Rna containing compositions and methods of their use

Patent metadata

Field	Value
Publication number	US-2018036334-A1
Application number	US-201615550548-A
Country	US
Kind code	A1
Filing date	Feb 16, 2016
Priority date	Feb 13, 2015
Publication date	Feb 8, 2018
Grant date	—

Abstract

The present invention relates to a composition comprising an isolated, single stranded RNA molecule having a nucleotide sequence comprising 20 or more bases and a pattern of CpG dinucleotides defined by a strength of statistical bias greater than or equal to zero, and a pharmaceutically acceptable carrier suitable for injection. The present invention also relates to a kit comprising a cancer vaccine and the composition of the present invention as an adjuvant to the cancer vaccine. The present invention further relates to a method of treating a subject for a tumor and a method of stimulating an immune response.

First claim

1 . A composition comprising:
an isolated, single stranded RNA molecule having a nucleotide sequence comprising 20 or more bases and a pattern of CpG dinucleotides defined by a strength of statistical bias greater than or equal to zero, and a pharmaceutically acceptable carrier suitable for injection.

2 . The composition according to claim 1 , wherein the strength of statistical bias for the RNA molecule having a nucleotide sequence (x(S 0 )) is determined by maximizing the probability of a sequence (S 0 ) over x, where

P


(

S
|
x

,
m

)

=

1

Z
m



(
x
)



∏

i
=
1

L



f
0



(

s
i

)



exp


(

x




N
m



(
S
)

)

[

EQUATION



1

]

Z
m



(
x
)

=

∑

sequence



S



∏

i
=
1

L



f
0



(

s
i

)



exp


(

xN
m



(
S
)

)

[

EQUATION



2

]

Z m (x) is the normalization constant,
P(S|x, m) is the probability of the sequence given the force (x) and motif m,
x is the force on the motif m that introduces a statistical bias over P,
N m (S) is the number of observed motifs, and
f θ (s i ) is the nucleotide frequencies.

3 . The composition according to claim 1 , wherein the RNA molecule is selected from the group consisting of SEQ ID NOs:1-319, or an immunostimulating fragment thereof.

4 . The composition according to claim 1 , wherein the pharmaceutically acceptable carrier is selected from the group consisting of an emulsion, liposome, microspheres, immune stimulating complex, 900200396.1 nanospheres, montanide, squalene, cyclic dinucleotides, complementary immune modulators, and combinations thereof.

5 . The composition according to claim 1 , wherein the RNA molecule has an immunostimulating effect on tumor cells.

6 . The composition according to claim 1 further comprising:
an antigen-encoding RNA molecule.

7 . The composition according to claim 1 , wherein the RNA molecule is not GSAT.

Assignees

• Icahn School Med Mount Sinai
• Univ Princeton
• Ecole Normale Superieure

Inventors

• Greenbaum Benjamin
• Bhardwaj Nina
• Levine Arnold
• Monasson Remi
• Cocco Simona

Classifications

• G01N33/5011

  for testing antineoplastic activity · CPC title

• A61K31/7105 Primary

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• G01N33/566

  using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds} · CPC title

• C12Q1/68

  involving nucleic acids · CPC title

• C12N15/117

  Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs · CPC title