WO1995010307A1 - Radiation sensitization using texaphyrins - Google Patents
Radiation sensitization using texaphyrins Download PDFInfo
- Publication number
- WO1995010307A1 WO1995010307A1 PCT/US1994/011491 US9411491W WO9510307A1 WO 1995010307 A1 WO1995010307 A1 WO 1995010307A1 US 9411491 W US9411491 W US 9411491W WO 9510307 A1 WO9510307 A1 WO 9510307A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- texaphyrin
- radiation
- site
- hydrogen
- alkyl
- Prior art date
Links
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- 206010070834 Sensitisation Diseases 0.000 title description 26
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- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0485—Porphyrins, texaphyrins wherein the nitrogen atoms forming the central ring system complex the radioactive metal
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Definitions
- a radiation sensitizer is an agent used to enhance the effect of radiation therapy. In delivering potentially curative doses of radiation, it is necessary to balance the need for local tumor control with the potential for damage to surrounding normal tissues by the delivered dose of radiation (Bush et al . , 1978) . It is therefore desirable to use the lowest radiation dose consistent with local control .
- One way to achieve this would be to utilize a radiation sensitizing agent to enhance cytotoxicity of delivered radiation to the tumor.
- the texaphyrin may be chosen from those of structure A or B:
- n is a positive integer from 1 to 10
- R d is independently H, alkyl, hydroxyalkyl, saccharide, C (m _ w) H ⁇ (2m+1) _ 2w) 0 w 0 z'
- Texaphyrins of structure B having a substituent on a pyrrole nitrogen are provided as new compositions of matter.
- Table 2 of Example 2 presents a summary of substituents contemplated for this derivatized texaphyrin.
- the pyrrole nitrogen substituent (R ⁇ ) may be alkyl, alkenyl, hydroxyalkyl, or alkoxy group having up to about 3 carbon atoms; with the provision that the substituent has rotational flexibility after the first- bound carbon to allow the rest of the group to be positioned outside the plane of the texaphyrin.
- the pyrrole nitrogen substituent is most preferably a methyl group.
- R 2 -R 4 and Rg-Rg are independently hydrogen, halide other than iodide, hydroxyl, alkyl, aryl, haloalkyl other than iodoalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, aminoalkyl, oxyaminoalkyl, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule or a couple to a site-directing molecule.
- FIG. 8 shows the effect of GdB2T2 2+ on L1210 cell kill. Sensitizer enhancement ratios are plotted versus concentration of GdB2T2 2+ . An SER greater than 1.5 is clinically significant. These data indicate that the effectiveness of GdB2T2 2+ as a sensitizer increases with the concentration achieved.
- the present invention involves the use of texaphyrins for radiosensitization in radiation therapy, and for a two-pronged treatment protocol involving radiation therapy and photodynamic tumor therapy. More particularly, the invention demonstrates enhanced cytotoxicity from radiation and enhanced nucleic acid strand scission in the presence of a texaphyrin. Examples 1-4 describe the synthesis of preferred texaphyrins and texaphyrins conjugated to site-directing molecules. Examples 5-8 describe the use of texaphyrins for radiosensitization, radiation therapy and radiation therapy with photodynamic tumor therapy.
- the present example provides synthetic procedures where a texaphyrin is coupled to an oligonucleotide or analog thereof, or is incorporated into the synthesis scheme of an oligonucleotide or analog thereof, to provide a texaphyrin-oligonucleotide or texaphyrin- oligonucleotide analog conjugate having binding specificity for a complementary oligonucleotide.
- the phosphorus (III) is oxidized to the more stable phosphorus (V) state by a short treatment with iodine solution. Unreacted residues are capped with acetic anhydride, the 5'- protective group is removed with weak acid, and the cycle may be repeated to add a further residue until the desired DNA polymer is synthesized. The full length polymer is released from the solid support, with concomitant removal of remaining protective groups, by exposure to base.
- a common protocol uses saturated ethanolic ammonia.
- a metal-texaphyrin complex 3A 2 is attached to a solid support 3A 1 via a six carbon amine linker. This amide-forming coupling reaction is currently employed to attach the complex post-synthetically. It is important to note that texaphyrin hydroxyl groups are protected as an ester on 3A 3 for stepwise synthesis. These protecting groups are labile to the ethanolic ammonia treatment. Such a metal- texaphyrin-derivatized support may be used for stepwise synthesis, and upon cleavage and deprotection, results in a 3'-linked metal-texaphyrin-DNA conjugate 3A 4 .
- the monoconjugate may then be further coupled to nucleotides to produce a texaphyrin-DNA conjugate having the texaphyrin in an internal linkage to the oligonucleotide.
- phosphonate or phosphodiester derivatives of texaphyrin may be utilized to form similar internal, 3', or 5' linkages by the phosphonate or triester methods, respectively.
- texaphyrin causes hydrated electrons to flow to texaphyrin allowing OH* to cause damage.
- texaphyrin radical is relatively stable, yet reacts readily to modify neighboring molecules covalently.
- the SER increases with increasing concentrations of GdT2B2 2+ as indicated in FIG. 8. For example, at 80 ⁇ M, the SER is greater than 2.2, indicating that the highest physiologically tolerable level of GdT2B2 2+ is desirable for radiosensitization purposes.
- Total nucleic acid samples obtained from L1210 cells exposed to a total of 20 Gray radiation and varying levels of GdT2B2 2+ were passed through a size selection filter (one Gray is a unit of absorbed radiation dose equal to 100 rads) . The data of FIG.
- GdT2B2 2+ , GdT2BET 2+ or LuT2BET 2+ texaphyrin for 24 hr at 37°C. After incubation, the cells were harvested, washed, and resuspended in nutrient medium. Aliquots of cell suspensions (5 mL; 5 x 10 5 cells per mL) were placed on sterilized petri dishes and exposed to radiolysis for varying times. The radiation dose was calibrated by Fricke dosimetry. After radiolysis, the cells were incubated at 37°C for 7 days, after which cell viability was assessed by the trypan blue exclusion method. Results were expressed in terms of logarithm of the survival fraction relative to non-irradiated cells. The controls were carried out with cells not exposed to the texaphyrin but irradiated under identical conditions .
- T2B2 gadolinium complex A comparison of the T2B2 gadolinium complex and the T2BET gadolinium complex provided comparable SER results in HT29 cells at all measured concentrations.
- mice with tumors of approximately equal size were selected.
