIG. 2 of U.S. Pat. No. 5,559,212 or the polypeptide of SEQ ID NO:2 of U.S. Pat. No. 5,728,805 to a living subject.

Method of treating herpes simplex virus

Administering a therapeutically effective amount of either the polypeptide disclosed in FIG. 2 of U.S. Pat. No. 5,559,212 or the polypeptide of SEQ ID NO:2 of U.S. Pat. No. 5,728,805 to a living subject.

The independent claims cover methods of treating various herpesviridae infections by administering therapeutically effective amounts of specific RNases, namely ranpirnase and the '805 variant, either individually or as specified, demonstrating broad coverage of treatment methods against multiple herpesviridae viruses excluding roseolovirus-6A in some claims.

Stated Advantages

Ranpirnase is known to be non-toxic and well-tolerated in humans, and the other two RNases are believed to share these qualities.

The RNases have antiviral activity against many herpesviridae viruses, including human cytomegalovirus, showing potential for more active treatment options.

The invention provides methods that are less toxic, better tolerated, and more active compared to current treatments using acyclovir and ganciclovir.

Documented Applications

Treatment of infections caused by herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), Karposi's sarcoma (HHV-8), roseolovirus-6B (HHV-6B), and other herpesviridae family viruses.

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