Use of IAP inhibitor and oncolytic virus in preparation of anti-tumor drug

• US 10,980,850 B2
• Filed: 08/18/2017
• Issued: 04/20/2021
• Est. Priority Date: 08/18/2016
• Status: Active Grant

• Current Assignee: Guangzhou Virotech Pharmaceutical Company Limited
• Original Assignee: Guangzhou Virotech Pharmaceutical Company Limited
• Inventors: Yan, Guangmei, Cai, Jing, Lin, Yuan, Zhang, Haipeng, Lin, Suizhen, Gong, Shoufang, Hu, Jun, Xiao, Xiao, Li, Kai, Liang, Jiankai, Tan, Yaqian, Zhu, Wenbo, Yin, Wei
• Primary Examiner(s): Heyer, Dennis
• Application Number:
  US16/325,974
• Publication Number:
  US 20190167737A1
• Time in Patent Office: 1,341 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 35/768 Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Described herein is use of a Caspase activator and an oncolytic virus in the preparation of an anti-tumor drug. As described, Caspase activator can enhance the anti-tumor effect of oncolytic virus, and the combination of Caspase activator and oncolytic virus produces a significant synergistic anti-tumor effect, and demonstrates an effective therapy for the treatment of tumors that are less sensitive to other pharmaceutical treatments.

Claims

1. A method for treating a solid or hematological tumor in a subject, comprising:

administering to a subject in need thereof at least one of M1 virus or Getah virus; and

enhancing an anti-tumor effect of said M1 or Getah virus comprising administering to the subject in need thereof at least one Inhibitor of Apoptosis (IAP) inhibitor.

2. The method of claim 1, wherein the solid tumor is of a cancer selected from the group consisting of liver cancer, colorectal cancer, bladder cancer, breast cancer, cervical cancer, prostate cancer, glioma, melanoma, pancreatic cancer, nasopharyngeal carcinoma, lung cancer, and gastric cancer.

3. The method of claim 1, wherein the IAP inhibitor is LCL161 or Birinapant, and the LCL161 or Birinapant and said M1 or Getah virus are provided in a ratio of 0.01 to 15 mg:

10³-10⁹ PFU.

4. The method of claim 1, wherein the M1 or Getah virus and IAP inhibitor are provided as a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

5. The method of claim 1, wherein the IAP is at least one selected from the group consisting of cIAP-1, cIAP-2 and XIAP.

6. The method of claim 1, wherein the IAP inhibitor is a Smac protein.

7. The method of claim 1, wherein the TAP inhibitor is used in a range from 0.01 mg/kg to 15 mg/kg, while said M1 virus or Getah virus is used in a titer such that MOI ranges from 10³ to 10⁹ (PFU/kg).

8. The method of claim 1, wherein the TAP inhibitor is used in a range from 0.1 mg/kg to 10 mg/kg, while said M1 virus or Getah virus is used in a titer such that MOI ranges from 10⁵ to 10⁹ (PFU/kg).

9. The method of claim 1, wherein the M1 virus or Getah virus is an M1 virus.

10. The method of claim 1, wherein said M1 virus or Getah virus has a genome as described in Genbank Accession No. EF011023, or has a genome that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, identical to the genomic nucleotide sequence set forth in Genbank Accession No. EF011023.

11. The method of claim 1, wherein said M1 virus or Getah virus has at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% nucleotide sequence identity to the genome of the M1 virus deposited under Accession No. CCTCC V201423.

12. The method of claim 1, wherein said M1 virus or Getah virus has at least 97.8% nucleotide sequence identity to the genome of the M1 virus deposited under Accession No. CCTCC V201423.

13. The method of claim 1, wherein said M1 virus or Getah virus is the M1 virus deposited under Accession No. CCTCC V201423.