IP Library Patent Application 17266241
Patent Application
App. No. 17/266,241

POLYMER NANOPARTICLE COMPOSITION FOR DELIVERING VIRUS, AND PREPARATION METHOD THEREFOR

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Quick Facts
Patent No.
US None
App. No.
17/266,241
Abstract

The present invention relates to: a virus-containing pharmaceutical composition, which comprises, as an active ingredient, a virus for treating or preventing disease; and a preparation method therefor.

Claims (39)

1 . A composition for delivering virus, comprising: virus as effective ingredient;

amphiphilic block copolymer; and salt of polylactic acid;

wherein the virus is entrapped in a nanoparticle structure formed by the amphiphilic block copolymer and the salt of polylactic acid.

2 . The composition for delivering virus of claim 1 , wherein the virus is oncolytic virus.

3 . The composition for delivering virus of claim 2 , wherein the oncolytic virus is one or more selected from the group consisting of adenovirus, vaccinia virus, herpes simplex virus (HSV) and vesicular stomatitis virus (VSV).

4 . The composition for delivering virus of claim 1 , wherein the amphiphilic block copolymer is an A-B type block copolymer comprising a hydrophilic A block and a hydrophobic B block, wherein the hydrophilic A block is one or more selected from the group consisting of monomethoxy polyethylene glycol, monoacetoxy polyethylene glycol, polyethylene glycol, a copolymer of polyethylene and propylene glycol, and polyvinyl pyrrolidone, and the hydrophobic B block is one or more selected from the group consisting of polyester, polyanhydride, polyamino acid, polyorthoester and polyphosphazine.

5 . The composition for delivering virus of claim 4 , wherein a hydroxyl group at the end of the hydrophobic B block is modified by one or more selected from the group consisting of tocopherol, cholesterol, and C 10-24 fatty acid.

6 . The composition for delivering virus of claim 1 , wherein the salt of polylactic acid is one or more selected from the group consisting of the compounds of the following Formulas 1 to 6:

[Formula 1]

RO—CHZ—[A] n —[B] m —COOM

wherein A is —COO—CHZ—; B is —COO—CHY—, —COO—CH 2 CH 2 CH 2 CH 2 CH 2 — or —COO—CH 2 CH 2 OCH 2 —; R is a hydrogen atom, or acetyl, benzoyl, decanoyl, palmitoyl, methyl or ethyl; each of Z and Y is a hydrogen atom, or methyl or phenyl; M is Na, K or Li; n is an integer of from 1 to 30; and m is an integer of from 0 to 20;

[Formula 2]

RO—CHZ—[COO—CHX] p —[COO—CHY′] q —COO—CHZ—COOM

wherein X is methyl; Y′ is a hydrogen atom or phenyl; p is an integer of from 0 to 25, q is an integer of from 0 to 25, with the proviso that p+q is an integer of from 5 to 25; R is a hydrogen atom, or acetyl, benzoyl, decanoyl, palmitoyl, methyl or ethyl; M is Na, K or Li; and Z is a hydrogen atom, methyl or phenyl.;

[Formula 3]

RO—PAD—COO—W—M′

wherein W—M′ is

PAD is selected from the group consisting of D,L-polylactic acid, D-polylactic acid, polymandelic acid, copolymer of D,L-lactic acid and glycolic acid, copolymer of D,L-lactic acid and mandelic acid, copolymer of D,L-lactic acid and caprolactone, and copolymer of D,L-lactic acid and 1,4-dioxane-2-one; R is a hydrogen atom, or acetyl, benzoyl, decanoyl, palmitoyl, methyl or ethyl; and M is independently Na, K or Li;

[Formula 4]

S—O—PAD—COO—Q

wherein S is

L is —NR 1 — or —O—, wherein R 1 is a hydrogen atom or C 1-10 alkyl; Q is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , or —CH 2 C 6 H 5 ; a is an integer of from 0 to 4; b is an integer of from 1 to 10; M is Na, K or Li; and PAD is one or more selected from the group consisting of D,L-polylactic acid, D-polylactic acid, polymandelic acid, copolymer of D,L-lactic acid and glycolic acid, copolymer of D,L-lactic acid and mandelic acid, copolymer of D,L-lactic acid and caprolactone, and copolymer of D,L-lactic acid and 1,4-dioxane-2-one;

wherein R′ is —PAD—O—C(O)—CH 2 CH 2 —C(O)—OM, wherein PAD is selected from the group consisting of D,L-polylactic acid, D-polylactic acid, polymandelic acid, copolymer of D,L-lactic acid and glycolic acid, copolymer of D,L-lactic acid and mandelic acid, copolymer of D,L-lactic acid and caprolactone, and copolymer of D,L-lactic acid and 1,4-dioxane-2-one, M is Na, K or Li; and a is an integer of from 1 to 4;

[Formula 6]

YO—[—C(O)—(CHX) a —O—] m —C(O)—R—C(O)—[—O—(CHX′) b —C(O)—] n —OZ

wherein X and X′ are independently hydrogen, C 1-10 alkyl or C 6-20 aryl; Y and Z are independently Na, K or Li; m and n are independently an integer of from 0 to 95, with the proviso that 5<m+n<100; a and b are independently an integer of from 1 to 6;

and R is —(CH 2 ) k —, C 2-10 divalent alkenyl, C 6-20 divalent aryl or a combination thereof, wherein k is an integer of from 0 to 10.

7 . The composition for delivering virus of claim 6 , wherein the salt of polylactic acid is a compound of the Formula 1 or 2.

8 . The composition for delivering virus of claim 1 , further comprising cationic compound.

9 . The composition for delivering virus of claim 1 , further comprising divalent or trivalent metal ion.

10 . The composition for delivering virus of claim 9 , wherein the divalent or trivalent metal ion is one or more selected from the group consisting of calcium (Ca 2+ ), magnesium (Mg 2+ ), barium (Ba 2+ ), chromium (Cr 3+ ), iron (Fe 3+ ), manganese (Mn 2+ ), nickel (Ni 2+ ), copper (Cu 2+ ), zinc (Zn 2+ ) and aluminum (Al 3+ ).

11 . The composition for delivering virus of claim 9 , wherein the divalent or trivalent metal ion is comprised in form of sulfate salt, chloride salt, carbonate salt, phosphate salt or hydroxide.

12 . A method for preparing a composition for delivering virus according to claim 1 , comprising:

(a) a step of dissolving virus in aqueous solvent;

(b) a step of dissolving each of amphiphilic block copolymer and salt of polylactic acid in organic solvent; and

(c) a step of mixing the solution of the steps (a) and (b) to form an emulsion.

13 . The method for preparing a composition for delivering virus of claim 12 , wherein step (b) further comprises a step of dissolving cationic compound in organic solvent.

14 . The method for preparing a composition for delivering virus of claim 12 , further comprising (d) a step of selectively removing the organic solvent from the emulsion obtained in step (c).

15 . The method for preparing a composition for delivering virus of claim 14 , further comprising (e) a step of adding divalent or trivalent metal ion after step (d).

Assignments (2)
MERGER AND CHANGE OF NAME Recorded Jun 8, 2021
From: SAMYANG BIOPHARMACEUTICALS CORPORATION; SAMYANG HOLDINGS CORPORATION
To: SAMYANG HOLDINGS CORPORATION
Reel/Frame 056471/0578 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 5, 2021
From: CHOI, JOUNG WOO; KIM, SANG HOON; NAM, HYE YEONG; CHO, HELEN; YUN, MIN HYUK; KIM, GOO YOUNG; LEE, SO JIN
To: SAMYANG BIOPHARMACEUTICALS CORPORATION
Reel/Frame 055239/0408 →