- Gadolinium texaphyrin GdT2BET 2+ (2 ⁇ mol/mL) was administered intravenously by injection in the tail vein. Mice were treated with radiation 2 or 5 hours later.
- a single dose of 10, 20, 30, 40 or 50 Gray of radiation was administered.
- Six studies were run, averaging 4 test animals in each control and dosage group. Mortality and disease-free survival data were acquired as well as periodic measurements of tumor size for up to 75 days following radiation therapy. Kaplan-Meier survival curves were plotted and p-values were determined by log rank analyses of the curves .
- GdT2BET 2+ Although GdT2BET 2+ has light-absorbing capabilities in the visible portion of its electronic spectra (major absorption peaks at about 415, 473, and 739 nanometers) , it is not a photosensitizer because the Gd unpaired electrons immediately quench the excited state of the organic ligand induced by light. Free base texaphyrins or texaphyrins complexed with diamagnetic metals are photosensitive and generate singlet oxygen upon photoirradiation.
- texaphyrins are radiation sensitizers, radiation is more effective and lower doses of radiation may be used, therefore fewer side effects are experienced; and iv) a metal complex is not necessary for radiosensitization.
Abstract
Description
Claims
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE69432221T DE69432221T2 (en) | 1993-10-12 | 1994-10-12 | TEXAPHYRINE AS A SENSITIZER FOR RADIATION |
JP51197695A JP3596816B2 (en) | 1993-10-12 | 1994-10-12 | Radiosensitization using texaphyrin |
CA002173319A CA2173319C (en) | 1993-10-12 | 1994-10-12 | Radiation sensitization using texaphyrins |
NZ275217A NZ275217A (en) | 1993-10-12 | 1994-10-12 | Texaphyrin derivatives and their use as radiation sensitisers |
EP94931812A EP0724457B1 (en) | 1993-10-12 | 1994-10-12 | Radiation sensitization using texaphyrins |
SI9430442T SI0724457T1 (en) | 1993-10-12 | 1994-10-12 | Radiation sensitization using texaphyrins |
DK94931812T DK0724457T3 (en) | 1993-10-12 | 1994-10-12 | Radiation sensitization using texaphyrins |
AU80756/94A AU683316B2 (en) | 1993-10-12 | 1994-10-12 | Radiation sensitization using texaphyrins |
AT94931812T ATE233575T1 (en) | 1993-10-12 | 1994-10-12 | TEXAPHYRINE AS A RADIATION SENSITIZER |
NO19961436A NO315185B1 (en) | 1993-10-12 | 1996-04-11 | Use of Gd and Lu texaphyrins in the preparation of a pharmaceutical composition for use as an irradiation sensitizer |
US08/775,261 US5969111A (en) | 1994-04-14 | 1997-02-04 | Texaphyrins substituted with imidazole are provided |
US08/970,864 US6069140A (en) | 1992-01-21 | 1997-11-14 | Pharmaceutical compositions comprising texaphyrins |
US09/104,870 US6072038A (en) | 1992-01-21 | 1998-06-25 | Conjugates of texaphyrins |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US08/135,118 | 1993-10-12 | ||
US08/135,118 US5457183A (en) | 1989-03-06 | 1993-10-12 | Hydroxylated texaphyrins |
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US08/135,118 Continuation-In-Part US5457183A (en) | 1989-03-06 | 1993-10-12 | Hydroxylated texaphyrins |
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US08/437,968 Continuation US5622946A (en) | 1992-01-21 | 1995-05-10 | Radiation sensitization using texaphyrins |
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WO1995010307A1 true WO1995010307A1 (en) | 1995-04-20 |
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PCT/US1994/011491 WO1995010307A1 (en) | 1992-01-21 | 1994-10-12 | Radiation sensitization using texaphyrins |
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JP (2) | JP3596816B2 (en) |
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AT (1) | ATE233575T1 (en) |
AU (1) | AU683316B2 (en) |
CA (1) | CA2173319C (en) |
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US7449454B2 (en) | 2000-08-30 | 2008-11-11 | Pharmacyclics, Inc. | Metallotexaphyrin derivatives |
US8410263B2 (en) | 2005-09-26 | 2013-04-02 | Pharmacyclics, Inc. | High-purity texaphyrin metal complexes |
Families Citing this family (692)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5252720A (en) * | 1989-03-06 | 1993-10-12 | Board Of Regents, The University Of Texas System | Metal complexes of water soluble texaphyrins |
US5457183A (en) * | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
US5594136A (en) * | 1989-12-21 | 1997-01-14 | Pharmacyclics, Inc. | Texaphyrin solid supports and devices |
US6335434B1 (en) | 1998-06-16 | 2002-01-01 | Isis Pharmaceuticals, Inc., | Nucleosidic and non-nucleosidic folate conjugates |
US8153602B1 (en) | 1991-11-19 | 2012-04-10 | Isis Pharmaceuticals, Inc. | Composition and methods for the pulmonary delivery of nucleic acids |
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US5763172A (en) * | 1992-01-21 | 1998-06-09 | Board Of Regents, The University Of Texas System | Method of phosphate ester hydrolysis |
US5565552A (en) * | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
US5888997A (en) * | 1994-04-14 | 1999-03-30 | Pharmacyclics, Inc. | Radiation sensitization using texaphyrins |
US5607924A (en) * | 1992-01-21 | 1997-03-04 | Pharmacyclics, Inc. | DNA photocleavage using texaphyrins |
US5523389A (en) * | 1992-09-29 | 1996-06-04 | Isis Pharmaceuticals, Inc. | Inhibitors of human immunodeficiency virus |
US5798491A (en) * | 1993-06-09 | 1998-08-25 | Board Of Regents, The University Of Texas System | Multi-mechanistic chemical cleavage using certain metal complexes |
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US5969111A (en) * | 1994-04-14 | 1999-10-19 | Board Of Regents, The University Of Texas System | Texaphyrins substituted with imidazole are provided |
US5633354A (en) * | 1994-09-21 | 1997-05-27 | Pharmacyclics, Inc. | Phosphoramidite derivatives of texaphyrins |
