Viral vectors and nucleic acids for use in the treatment of ild, pf-ild and ipf
OwnerSebastian Kreuz, Holger Klein +5inventors
InventorsSebastian Kreuz, Holger Klein, Benjamin Strobel, Stephan Klee, Thorsten Lamla, Marc Kaestle, Ludger Ickenstein
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Abstract
Viral vector comprising: a capsid and a packaged nucleic acid, wherein the nucleic acid either augments the miRNA downregulated in a Bleomycin-induced lung fibrosis model or in an AAV-TGF #1-induced lung fibrosis model, or wherein the nucleic acid inhibits the miRNA up-regulated in a Bleomycin-induced lung fibrosis model or in an AAV-TGF #1-induced lung fibrosis model.
Claims56
Viral vector comprising:
- a capsid and a packaged nucleic acid, wherein the packaged nucleic acid codes for one or more miRNAs, wherein the one or more miRNAs comprise the miRNA of Seq ID No. 15 or a fragment thereof having the sequence of Seq ID No. 99.
Viral vector comprising:
- a capsid and a packaged nucleic acid, wherein the packaged nucleic acid codes for two or more miRNAs,
- (i) wherein the two or more miRNAs comprise the miRNA of Seq ID No. 15 or a fragment thereof having the sequence of Seq ID No. 99, and the miRNA of Seq ID No. 17 or a fragment thereof having the sequence of Seq ID No. 100, or
- (ii) wherein the two or more miRNAs comprise the miRNA of Seq ID No. 15 or a fragment thereof having the sequence of Seq ID No. 99, and the miRNA of Seq ID No. 19 or a fragment thereof having the sequence of Seq ID No. 101.
AAV vector comprising a vector genome that codes for two or more miRNAs, wherein the two or more miRNAs comprise the miRNA of Seq ID No. 15 or a fragment thereof having the sequence of Seq ID No. 99.
AAV vector comprising a vector genome that codes for two or more miRNAs, wherein the two or more miRNAs comprise the miRNA of Seq ID No. 15 or a fragment thereof having the sequence of Seq ID No. 99 and the miRNA of Seq ID No. 17 or a fragment thereof having the sequence of Seq ID No. 100.
A combination of miRNA mimetics for use in a method of prevention and/or treatment of a fibroproliferative disorder, wherein the combination comprises (i) a mimetic of the miRNA having the sequence of Seq ID No. 15, and (ii) a mimetic of the miRNA having the sequence of Seq ID No. 17 and/or a mimetic of the miRNA having the sequence of Seq ID No. 19.
A miRNA mimetic of miRNA-212-5p for use in a method of prevention and/or treatment of a fibroproliferative disorder, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consist of the sequence of Seq ID No. 15 or Seq ID No. 99, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or Seq ID NO. 99;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or Seq ID NO. 99;
- the oligomer is optionally lipid conjugated to facilitate drug delivery,
- wherein said prevention and/or treatment further comprises the administration of a mimetic of a miRNA having the sequence of Seq ID No. 17 and/or a mimetic of a miRNA having the sequence of Seq ID No. 19.
Use of (i) a miRNA mimetic of a miRNA having the sequence of Seq ID No. 15 and (ii) a miRNA mimetic of a miRNA having the sequence of Seq ID No. 17 and/or a miRNA mimetic of a miRNA having the sequence of Seq ID No. 19 for the manufacture of a medicament for the treatment of a fibroproliferative disorder such as IPF or PF-ILD or ILD.
Pharmaceutical composition comprising a miRNA mimetic of a miRNA having the sequence of Seq ID No. 15 and a miRNA mimetic of a miRNA having the sequence of Seq ID No. 17, and a pharmaceutical-acceptable carrier or diluent.
Pharmaceutical composition comprising a miRNA mimetic of a miRNA having the sequence of Seq ID No. 15 and a miRNA mimetic of a miRNA having the sequence of Seq ID No. 19, and a pharmaceutical-acceptable carrier or diluent.
Pharmaceutical composition comprising a miRNA mimetic of a miRNA having the sequence of Seq ID No. 15 and a miRNA mimetic of a miRNA having the sequence of Seq ID No. 17, and a miRNA mimetic of a miRNA having the sequence of Seq ID No. 19, and a pharmaceutical-acceptable carrier or diluent.
