Process to inhibit or eliminate eosinophilic diseases of the airway and related conditions
AssigneeEmpirico Inc.
InventorsOmri GOTTESMAN, Shannon BRUSE, Brian CAJES, David LEWIS, David ROZEMA
Life of this patent
Estimating the term…
Abstract
Molecules for inhibiting arachidonate 15-lipoxygenase (ALOX-15) gene products including dsRNA (dsRNA) agents such as small interfering RNAs (siRNAs) for therapeutic use, additionally, methods to inhibit the expression of a target gene by administering these agents for the treatment of diseases involving ALOX-15 gene products.
Claims103
A pharmaceutical composition comprising an siRNA molecule comprising a sense strand and an antisense strand, which targets SEQ ID NO:
- 5357 and when administered to a patient in an effective amount reduces eosinophil count, wherein (i) the siRNA comprises a modification comprising a modified nucleoside and/or a modified internucleoside linkage, and/or (ii) the pharmaceutical composition comprises a pharmaceutically acceptable carrier;
- and wherein the patient comprises nasal polyposis, chronic sinusitis, allergic rhinitis, or NSAID-exacerbated respiratory disease, or a combination thereof.
A pharmaceutical composition comprising an siRNA molecule which targets SEQ ID NO:
- 5357 and when administered in an effective amount to a patient comprising nasal polyps, the nasal polyps are reduced in number and/or size the patient, wherein (i) the siRNA comprises a modification comprising a modified nucleoside and/or a modified internucleoside linkage, and/or (ii) the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an siRNA molecule which targets SEQ ID NO:
- 5357 and when administered to a patient in an effective amount increases nasal inspiratory peak flow in the patient, wherein (i) the siRNA comprises a modification comprising a modified nucleoside and/or a modified internucleoside linkage, and/or (ii) the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an siRNA molecule which targets SEQ ID NO:
- 5357 and when administered to a patient in an effective amount reduces airway symptoms in the patient, wherein the patient comprises nasal polyposis, chronic sinusitis, allergic rhinitis, or NSAID-exacerbated respiratory disease, or a combination thereof, and wherein (i) the siRNA comprises a modification comprising a modified nucleoside and/or a modified internucleoside linkage, and/or (ii) the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an siRNA molecule which targets SEQ ID NO:
- 5357 and when administered to a patient in an effective amount improves sense of smell in the patient, wherein the patient comprises nasal polyposis, chronic sinusitis, allergic rhinitis, or NSAID-exacerbated respiratory disease, or a combination thereof, and wherein (i) the siRNA comprises a modification comprising a modified nucleoside and/or a modified internucleoside linkage, and/or (ii) the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an siRNA molecule that inhibits the expression of ALOX15, wherein the siRNA comprises a sense strand and an antisense strand, each strand is independently about 14-30 nucleosides in length, and at least one of the sense strand and the antisense strand comprises a nucleoside sequence comprising about 14-30 contiguous nucleosides of SEQ ID NO:
- 6000 (C AGAGCTGCAG ACCTGGTGTC GAGAGATCAC TGAAATCGGG CTGCAAGGGG CCCAGGACCG AGGGTTTCCT GTCTCTTTAC AGGCTCGGGA CCAGGTTTGC CACTTTGTCA CCATGTGTAT CTTCACCTGC ACCGGCCAAC ACGCCTCTGT);
- wherein (i) the siRNA comprises a modification comprising a modified nucleoside and/or a modified internucleoside linkage, and/or (ii) the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an siRNA molecule that inhibits the expression of ALOX15, wherein the siRNA comprises a sense strand and an antisense strand, each strand is independently about 14-30 nucleosides in length, and at least one of the sense strand and the antisense strand comprises a nucleoside sequence comprising about 14-30 contiguous nucleosides of SEQ ID NO:
- 6003 (A CCCTCTTCCC ATGTCCCACC CTCCCTAGAG GGGCACCTTT TCATGGTCTC TGCACCCAGT GAACACATTT TACTCTAGAG GCATCACCTG GGACCTTACT);
- wherein (i) the siRNA comprises a modification comprising a modified nucleoside and/or a modified internucleoside linkage, and/or (ii) the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an siRNA molecule that inhibits the expression of ALOX15, wherein the siRNA comprises a sense strand and an antisense strand, each strand is independently about 14-30 nucleosides in length, and at least one of the sense strand and the antisense strand comprises a nucleoside sequence comprising about 14-30 contiguous nucleosides of SEQ ID NO:
- 6005 (G ACATGGGAAT TTTCGACCAG ATAATGAGCA CTGGTGGGGG AGGCCACGTG CAGCTGCTCA AGCAAGCTGG AGCCTTCCTA ACCTACAGCT CCTTCTGTCC CCCTGATGAC TTGGCCGACC GGGGGCTCCT GGGAGTGAAG TCTTCCTTCT);
- wherein (i) the siRNA comprises a modification comprising a modified nucleoside and/or a modified internucleoside linkage, and/or (ii) the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising a nucleic acid sequence comprising Formula IA:
- 5′ Z1-U-Z2-G-Z3-U-C-Z4-A-U-U-Z5-L 3′
- wherein
- Z1 is 0, 3, 5, 11, or 13 nucleosides;
- Z2 is 1 nucleoside;
- Z3 is 0, 2, 5, 8, or 10 nucleosides;
- Z4 is 0, 2, 3, 5, 8, or 11 nucleosides;
- Z5 is 0 or 3 nucleosides;
- each “-” is independently a phosphodiester or modified internucleoside linkage;
- and
- L is an optional lipid;
- wherein the nucleic acid comprises a modified nucleoside and/or modified internucleoside linkage.