US5837866A (en) * | 1994-09-21 | 1998-11-17 | Board Of Regents, The University Of Texas | Phosphoramidite derivatives of macrocycles |
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US6176842B1 (en) | 1995-03-08 | 2001-01-23 | Ekos Corporation | Ultrasound assembly for use with light activated drugs |
US6420549B1 (en) | 1995-06-06 | 2002-07-16 | Isis Pharmaceuticals, Inc. | Oligonucleotide analogs having modified dimers |
US5714328A (en) * | 1995-06-07 | 1998-02-03 | Board Of Regents, The University Of Texas System | RNA photocleavage using texaphyrins |
RU2106146C1 (en) | 1995-07-17 | 1998-03-10 | Институт элементоорганических соединений РАН | Means to inhibit tumor growth |
US5776925A (en) * | 1996-01-25 | 1998-07-07 | Pharmacyclics, Inc. | Methods for cancer chemosensitization |
US20040266706A1 (en) * | 2002-11-05 | 2004-12-30 | Muthiah Manoharan | Cross-linked oligomeric compounds and their use in gene modulation |
US9096636B2 (en) | 1996-06-06 | 2015-08-04 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds and their use in gene modulation |
US7812149B2 (en) | 1996-06-06 | 2010-10-12 | Isis Pharmaceuticals, Inc. | 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations |
US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
US20030044941A1 (en) | 1996-06-06 | 2003-03-06 | Crooke Stanley T. | Human RNase III and compositions and uses thereof |
DE19641197C2 (en) * | 1996-09-24 | 1999-02-18 | Schering Ag | Ion pairs and their use as contrast agents |
US6525862B2 (en) | 1996-10-30 | 2003-02-25 | Photogen, Inc. | Methods and apparatus for optical imaging |
US6331286B1 (en) | 1998-12-21 | 2001-12-18 | Photogen, Inc. | Methods for high energy phototherapeutics |
US6676626B1 (en) | 1998-05-01 | 2004-01-13 | Ekos Corporation | Ultrasound assembly with increased efficacy |
US6582392B1 (en) * | 1998-05-01 | 2003-06-24 | Ekos Corporation | Ultrasound assembly for use with a catheter |
US5957960A (en) * | 1997-05-05 | 1999-09-28 | Light Sciences Limited Partnership | Internal two photon excitation device for delivery of PDT to diffuse abnormal cells |
AU731909B2 (en) | 1997-07-01 | 2001-04-05 | Isis Pharmaceuticals, Inc. | Compositions and methods for the delivery of oligonucleotides via the alimentary canal |
US6495118B1 (en) * | 1997-09-26 | 2002-12-17 | Schering Aktiengesellschaft | Lipophilic metal complexes for necrosis and infarction imaging |
US6375634B1 (en) | 1997-11-19 | 2002-04-23 | Oncology Innovations, Inc. | Apparatus and method to encapsulate, kill and remove malignancies, including selectively increasing absorption of x-rays and increasing free-radical damage to residual tumors targeted by ionizing and non-ionizing radiation therapy |
US8974363B2 (en) | 1997-12-11 | 2015-03-10 | Provectus Pharmatech, Inc. | Topical medicaments and methods for photodynamic treatment of disease |
DE19824653A1 (en) * | 1998-02-25 | 1999-08-26 | Schering Ag | Use of compounds concentrating in necrotic tissue as drug depots, e.g. for radiation therapy, pharmacotherapy, restenosis prevention and diagnosis |
US20040186071A1 (en) | 1998-04-13 | 2004-09-23 | Bennett C. Frank | Antisense modulation of CD40 expression |
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AU745880B2 (en) * | 1998-05-21 | 2002-04-11 | Isis Pharmaceuticals, Inc. | Compositions and methods for non-parenteral delivery of oligonucleotides |
US6359111B1 (en) * | 1998-05-28 | 2002-03-19 | Neorx Corporation | Opioid receptor targeting |
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US20090117199A1 (en) * | 1998-08-06 | 2009-05-07 | Scott Timothy C | Method of treatment of cancer |
US8557298B2 (en) | 1998-08-06 | 2013-10-15 | Provectus Pharmatech, Inc. | Medicaments for chemotherapeutic treatment of disease |
US6225293B1 (en) | 1998-09-02 | 2001-05-01 | Isis Pharmaceuticals, Inc. | Methods and compounds for tracking the biodistribution of macromolecule-carrier combinations |
US6077709A (en) | 1998-09-29 | 2000-06-20 | Isis Pharmaceuticals Inc. | Antisense modulation of Survivin expression |
US20040047804A1 (en) * | 1998-10-29 | 2004-03-11 | The General Hospital Corporation, A Massachusetts Corporation | Enhanced radiation therapy |
US6986740B2 (en) * | 1998-11-02 | 2006-01-17 | Xantech Pharmaceuticals, Inc. | Ultrasound contrast using halogenated xanthenes |
DE19964220C2 (en) | 1998-11-23 | 2003-07-03 | Friz Biochem Gmbh | Modified nucleic acid oligomer, useful for sequencing by hybridization, is substituted by redox agent to allow electrical detection of hybridization |
US7384623B1 (en) | 1998-12-21 | 2008-06-10 | Provectus Pharmatech, Inc. | High energy phototherapeutic agents |
US8470296B2 (en) * | 1998-12-21 | 2013-06-25 | Provectus Pharmatech, Inc. | Intracorporeal medicaments for high energy phototherapeutic treatment of disease |
US20020001567A1 (en) * | 1998-12-21 | 2002-01-03 | Photogen, Inc. | Intracorporeal medicaments for high energy phototherapeutic treatment of disease |
AU1688099A (en) * | 1998-12-24 | 2000-07-31 | Kyowa Hakko Kogyo Co. Ltd. | Pharmaceutical preparation |
US6300320B1 (en) | 1999-01-05 | 2001-10-09 | Isis Pharmaceuticals, Inc. | Modulation of c-jun using inhibitors of protein kinase C |
DE19901761A1 (en) * | 1999-01-18 | 1999-07-01 | Gerhard Dr Hartwich | Oligonucleotides tagged with photoinducible redox-active unit |
ATE238436T1 (en) * | 1999-01-18 | 2003-05-15 | Friz Biochem Gmbh | METHOD FOR ELECTROCHEMICAL DETECTION OF NUCLEIC ACID OLIGOMER HYBRIDIZATION EVENTS |
US6127124A (en) | 1999-01-20 | 2000-10-03 | Isis Pharmaceuticals, Inc. | Fluorescence based nuclease assay |
