Patent
Compositions and methods using siRNA molecules for treatment of gliomas
| العنوان: | Compositions and methods using siRNA molecules for treatment of gliomas |
|---|---|
| Patent Number: | 8,541,568 |
| تاريخ النشر: | September 24, 2013 |
| Appl. No: | 12/994738 |
| Application Filed: | May 26, 2009 |
| مستخلص: | The present invention provides small interfering RNA (siRNA) molecules, compositions containing the molecules, and methods of using the compositions to treat gliomas. |
| Inventors: | Yan, Hai (Durham, NC, US); Lu, Patrick Y. (Rockville, MD, US); Bigner, Darell D. (Durham, NC, US) |
| Claim: | 1. A composition comprising at least three isolated siRNA molecules, wherein at least one isolated siRNA molecule (sense: 5′-CUGUAGACACACCCACCCACAUACA-3′ (SEQ ID NO: 10), antisense: 5′-UGUAUGUGGGUGGGUGUGUCUACAG-3′) (SEQ ID NO: 11) binds to an mRNA molecule that encodes a human VEGF protein and binds to an mRNA molecule that encodes a mouse VEGF protein, at least one isolated siRNA molecule (sense: 5′-CCAUCGAUGUCUACAUGAUCAUGGU-3′ (SEQ ID NO: 14), antisense: 5′-ACCAUGAUCAUGUAGACAUCGAUGG-3′) (SEQ ID NO: 15) binds to an mRNA molecule that encodes a human EGFR protein and binds to an mRNA molecule that encodes a mouse EGFR protein, and at least one isolated siRNA molecule (sense: 5′-GCUGAAGGUUGUGAAAUUCGGAGAA-3′ (SEQ ID NO: 18), antisense: 5′-UUCUCCGAAUUUCACAACCUUCAGC-3′) (SEQ ID NO: 19) binds to an mRNA molecule that encodes a human MGMT protein and binds to an mRNA molecule that encodes a mouse MGMT protein. |
| Claim: | 2. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier. |
| Claim: | 3. The composition of claim 2 , wherein said carrier comprises at least one of the following: a glucose solution, a polycationic binding agent, a cationic lipid, a cationic micelle, a cationic polypeptide, a hydrophilic polymer grafted polymer, a non-natural cationic polymer, a cationic polyacetal, a hydrophilic polymer grafted polyacetal, a ligand functionalized cationic polymer, a ligand functionalized-hydrophilic polymer grafted polymer, and a ligand functionalized liposome. |
| Claim: | 4. The composition of claim 3 , wherein said ligand comprises one or more of an RGD peptide, an RVG peptide, or a FROP peptide. |
| Claim: | 5. The composition of claim 3 , wherein said polymers comprise a biodegradable histidine-lysine polymer, a biodegradable polyester, a polyamidoamine (PAMAM) dendrimer, a cationic lipid, optionally DOTAP, and a PEGylated PEI. |
| Claim: | 6. The composition of claim 2 , wherein said carrier comprises a histidine-lysine copolymer that forms a nanoparticle with the siRNA molecules. |
| Claim: | 7. The composition of claim 1 , further comprising a therapeutic agent that impedes or blocks tumorigenesis, angiogenesis, or cell proliferation in the brain or spinal cord of a mammal. |
| Claim: | 8. The composition of claim 7 , wherein said therapeutic agent is selected from the group consisting of bevacizumab, sunitinib, sorafenib, temsirolimus, and temozolomide. |
| Claim: | 9. A nanoparticle comprising the siRNA molecules of claim 1 , a pharmaceutically acceptable carrier, and a targeting ligand. |
| Claim: | 10. The nanoparticle of claim 9 , wherein said pharmaceutically accepable carrier is a histidine-lysine copolymer. |
| Claim: | 11. The nanoparticle of claim 9 , wherein said targeting ligand is selected from the group consisting of EGF receptor ligands, IL13 ligand, hepatocyte growth factor ligand, single chain monoclonal antibodies, RGD peptide ligands, and RVG peptide ligands. |
| Claim: | 12. The composition of claim 4 wherein said RGD peptide is H-ACRGDMFGCA-OH, said RVG peptide is H-YTIWMPENPRPGTPCDIFTNSRGKRASNG-OH, and said FROP peptide is H-EDYELMDLLAYL-OH. |
| Claim: | 13. The composition of claim 5 wherein said biodegradable polyester comprises poly(lactic acid) (PLA), poly(glycolic acid) (PGA), or poly(lactic-co-glycolic acid) (PLGA). |
| Claim: | 14. The nanoparticle of claim 9 wherein said targeting ligand is an RGD peptide ligand or an RVG peptide ligand. |
| Claim: | 15. The nanoparticle of claim 14 wherein said RGD peptide ligand is a ‘cyclic’ 10mer RGD peptide with the sequence H-ACRGDMFGCA-OH, and -(D)CR(D)WKTCT-(ol). |
| Claim: | 16. The nanoparticle of claim 14 wherein said RVG peptide ligand is YTIWMPENPRPGTPCDIFTNSRGKRASNG or YTIWMPENPRPGTPCDIFTNS-RGKRASNGGGGRRRRRRRRR. |
| Current U.S. Class: | 536/245 |
| Patent References Cited: | 2005/0176024 August 2005 McSwiggen et al. 2006/0121514 June 2006 Young et al. 2006/0134787 June 2006 Zamore et al. 2006/0265765 November 2006 Agatsuma et al. 2007/0003519 January 2007 Lu et al. 2008/0241198 October 2008 Liu et al. 2008/0279920 November 2008 Tang et al. 2010/0319074 December 2010 Lu et al. 2012/0071540 March 2012 Lu et al. WO 0147496 July 2001 WO 03040399 May 2003 WO 03070918 August 2003 WO 03090719 November 2003 WO 2005076999 August 2005 WO 2007079224 July 2007 |
| Other References: | de Wolf et al. (International Journal of Pharmaceutics, 331, 2007, pp. 167-175). cited by examiner Leng et al. (The Journal of Gene Medicine, 2005, 7, pp. 977-986). cited by examiner Michels et al. (Expert Opin. Investig. Drugs, 2006, 15(7), pp. 779-793). cited by examiner Kumar et al., “Transvascular delivery of small interfering RNA to the central nervous system,” Nature, doi:10.1038/nature05901,17 Jun. 2007. cited by applicant International Search Report and Written Opinion of the International Searching Authority of WIPO on International App. No. PCT/US2009/003196 (WO 2009/151539) of Sirnaomics, Inc., Oct. 5, 2009. cited by applicant Cheema, Sangeeta, et al., “Regulation and Guidance of Cell Behavior for Tissue Regeneration Via the Sirna Mechanism”, Wound Repair and Regeneration, vol. 15, No. 3, 2007, pp. 286-295. cited by applicant Pickering, Lulu, “Progress in RNA-based therapeutics,” Spectrum Drug Discovery and Design, Decision Resources, Inc., Waltham, Massachusetts, Aug. 4, 2005, pp. 6-1 to 6-20. cited by applicant Whitmore, Mark, et al., “Synergistic Activation of Innate Immunity by Double-Stranded RNA and CpG DNA Promotes Enhanced Antitumor Activity,” Cancer Research 64, 5850-5860, Aug. 15, 2004. cited by applicant |
| Primary Examiner: | Bowman, Amy |
| Attorney, Agent or Firm: | Karny, Geoffrey M. |
| رقم الانضمام: | edspgr.08541568 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |