Use Of Polyinosinic-polycytidylic Acid Compositions In Treatment Of Malignant Effusion

• US 20190328767A1
• Filed: 09/26/2017
• Published: 10/31/2019
• Est. Priority Date: 09/30/2016
• Status: Active Grant

• Current Assignee: Biosyngen Pte., Ltd.
• Original Assignee: Biosyngen Pte., Ltd.
• Inventors: YE, Sheng
• Granted Patent: US 11,020,419 B2
• Time in Patent Office: 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 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/14 Alkali metal chlorides; Alkaline earth metal chlorides
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07H 21/02 with ribosyl as saccharide radical

Abstract

The use of an immunomodulating composition comprising polyinosinic:polycytidylic acid (PIC) in the treatment or prevention of malignant effusion, or the alleviation of symptoms of malignant effusion. The composition may further comprise a stabilizer and/or calcium ion, anti-cancer agent, an antigen or any pharmaceutically acceptable carriers.

Claims

1. An immunomodulating composition comprising polyinosinic:

polycytidylic acid (PIC) for use in the treatment of malignant effusion.

3. The composition of claim 1, further comprising calcium ions, wherein the source of calcium ions is preferably calcium chloride (CaCl₂).

7. The composition of claim 1, wherein the PIC is a polyriboinosinic-polyribocytidylic acid.

8. The composition of claim 1, comprising a) polyinosinic:

polycytidylic acid (PIC);

b) Kanamycin; and

c) calcium chloride (CaCl₂).

9. The composition of claim 1, further comprising a pharmaceutically acceptable vector (s), adjuvant(s), excipient (s), diluent (s).

10. The composition of claim 1, further comprising a pharmaceutically acceptable vector(s), adjuvant (s), excipient (s), or diluent (s).

11. The composition of claim 1, further comprising an antigent (s), wherein the antigen is selected from the tumor antigen, cancer neoantigen, plant antigen, animal antigen, microbial antigen, or viral antigen.

12. The composition of claim 1, wherein the composition is to be administered by parenteral administration, intramuscular injection, intraperitoneal perfusion, intrapleural perfusion, intravenous perfusion, subcutaneous injection, intrapericardial injection, inhalation, endorectral perfusion, suppository, intra nasal, ophtalmic, transdermal or oral administration.

13. The composition of claim 1, wherein the malignant effusion arises from a primary tumor originating in the lung, lymph, liver, stomach, colon, breast, ovary, pancreas, biliary duct, esophagus, brain, nose or prostrate gland.

14. The composition of claim 1, wherein the malignant effusion is located in the pleural cavity and arises from the metastases of the lung cancer, lymphoma, stomach cancer, colon cancer, breast cancer or ovary cancer.

15. The composition of claim 1, wherein the malignant effusion is located in the peritoneal cavity and arises from the metastases of the ovary cancer, pancreatic cancer, biliary duct cancer, or esophagus cancer.

16. The composition of claim 1, wherein the said malignant effusion is selected from malignant pleural effusion, malignant ascites or malignant pericardial effusion.

17. The composition of claim 1, wherein

a) the amount of PIC is 0.1 to 10.0 g/L;

and/or

b) the amount of kanamycin is 100 to 5000 IU per 1.0 mg of PIC; and

/or

c) the amount of calcium chloride is 0.2 to 4.0 mmol/L.

18. The composition of claim 11, wherein the composition is to be administered during and/or via a chest drainage, thoracentesis, temporary or permanent pleural catheter insertion, thoracoscopic pleurodesis, pericardial intraluminal stenting or fenestrated drainage, or surgical shunting procedure.

19. The composition of claim 1, wherein the subject is at risk of developing malignant effusion.

20. The composition of claim 1, wherein the composition modulates the immune response of the subject to prevent, reduce or alleviate malignant effusion.

21. The composition of claim 1, wherein the subject has maligant effusion.

22. The use of a composition according to claim 1 for the manufacture of a medicament for the treatment of malignant effusion.

23. A method of treating maligant effusion in a subject, wherein the method comprises a composition according to claim 1 for administration to a subject.

2. An immunomodulating composition comprising polyinosinic:

polycytidylic acid (PIC) and at least one stabilising agent, for use in the of treatment of maligant effusion.

4. The composition of claim 2, wherein the stabilising agent is an aminoglycoside or non-aminoglycoside amine.

5. The composition of claim 4, wherein the aminoglycoside is selected from the group consisting of Dihydrostreptomycin, Mannosidostreptomycin, Amikacin, Butyrosin, Debekacin, Destomycin, Gentamicin, Kanamycin, Lividomycin, Netilmicin, Neomycin, Paromomycin, Ribostamycin, Sisomicin, Streptomycin, Streptothricin, Tobramycin and Validamycin.

6. The composition of claim 5, wherein the aminoglycoside is Kanamycin.