US7098192B2 (en) | 1999-04-08 | 2006-08-29 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of STAT3 expression |
US20040229295A1 (en) * | 1999-05-17 | 2004-11-18 | Marchitto Kevin S. | Activated delivery of biomolecules using electromagnetic energy |
US6448239B1 (en) * | 1999-06-03 | 2002-09-10 | Trustees Of Princeton University | Peroxynitrite decomposition catalysts and methods of use thereof |
US6656730B1 (en) | 1999-06-15 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides conjugated to protein-binding drugs |
US7579338B2 (en) * | 1999-10-29 | 2009-08-25 | Pharmacyclics, Inc. | Methods and compositions for treating atheroma, tumors and other neoplastic tissues |
US20030031676A1 (en) * | 1999-10-29 | 2003-02-13 | Pharmacyclics, Inc. | Conjugate compounds for treating atheroma and other diseases |
WO2001032211A2 (en) * | 1999-10-29 | 2001-05-10 | Pharmacyclics, Inc. | Conjugate compounds for treating atheroma and other diseases |
CA2391534A1 (en) * | 1999-11-15 | 2001-05-25 | Drug Innovation & Design, Inc. | Selective cellular targeting: multifunctional delivery vehicles |
US6261840B1 (en) | 2000-01-18 | 2001-07-17 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
US20020055479A1 (en) | 2000-01-18 | 2002-05-09 | Cowsert Lex M. | Antisense modulation of PTP1B expression |
US6607522B1 (en) * | 2000-03-16 | 2003-08-19 | General Hospital Corporation | Methods for tissue welding using laser-activated protein solders |
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CA2429411A1 (en) * | 2000-11-17 | 2002-05-23 | Pharmacyclics, Inc. | Texaphyrin coordination compounds and uses thereof |
US6547812B1 (en) | 2000-12-29 | 2003-04-15 | Advanced Cardiovascular Systems, Inc. | Radiation therapy using a radioactive implantable device and a radiosensitizer agent |
US7767802B2 (en) | 2001-01-09 | 2010-08-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
WO2002059337A1 (en) * | 2001-01-26 | 2002-08-01 | Georgetown University School Of Medicine | Anti-apoptopic gene scc-s2 and diagnostic and therapeutic uses thereof |
AU2002303262A1 (en) * | 2001-04-06 | 2002-10-21 | Georgetown University | Gene shinc-1 and diagnostic and therapeutic uses thereof |
WO2002081639A2 (en) * | 2001-04-06 | 2002-10-17 | Georgetown University | Gene brcc2 and diagnostic and therapeutic uses thereof |
AU2002305151A1 (en) * | 2001-04-06 | 2002-10-21 | Georgetown University | Gene scc-112 and diagnostic and therapeutic uses thereof |
WO2002081642A2 (en) | 2001-04-06 | 2002-10-17 | Georgetown University | Gene brcc-3 and diagnostic and therapeutic uses thereof |
DK2000545T3 (en) | 2001-06-20 | 2011-11-28 | Genentech Inc | Compositions and methods for diagnosis and treatment of lung tumor |
US7803915B2 (en) | 2001-06-20 | 2010-09-28 | Genentech, Inc. | Antibody compositions for the diagnosis and treatment of tumor |
CA2451643C (en) | 2001-06-21 | 2012-11-13 | Isis Pharmaceuticals, Inc. | Antisense modulation of superoxide dismutase 1, soluble expression |
US7425545B2 (en) | 2001-07-25 | 2008-09-16 | Isis Pharmaceuticals, Inc. | Modulation of C-reactive protein expression |
US6964950B2 (en) | 2001-07-25 | 2005-11-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of C-reactive protein expression |
US20030096772A1 (en) | 2001-07-30 | 2003-05-22 | Crooke Rosanne M. | Antisense modulation of acyl CoA cholesterol acyltransferase-2 expression |
US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
US7227014B2 (en) | 2001-08-07 | 2007-06-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein (a) expression |
EP2174953A1 (en) | 2001-09-18 | 2010-04-14 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
US6750019B2 (en) | 2001-10-09 | 2004-06-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of insulin-like growth factor binding protein 5 expression |
NZ566396A (en) | 2001-10-09 | 2009-07-31 | Isis Pharmaceuticals Inc | Antisense modulation of insulin-like growth factor binding protein 5 expressions |
ATE520362T1 (en) | 2001-12-03 | 2011-09-15 | Ekos Corp | CATHETER WITH MULTIPLE ULTRASONIC EMITTING PARTS |
US6965025B2 (en) | 2001-12-10 | 2005-11-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of connective tissue growth factor expression |
US20030130252A1 (en) * | 2001-12-13 | 2003-07-10 | Pharmacyclics, Inc. | Process for affecting neurologic progression |
AU2002367318B2 (en) | 2002-01-02 | 2007-07-12 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
WO2003072581A1 (en) | 2002-02-26 | 2003-09-04 | Board Of Regents, The University Of Texas System | Cyclo[n]pyrroles and methods thereto |
EP1340818A1 (en) * | 2002-02-27 | 2003-09-03 | Epigenomics AG | Method and nucleic acids for the analysis of a colon cell proliferative disorder |
US20030180712A1 (en) | 2002-03-20 | 2003-09-25 | Biostratum Ab | Inhibition of the beta3 subunit of L-type Ca2+ channels |
US8226629B1 (en) | 2002-04-01 | 2012-07-24 | Ekos Corporation | Ultrasonic catheter power control |
US7244565B2 (en) * | 2002-04-10 | 2007-07-17 | Georgetown University | Gene shinc-3 and diagnostic and therapeutic uses thereof |
US7138512B2 (en) * | 2002-04-10 | 2006-11-21 | Georgetown University | Gene SHINC-2 and diagnostic and therapeutic uses thereof |
JP2005536190A (en) | 2002-04-16 | 2005-12-02 | ジェネンテック・インコーポレーテッド | Compositions and methods for tumor diagnosis and treatment |
US20030228317A1 (en) * | 2002-05-22 | 2003-12-11 | Prafulla Gokhale | Gene BRCC-1 and diagnostic and therapeutic uses thereof |
US7199107B2 (en) | 2002-05-23 | 2007-04-03 | Isis Pharmaceuticals, Inc. | Antisense modulation of kinesin-like 1 expression |
US20040019000A1 (en) * | 2002-07-19 | 2004-01-29 | Muthiah Manoharan | Polyalkyleneamine-containing oligomers |
EP2116604A1 (en) | 2002-08-05 | 2009-11-11 | University of Rochester | Protein transducing domain/deaminase chimeric proteins, related compounds, and uses thereof |
US6878805B2 (en) * | 2002-08-16 | 2005-04-12 | Isis Pharmaceuticals, Inc. | Peptide-conjugated oligomeric compounds |
CN1694959B (en) | 2002-09-13 | 2013-09-18 | 雷普利瑟公司 | Non-sequence complementary antiviral oligonucleotides |
US7229976B2 (en) | 2002-09-26 | 2007-06-12 | Isis Pharmaceuticals, Inc. | Modulation of forkhead box O1A expression |
US6921371B2 (en) * | 2002-10-14 | 2005-07-26 | Ekos Corporation | Ultrasound radiating members for catheter |
AU2003287505A1 (en) | 2002-11-05 | 2004-06-03 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds and their use in gene modulation |
US9150605B2 (en) | 2002-11-05 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2′-modified nucleosides for use in gene modulation |
AU2003290598A1 (en) | 2002-11-05 | 2004-06-03 | Isis Pharmaceuticals, Inc. | Modified oligonucleotides for use in rna interference |
US9150606B2 (en) | 2002-11-05 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2'-modified nucleosides for use in gene modulation |
ES2420914T3 (en) | 2002-11-13 | 2013-08-27 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
CA2505801A1 (en) | 2002-11-13 | 2004-05-27 | Rosanne Crooke | Antisense modulation of apolipoprotein b expression |
US8007804B2 (en) | 2002-11-15 | 2011-08-30 | Musc Foundation For Research Development | Complement receptor 2 targeted complement modulators |
CA2506127C (en) | 2002-11-15 | 2013-07-09 | Morphotek, Inc. | Methods of generating high-production of antibodies from hybridomas created by in vitro immunization |
EP2410332A1 (en) | 2002-11-21 | 2012-01-25 | The University Of Utah | Method for identifying purinergic modulators of the olfactory system |
US7144999B2 (en) | 2002-11-23 | 2006-12-05 | Isis Pharmaceuticals, Inc. | Modulation of hypoxia-inducible factor 1 alpha expression |
EP1594459B1 (en) | 2002-12-30 | 2010-02-17 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
CA2514841A1 (en) * | 2003-02-02 | 2004-08-19 | Palo Alto Institute Of Molecular Medicine | Cell-killing molecules and methods of use thereof |
US7468356B2 (en) | 2003-02-11 | 2008-12-23 | Antisense Therapeutics Ltd. | Modulation of insulin like growth factor I receptor expression |
US7803781B2 (en) | 2003-02-28 | 2010-09-28 | Isis Pharmaceuticals, Inc. | Modulation of growth hormone receptor expression and insulin-like growth factor expression |
US20040185559A1 (en) | 2003-03-21 | 2004-09-23 | Isis Pharmaceuticals Inc. | Modulation of diacylglycerol acyltransferase 1 expression |
US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
US7399853B2 (en) | 2003-04-28 | 2008-07-15 | Isis Pharmaceuticals | Modulation of glucagon receptor expression |
WO2005002507A2 (en) | 2003-06-03 | 2005-01-13 | Isis Pharmaceuticals, Inc. | Modulation of survivin expression |
US7786290B2 (en) | 2003-06-13 | 2010-08-31 | Alnylam Pharmaceuticals, Inc. | Double-stranded ribonucleic acid with increased effectiveness in an organism |
US7790691B2 (en) * | 2003-06-20 | 2010-09-07 | Isis Pharmaceuticals, Inc. | Double stranded compositions comprising a 3′-endo modified strand for use in gene modulation |
DE602004030910D1 (en) * | 2003-06-23 | 2011-02-17 | Epigenomics Ag | METHOD AND NUCLEIC ACIDS FOR ANALYZING PROBLEMS OF PROLIFERATION OF COLONOCELLS |
ES2546644T3 (en) | 2003-06-23 | 2015-09-25 | Epigenomics Ag | Methods and nucleic acids for the analysis of proliferative disorders of colorectal cells |
WO2005001141A2 (en) * | 2003-06-23 | 2005-01-06 | Epigenomics Ag | Methods and nucleic acids for analyses of colorectal cell proliferative disorders |
US20040265833A1 (en) * | 2003-06-23 | 2004-12-30 | Cathy Lofton-Day | Methods and nucleic acids for the analysis of colorectal cell proliferative disorders |
CA2533701A1 (en) | 2003-07-31 | 2005-02-17 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding rnas |
WO2005018556A2 (en) | 2003-08-12 | 2005-03-03 | 3M Innovative Properties Company | Hydroxylamine substituted imidazo-containing compounds |
US20060183128A1 (en) * | 2003-08-12 | 2006-08-17 | Epigenomics Ag | Methods and compositions for differentiating tissues for cell types using epigenetic markers |
US7825235B2 (en) | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
RU2006105101A (en) | 2003-08-27 | 2007-10-10 | 3М Инновейтив Пропертиз Компани (US) | Aryloxy and arylalkylene-substituted substituted imidazoquinolines |
AU2004270201A1 (en) | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for CD5+ B cell lymphoma |
US20050053981A1 (en) | 2003-09-09 | 2005-03-10 | Swayze Eric E. | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
AU2004274021B2 (en) | 2003-09-18 | 2009-08-13 | Isis Pharmaceuticals, Inc. | 4'-thionucleosides and oligomeric compounds |
NZ545134A (en) | 2003-09-18 | 2009-06-26 | Lilly Co Eli | Modulation of eIF4E expression |
US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
KR101154101B1 (en) | 2003-10-03 | 2012-06-11 | 쓰리엠 이노베이티브 프로퍼티즈 컴파니 | Alkoxy substituted imidazoquinolines |
EP1678194B1 (en) | 2003-10-10 | 2013-06-26 | Alchemia Oncology Pty Limited | The modulation of hyaluronan synthesis and degradation in the treatment of disease |
CN103495153A (en) | 2003-10-23 | 2014-01-08 | 奇尼塔二有限责任公司 | Method for detecting mutations in a gene associated with resistance to viral infection, OAS1 |
US20050191653A1 (en) | 2003-11-03 | 2005-09-01 | Freier Susan M. | Modulation of SGLT2 expression |
US20070224278A1 (en) | 2003-11-12 | 2007-09-27 | Lyons Robert T | Low immunogenicity corticosteroid compositions |
US20050101582A1 (en) | 2003-11-12 | 2005-05-12 | Allergan, Inc. | Compositions and methods for treating a posterior segment of an eye |