Pharmaceutical composition comprising
- (a) a miRNA mimetic of miRNA 212-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consists of the sequence of Seq ID No. 15 or Seq ID No. 99, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or SEQ ID No. 99;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or SEQ ID No. 99;
- the oligomer is optionally lipid conjugated to facilitate drug delivery;
- and
- (b) a miRNA mimetic of miRNA 181a-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consists of the sequence of Seq ID No. 17 or Seq ID No. 100, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 17 or SEQ ID No. 100;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 17 or SEQ ID No. 100,
- the oligomer is optionally lipid conjugated to facilitate drug delivery;
- and
- (c) a pharmaceutical-acceptable carrier or diluent.
Pharmaceutical composition comprising
- (a) a miRNA mimetic of miRNA 212-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consist of the sequence of Seq ID No. 15 or Seq ID No. 99, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or SEQ ID No. 99;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or SEQ ID No 99;
- and
- the oligomer is optionally lipid conjugated to facilitate drug delivery, and
- (b) a miRNA mimetic of miRNA 181b-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consist of the sequence of Seq ID No. 19 or Seq ID No. 101, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing sequence of Seq ID No. 19 or SEQ ID No 101;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 19 or SEQ ID No 101,
- the oligomer is optionally lipid conjugated to facilitate drug delivery;
- and
- (c) a pharmaceutical-acceptable carrier or diluent.
Pharmaceutical composition comprising
- (a) a miRNA mimetic of miRNA 212-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consist of the sequence of Seq ID No. 15 or Seq ID No. 99, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or SEQ ID No 99;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or SEQ ID No. 99;
- and
- the oligomer is optionally lipid conjugated to facilitate drug delivery, and
- (b) a miRNA mimetic of miRNA 181a-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consist of the sequence of Seq ID No. 17 or Seq ID No. 100, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 17 or SEQ ID No. 100;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 17 or SEQ ID No. 100,
- the oligomer is optionally lipid conjugated to facilitate drug delivery;
- and
- (c) a miRNA mimetic of miRNA 212-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consists of the sequence of Seq ID No. 19 or Seq ID No. 101, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 19 or SEQ ID No. 101,
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 19 or SEQ ID No. 101,
- the oligomer is optionally lipid conjugated to facilitate drug delivery;
- and
- (d) a pharmaceutical-acceptable carrier or diluent.
The pharmaceutical composition according to any of claim of 37 to 45, wherein the miRNA mimetic of miRNA-212-5p is a double-strand miRNA mimetic.
Viral vector comprising:
- a capsid and a packaged nucleic acid, wherein the packaged nucleic acid codes for one or more miRNAs, wherein the one or more miRNAs comprise the miRNA of Seq ID No. 17 or a fragment thereof having the sequence of Seq ID No. 100.
Viral vector comprising:
- a capsid and a packaged nucleic acid, wherein the packaged nucleic acid codes for one or more miRNAs, wherein the one or more miRNAs comprise the miRNA of Seq ID No. 19 or a fragment thereof having the sequence of Seq ID No. 101
A combination of miRNA mimetics for use in a method of prevention and/or treatment of a fibroproliferative disorder, wherein the combination comprises (i) a mimetic of the miRNA having the sequence of Seq ID No. 15, and/or (ii) a mimetic of the miRNA having the sequence of Seq ID No. 17 and/or (iii) a mimetic of the miRNA having the sequence of Seq ID No. 19.
Pharmaceutical composition comprising
- (a) a miRNA mimetic of miRNA 212-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consist of the sequence of Seq ID No. 15 or Seq ID No. 99, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or SEQ ID No 99;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 15 or SEQ ID No. 99;
- or
- the oligomer is optionally lipid conjugated to facilitate drug delivery;
- OR
- (b) a miRNA mimetic of miRNA 181a-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consist of the sequence of Seq ID No. 17 or Seq ID No. 100, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 17 or SEQ ID No. 100;
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 17 or SEQ ID No. 100, or
- the oligomer is optionally lipid conjugated to facilitate drug delivery;
- OR
- (c) a miRNA mimetic of miRNA 212-5p, wherein the miRNA mimetic is or contains an oligomer of nucleotides that consists of the sequence of Seq ID No. 19 or Seq ID No. 101, with the following proviso:
- the oligomer optionally comprises nucleotides with chemical modifications leading to non-naturally occurring nucleotides that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 19 or SEQ ID No. 101,
- the oligomer optionally comprises nucleotide analogues that show the base-pairing behavior at the corresponding position (AU and GC) as determined by the sequence of Seq ID No. 19 or SEQ ID No. 101,
- the oligomer is optionally lipid conjugated to facilitate drug delivery;
- AND
- (e) a pharmaceutical-acceptable carrier or diluent.
Dependencies are inferred from the claim text.