US 2003/0165466 A1Published application

Recombinant poliovirus for the treatment of cancer

AssigneeThe Research Foundation of State University of New York

InventorsMatthias Gromeier, Eckard Wimmer

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Abstract

The present invention is directed to non-pathogenic, oncolytic, recombinant polioviruses for the treatment of various forms of malignant tumors. The recombinant polioviruses of the invention are those in which the internal ribosomal entry site (IRES) of the wild type poliovirus was exchanged with the IRES of other picornaviruses, and optionally P1, P3 or the 3′NTR thereof was exchanged with that of poliovirus Sabin type. More particularly, the present invention is directed to the administration of the non-pathogenic, oncolytic, recombinant poliovirus to the tumor directly, intrathecally or intravenously to cause tumor necrosis. The method of the present invention is particularly useful for the treatment of malignant tumors in various organs, such as: breast, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain. Astounding remissions in experimental animals have been demonstrated for the treatment of malignant glioblastoma multiforme, an almost universally fatal neoplasm of the central nervous system.

Claims57

Dependent claims

A recombinant poliovirus constructed from a poliovirus having a 5′NTR region containing an internal ribosomal entry site (IRES), and the coding sequences for structural proteins (P1), and for the non-structural proteins (P2 and P3) and a 3′NTR selected from the group consisting of wild type serotype 1, serotype 2, and serotype 3, wherein

a. i. a part of the IRES of the poliovirus is substituted with a part of the IRES of Human Rhinovirus serotype 2 also having a 5′NTR region containing an internal ribosomal entry site (IRES), the coding sequences of structural proteins (P1), and for the non-structural proteins (P2 and P3) and a 3′NTR, or
ii. at least a part of the IRES of the poliovirus is substituted with at least a part of the IRES of a virus selected from the group of picornaviruses comprising Human Rhinovirus serotype 1-100, coxsackievirus serotype B1-B6, human echovirus serotype 1-7, 9, 11-27, and 29-33, also having a 5′NTR region containing an internal ribosomal entry site (IRES), the coding sequences of structural proteins (P1), and for the non-structural proteins (P2 and P3) and a 3′NTR, and wherein
b. optionally, at least a part of the P1 of the poliovirus is substituted with at least a part of the P1 of a Poliovirus (Sabin), selected from the groups consisting of PV1(S), PV2(S) and PV3(S);
c. optionally, at least a part of the P3 of the poliovirus is substituted with at least a part of the P3 of a Poliovirus (Sabin), selected from the groups consisting of PV1(S), PV2(S) and PV3(S);
and
d. optionally, at least a part of the 3′NTR of the poliovirus is substituted with at least a part of the 3′NTR of a Poliovirus (Sabin), selected from the group consisting of PV1(S), PV2(S), and PV3(S).

3 more elements

A therapeutic method of treating malignant tumors comprising:

A. Preparing a recombinant poliovirus from a poliovirus having a 5′ NTR region containing an internal ribosomal entry site (IRES), and the coding sequences for structural proteins (P1), and for the non-structural proteins (P2 and P3) and a 3′NTR selected from the group consisting of wild type serotype 1, serotype 2, and serotype 3, by
a. substituting at least a part of the IRES of the poliovirus with at least ap art of the IRES of a virus selected from the group of picornaviruses comprising Human Rhinovirus serotype 1, 3-100, coxsackievirus serotype B1-B6, human echovirus serotype 1-7, 9, 11-27, 29-33, also having a 5′NTR region containing an internal ribosomal entry site (IRES), the coding sequences of structural proteins (P1), and for the non-structural proteins (P2 and P3) and a 3′NTR, and wherein
b. optionally, substituting at least a part of the P1 of the poliovirus with at least a part of the P1 of a Poliovirus (Sabin), selected from the groups consisting of PV1(S), PV2(S) and PV3(S);
c. optionally, substituting at least a part of the P3 of the poliovirus with at least a part of the P3 of a Poliovirus (Sabin), selected from the groups consisting of PV1(S), PV2(S) and PV3(S);
d. optionally, substituting at least a part of the 3′NTR of the poliovirus with at least a part of the 3′NTR of a Poliovirus (Sabin), selected from the group consisting of PV1(S), PV2(S), and PV3(S);
and
B. Administering directly to the tumor site, intrathecally or intravenously a composition comprising the recombinant poliovirus.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/175,247Filed 19 Jun 2002
Priority: 5 Aug 1998
Published: 4 Sep 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C12N 15/86
For animal cells: viral vectors
A61K 35/768
Viruses; Subviral particles; Bacteriophages: oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
A61P 35/00
Antineoplastic agents
A61P 35/04
Antineoplastic agents: specific for metastasis

Family

Application09/129,686Division · filed 5 Aug 1998
Application09/566,581Division · filed 8 May 2000
Application10/175,247Division · filed 19 Jun 2002
US 6,264,940 B1Related patent
US 6,464,972 B1Related patent
US 7,147,848 B2Related patent
US 2003/0165466 A1This patent

From the US filing history. Foreign family members aren’t listed.