JP2007511527A (en) | 2003-11-14 | 2007-05-10 | スリーエム イノベイティブ プロパティズ カンパニー | Oxime-substituted imidazo ring compounds |
CN1906192A (en) * | 2003-11-14 | 2007-01-31 | 3M创新有限公司 | Hydroxylamine substituted imidazo ring compounds |
ES2493016T3 (en) | 2003-11-17 | 2014-09-11 | Genentech, Inc. | Compositions comprising antibodies against CD79b conjugated to a growth inhibitory agent or a cytotoxic agent and methods for the treatment of tumors of hematopoietic origin |
NZ547467A (en) | 2003-11-25 | 2010-06-25 | 3M Innovative Properties Co | Substituted imidazo ring system and methods |
US9181587B2 (en) * | 2003-12-01 | 2015-11-10 | Epigenomics Ag | Methods and nucleic acids for the analysis of gene expression associated with the development of prostate cell proliferative disorders |
EP1561821B1 (en) | 2003-12-11 | 2011-02-16 | Epigenomics AG | Prognostic markers for prediction of treatment response and/or survival of breast cell proliferative disorder patients |
CA2549852A1 (en) * | 2003-12-11 | 2005-06-30 | Epigenomics Ag | Method and nucleic acids for the improved treatment of breast cell proliferative disorders |
EP1701955A1 (en) | 2003-12-29 | 2006-09-20 | 3M Innovative Properties Company | Arylalkenyl and arylalkynyl substituted imidazoquinolines |
EP1699788A2 (en) | 2003-12-30 | 2006-09-13 | 3M Innovative Properties Company | Imidazoquinolinyl, imidazopyridinyl and imidazonaphthyridinyl sulfonamides |
JP2007518804A (en) | 2004-01-20 | 2007-07-12 | アラーガン、インコーポレイテッド | Composition for topical ophthalmic treatment preferably containing triamcinolone acetonide and hyaluronic acid |
JP2007520222A (en) | 2004-01-20 | 2007-07-26 | アイシス ファーマシューティカルズ インコーポレイテッド | Regulation of glucocorticoid receptor expression |
US7468431B2 (en) | 2004-01-22 | 2008-12-23 | Isis Pharmaceuticals, Inc. | Modulation of eIF4E-BP2 expression |
US20050196466A1 (en) * | 2004-03-02 | 2005-09-08 | Pharmacyclics, Inc. | Process for inhibiting cell proliferation |
US8569474B2 (en) | 2004-03-09 | 2013-10-29 | Isis Pharmaceuticals, Inc. | Double stranded constructs comprising one or more short strands hybridized to a longer strand |
US8790919B2 (en) | 2004-03-15 | 2014-07-29 | Isis Pharmaceuticals, Inc. | Compositions and methods for optimizing cleavage of RNA by RNase H |
US8697873B2 (en) | 2004-03-24 | 2014-04-15 | 3M Innovative Properties Company | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
EP2540734B1 (en) | 2004-04-05 | 2016-03-30 | Alnylam Pharmaceuticals, Inc. | Process and reagents for oligonucleotide synthesis and purification |
US20050244869A1 (en) | 2004-04-05 | 2005-11-03 | Brown-Driver Vickie L | Modulation of transthyretin expression |
US20050260652A1 (en) * | 2004-04-15 | 2005-11-24 | The General Hospital Corporation | Compositions and methods that modulate RNA interference |
US8425929B2 (en) | 2004-04-30 | 2013-04-23 | Allergan, Inc. | Sustained release intraocular implants and methods for preventing retinal dysfunction |
US20050244500A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Intravitreal implants in conjuction with photodynamic therapy to improve vision |
US8119154B2 (en) | 2004-04-30 | 2012-02-21 | Allergan, Inc. | Sustained release intraocular implants and related methods |
EP1750776A2 (en) | 2004-04-30 | 2007-02-14 | Alnylam Pharmaceuticals Inc. | Oligonucleotides comprising a c5-modified pyrimidine |
US7771742B2 (en) | 2004-04-30 | 2010-08-10 | Allergan, Inc. | Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods |
US8722097B2 (en) | 2004-04-30 | 2014-05-13 | Allergan, Inc. | Oil-in-water method for making polymeric implants containing a hypotensive lipid |
US8147865B2 (en) | 2004-04-30 | 2012-04-03 | Allergan, Inc. | Steroid-containing sustained release intraocular implants and related methods |
US8673341B2 (en) | 2004-04-30 | 2014-03-18 | Allergan, Inc. | Intraocular pressure reduction with intracameral bimatoprost implants |
US20050244463A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular vasculopathies |
US20050244458A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Sustained release intraocular implants and methods for treating ocular neuropathies |
US20050244465A1 (en) * | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Drug delivery systems and methods for treatment of an eye |
US7993634B2 (en) | 2004-04-30 | 2011-08-09 | Allergan, Inc. | Oil-in-oil emulsified polymeric implants containing a hypotensive lipid and related methods |
US9498457B2 (en) | 2004-04-30 | 2016-11-22 | Allergan, Inc. | Hypotensive prostamide-containing biodegradable intraocular implants and related implants |
US8591885B2 (en) | 2004-04-30 | 2013-11-26 | Allergan, Inc. | Carbonic anhydrase inhibitor sustained release intraocular drug delivery systems |
US7799336B2 (en) | 2004-04-30 | 2010-09-21 | Allergan, Inc. | Hypotensive lipid-containing biodegradable intraocular implants and related methods |
US8455656B2 (en) | 2004-04-30 | 2013-06-04 | Allergan, Inc. | Kinase inhibitors |
US8512738B2 (en) | 2004-04-30 | 2013-08-20 | Allergan, Inc. | Biodegradable intravitreal tyrosine kinase implants |
EP1765163A1 (en) * | 2004-05-20 | 2007-03-28 | Pharmacyclics, Inc. | A method of enhancing visualization of atherosclerotic plaque |
DK1773872T3 (en) | 2004-05-21 | 2017-05-08 | Uab Res Found | VARIABLE Lymphocyte Receptors, Associated Polypeptides and Nucleic Acids, and Uses thereof |
US8394947B2 (en) | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
US8017779B2 (en) | 2004-06-15 | 2011-09-13 | 3M Innovative Properties Company | Nitrogen containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines |
US7915281B2 (en) | 2004-06-18 | 2011-03-29 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and method |
WO2006009832A1 (en) * | 2004-06-18 | 2006-01-26 | 3M Innovative Properties Company | Substituted imidazo ring systems and methods |
US7897609B2 (en) | 2004-06-18 | 2011-03-01 | 3M Innovative Properties Company | Aryl substituted imidazonaphthyridines |
WO2006009826A1 (en) | 2004-06-18 | 2006-01-26 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines |
US7943308B2 (en) * | 2004-06-23 | 2011-05-17 | Epigenomics Ag | Methods and nucleic acids for the detection of metastasis of colon cell proliferative disorders |
EP1769086A2 (en) | 2004-07-18 | 2007-04-04 | Epigenomics AG | Epigenetic methods and nucleic acids for the detection of breast cell proliferative disorders |
US7427675B2 (en) | 2004-08-23 | 2008-09-23 | Isis Pharmaceuticals, Inc. | Compounds and methods for the characterization of oligonucleotides |
US7884086B2 (en) | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
WO2006032144A1 (en) | 2004-09-23 | 2006-03-30 | Arc Pharmaceuticals, Inc. | Pharmaceutical compositions and methods relating to inhibiting fibrous adhesions or inflammatory disease using fucans from various echinoderm sources |
WO2006034879A2 (en) * | 2004-09-30 | 2006-04-06 | Epigenomics Ag | Epigenetic methods and nucleic acids for the detection of lung cell proliferative disorders |
US20060100190A1 (en) * | 2004-11-05 | 2006-05-11 | Pharmacyclics, Inc. | Motexafin lutetium phototherapy with low fluences for treating vascular inflammation |
US20060099712A1 (en) * | 2004-11-08 | 2006-05-11 | Eastman Kodak Company | Correlation of anti-cancer activity of dyes with redox potentials |
AU2005322435B2 (en) | 2004-12-02 | 2012-02-23 | Epigenomics Ag | Methods and nucleic acids for the analysis of gene expression associated with the prognosis of prostate cell proliferative disorders |
JP5543068B2 (en) | 2004-12-30 | 2014-07-09 | スリーエム イノベイティブ プロパティズ カンパニー | Chiral fused [1,2] imidazo [4,5-c] cyclic compound |
AU2005326708C1 (en) | 2004-12-30 | 2012-08-30 | 3M Innovative Properties Company | Substituted chiral fused [1,2]imidazo[4,5-c] ring compounds |
WO2006084251A2 (en) | 2005-02-04 | 2006-08-10 | Coley Pharmaceutical Group, Inc. | Aqueous gel formulations containing immune reponse modifiers |
US7968563B2 (en) | 2005-02-11 | 2011-06-28 | 3M Innovative Properties Company | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
JP2006224318A (en) * | 2005-02-15 | 2006-08-31 | Brother Ind Ltd | Inkjet recording apparatus |
AU2006223498A1 (en) | 2005-03-10 | 2006-09-21 | Genentech, Inc. | Methods and compositions for modulating vascular integrity |
EP1863814A1 (en) | 2005-04-01 | 2007-12-12 | Coley Pharmaceutical Group, Inc. | 1-substituted pyrazolo (3,4-c) ring compounds as modulators of cytokine biosynthesis for the treatment of viral infections and neoplastic diseases |
US20060223750A1 (en) * | 2005-04-01 | 2006-10-05 | Allergan, Inc. | Agents and methods for enhancing photodynamic therapy |
WO2006107853A2 (en) | 2005-04-01 | 2006-10-12 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridine-1,4-diamines and analogs thereof |
SG183708A1 (en) | 2005-04-15 | 2012-09-27 | Epigenomics Ag | Methods and nucleic acids for analyses of cellular proliferative disorders |
EP1885884A2 (en) | 2005-05-02 | 2008-02-13 | University Of Southern California | DNA METHYLATION MARKERS ASSOCIATED WITH THE CpG ISLAND METHYLATOR PHENOTYPE (CIMP) IN HUMAN COLORECTAL CANCER |
UA95446C2 (en) | 2005-05-04 | 2011-08-10 | Іллюміджен Байосайєнсіз, Інк. | Mutations in oas1 genes |
JP5329949B2 (en) | 2005-05-31 | 2013-10-30 | エコーレ ポリテクニーク フェデラーレ デ ローザンヌ | Triblock copolymers for cytoplasmic delivery of gene-based drugs |
US8252756B2 (en) | 2005-06-14 | 2012-08-28 | Northwestern University | Nucleic acid functionalized nanoparticles for therapeutic applications |
EP1904649A2 (en) * | 2005-07-18 | 2008-04-02 | Epigenomics AG | Compositions and methods for cancer diagnostics comprising pan-cancer markers |
US10053735B2 (en) * | 2005-09-21 | 2018-08-21 | Therawis Diagnostics Gmbh | Markers for the prediction of outcome of anthracycline treatment |
ES2376581T3 (en) * | 2005-09-26 | 2012-03-15 | Pharmacyclics, Inc. | METALLIC COMPLEXES OF ELEVATED PURITY TEXAPHYRINE. |
CN102988368A (en) * | 2005-09-26 | 2013-03-27 | 环状药物公司 | High-purity texaphyrin metal complex |
EP1934369A2 (en) | 2005-09-29 | 2008-06-25 | Epigenomics AG | Methods and nucleic acids for the analysis of gene expression associated with tissue classification |
US20070078119A1 (en) * | 2005-09-30 | 2007-04-05 | Pharmacyclics, Inc. | Storage system for texaphyrin pharmaceutical formulations |
US20080254470A1 (en) * | 2005-10-03 | 2008-10-16 | Epigenomics Ag | Methods and Nucleic Acids For the Analysis of Gene Expression Associated With the Prognosis of Cell Proliferative Disorders |
WO2007042041A1 (en) * | 2005-10-12 | 2007-04-19 | Scanvaegt International A/S | Device for transfer of items |
EP2189522A1 (en) | 2005-10-14 | 2010-05-26 | MUSC Foundation For Research Development | Targeting PAX2 for the induction of DEFB1-mediated tumor immunity and cancer therapy |
US8080534B2 (en) | 2005-10-14 | 2011-12-20 | Phigenix, Inc | Targeting PAX2 for the treatment of breast cancer |
EP2325315B1 (en) | 2005-10-28 | 2014-05-07 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of huntingtin gene |
WO2007056331A2 (en) | 2005-11-09 | 2007-05-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of factor v leiden mutant gene |
US20090197853A1 (en) * | 2005-11-16 | 2009-08-06 | Pharmacyclics, Inc. | Methods and compositions of treating cancer |
EP1966377A2 (en) | 2005-11-21 | 2008-09-10 | Isis Pharmaceuticals, Inc. | Modulation of eif4e-bp2 expression |