A pharmaceutical composition comprising a nucleic acid sequence comprising Formula IB:
- 5′ U-Z6-G-A-Z7-C-Z8-A-Z9-U-U 3′
- wherein
- Z6 represents 0, 2, 3, 5, 8, or 11 nucleosides;
- Z7 represents 0, 2, 5, 8, or 10 nucleosides;
- Z8 represents 1 nucleoside;
- Z9 represents 0, 3, 5, 11, or 13 nucleosides;
- and
- each “-” is independently a phosphodiester or modified internucleoside linkage.
A pharmaceutical composition comprising a sense strand and an antisense strand, wherein
- (i) the sense strand comprises SEQ ID NO:
- 3027 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 3028 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (ii) the sense strand comprises SEQ ID NO:
- 5664 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5765 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iii) the sense strand comprises SEQ ID NO:
- 5866 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5967 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iv) the sense strand comprises SEQ ID NO:
- 5558 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5559 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- or
- (v) the sense strand comprises SEQ ID NO:
- 5456 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5457 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions.
A pharmaceutical composition comprising a sense strand and an antisense strand, wherein
- (i) the sense strand comprises SEQ ID NO:
- 3037 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 3038 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (ii) the sense strand comprises SEQ ID NO:
- 5665 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5766 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iii) the sense strand comprises SEQ ID NO:
- 5867 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5968 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iv) the sense strand comprises SEQ ID NO:
- 5560 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5561 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- or
- (v) the sense strand comprises SEQ ID NO:
- 5460 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5461 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions.
A pharmaceutical composition comprising a sense strand and an antisense strand, wherein
- (i) the sense strand comprises SEQ ID NO:
- 3183 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 3184 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (ii) the sense strand comprises SEQ ID NO:
- 5666 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5767 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iii) the sense strand comprises SEQ ID NO:
- 5868 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5969 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iv) or the sense strand comprises SEQ ID NO:
- 5562 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5563 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- or
- (v) the sense strand comprises SEQ ID NO:
- 5476 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5477 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions.
A pharmaceutical composition comprising a sense strand and an antisense strand, wherein
- (i) the sense strand comprises SEQ ID NO:
- 4265 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 4266 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (ii) the sense strand comprises SEQ ID NO:
- 5667 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5768 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iii) the sense strand comprises SEQ ID NO:
- 5869 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5970 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iv) the sense strand comprises SEQ ID NO:
- 5564 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5565 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- or
- (v) the sense strand comprises SEQ ID NO:
- 5510 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5511 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions.
A pharmaceutical composition comprising a sense strand and an antisense strand, wherein
- (i) the sense strand comprises SEQ ID NO:
- 2629 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 2630 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (ii) the sense strand comprises SEQ ID NO:
- 5668 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5769 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iii) the sense strand comprises SEQ ID NO:
- 5870 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5971 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- (iv) the sense strand comprises SEQ ID NO:
- 5566 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5567 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions;
- or
- (v) the sense strand comprises SEQ ID NO:
- 5524 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions, and the antisense strand comprises SEQ ID NO:
- 5525 or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions.
A pharmaceutical composition comprising a sense strand and an antisense strand, wherein the sense strand or antisense strand comprises one or more sequences selected from SEQ ID NOS:
- 1-5349, 5366-5971, 6000-6038, 6050-6074;
- or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions.
A pharmaceutical composition comprising a sense strand and an antisense strand, wherein the sense strand or antisense strand comprises one or more sequences comprising the first 19 nucleobases of a sequence selected from SEQ ID NOS:
- 1-5349, 5366-5971, 6000-6038, 6050-6074;
- or a nucleic acid sequence thereof having about 1 or 2 nucleoside substitutions, additions, or deletions.
Dependencies are inferred from the claim text.