US20070219174A1 (en) * | 2006-03-15 | 2007-09-20 | Pharmacyclics, Inc. | Methods of treating cancer using hypofractionated radiation and texaphyrins |
CA2873833A1 (en) | 2006-03-31 | 2007-10-11 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of eg5 gene |
US20090317810A1 (en) * | 2006-04-17 | 2009-12-24 | Epigenomics Ag | Methods and nucleic acids for the detection of colorectal cell proliferative disorders |
EP2013360A2 (en) | 2006-04-17 | 2009-01-14 | Epigenomics AG | Methods and nucleic acids for the detection of colorectal cell proliferative disorders |
WO2007125173A2 (en) | 2006-05-03 | 2007-11-08 | Baltic Technology Development, Ltd. | Antisense agents combining strongly bound base - modified oligonucleotide and artificial nuclease |
US7812150B2 (en) | 2006-05-19 | 2010-10-12 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of Aha and therapeutic uses thereof |
US7888498B2 (en) | 2006-05-22 | 2011-02-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of IKK-B gene |
WO2008097328A2 (en) * | 2006-06-23 | 2008-08-14 | Northwestern University | Asymmetric functionalized nanoparticles and methods of use |
WO2008005631A2 (en) * | 2006-07-07 | 2008-01-10 | Washington State University | Genes encoding chavicol/eugenol synthase from the creosote bush larrea tridentata |
WO2008008432A2 (en) | 2006-07-12 | 2008-01-17 | Coley Pharmaceutical Group, Inc. | Substituted chiral fused( 1,2) imidazo (4,5-c) ring compounds and methods |
US8198253B2 (en) | 2006-07-19 | 2012-06-12 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to HBXIP |
US20110171637A1 (en) * | 2006-07-21 | 2011-07-14 | Reimo Tetzner | Methods and nucleic acids for analyses of cellular proliferative disorders |
ES2546182T3 (en) * | 2006-07-21 | 2015-09-21 | Epigenomics Ag | Methods and kits for methylation analysis in colorectal cell proliferative disorders |
US8133474B2 (en) * | 2006-09-15 | 2012-03-13 | Massachusetts Institute Of Technology | Sensors for fluorescence and magnetic resonance imaging |
WO2008094222A2 (en) * | 2006-10-06 | 2008-08-07 | Trustees Of Princeton | Porphyrin catalysts and methods of use thereof |
EP2104516B1 (en) | 2006-11-01 | 2015-01-07 | University of Rochester | Methods and compositions related to the structure and function of apobec3g |
CA2670144A1 (en) | 2006-11-24 | 2008-05-29 | Epigenomics Ag | Methods and nucleic acids for the analysis of gene expression associated with the development of prostate cell proliferative disorders |
US8969415B2 (en) | 2006-12-01 | 2015-03-03 | Allergan, Inc. | Intraocular drug delivery systems |
CA2672297A1 (en) | 2006-12-11 | 2008-06-19 | University Of Utah Research Foundation | Compositions and methods for treating pathologic angiogenesis and vascular permeability |
US20080164004A1 (en) * | 2007-01-08 | 2008-07-10 | Anastasia Kolesnichenko | Method and system of electromagnetic stirring for continuous casting of medium and high carbon steels |
US10182833B2 (en) | 2007-01-08 | 2019-01-22 | Ekos Corporation | Power parameters for ultrasonic catheter |
US20090203011A1 (en) * | 2007-01-19 | 2009-08-13 | Epigenomics Ag | Methods and nucleic acids for analyses of cell proliferative disorders |
PT2258871E (en) | 2007-01-19 | 2014-08-27 | Epigenomics Ag | Methods and nucleic acids for analyses of cell proliferative disorders |
CA2691066C (en) | 2007-02-09 | 2018-07-31 | Northwestern University | Particles for detecting intracellular targets |
AP3018A (en) | 2007-03-29 | 2014-10-31 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expressionof a gene from the ebola |
EP2826863B1 (en) | 2007-05-30 | 2017-08-23 | Northwestern University | Nucleic acid functionalized nanoparticles for therapeutic applications |
EP2494932B1 (en) | 2007-06-22 | 2020-05-20 | Ekos Corporation | Apparatus for treatment of intracranial hemorrhages |
WO2009006075A2 (en) * | 2007-06-29 | 2009-01-08 | Board Of Regents, The University Of Texas System | Functionalized expanded porphyrins |
WO2009032693A2 (en) | 2007-08-28 | 2009-03-12 | Uab Research Foundation | Synthetic apolipoprotein e mimicking polypeptides and methods of use |
WO2009032702A2 (en) | 2007-08-28 | 2009-03-12 | Uab Research Foundation | Synthetic apolipoprotein e mimicking polypeptides and methods of use |
US8445217B2 (en) | 2007-09-20 | 2013-05-21 | Vanderbilt University | Free solution measurement of molecular interactions by backscattering interferometry |
WO2009039442A1 (en) | 2007-09-21 | 2009-03-26 | California Institute Of Technology | Nfia in glial fate determination, glioma therapy and astrocytoma treatment |
MX2010003465A (en) | 2007-10-02 | 2010-07-05 | Amgen Inc | Increasing erythropoietin using nucleic acids hybridizable to micro-rna and precursors thereof. |
USRE47320E1 (en) | 2007-11-20 | 2019-03-26 | Ionis Pharmaceuticals, Inc. | Modulation of CD40 expression |
US7871985B2 (en) | 2007-12-10 | 2011-01-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of factor VII gene |
AU2008334901A1 (en) | 2007-12-11 | 2009-06-18 | Epigenomics Ag | Methods and nucleic acids for analyses of lung carcinoma |
WO2009079415A1 (en) * | 2007-12-14 | 2009-06-25 | Ekos Corporation | Ultrasound pulse shaping |
CN102014932B (en) | 2008-03-05 | 2015-11-25 | 阿尔尼拉姆医药品有限公司 | For suppressing compositions and the method for Eg5 and VEGF gene expression |
EP2105145A1 (en) * | 2008-03-27 | 2009-09-30 | ETH Zürich | Method for muscle-specific delivery lipid-conjugated oligonucleotides |
WO2009124295A2 (en) | 2008-04-04 | 2009-10-08 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity |
CA2721183C (en) | 2008-04-11 | 2019-07-16 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
US8324366B2 (en) | 2008-04-29 | 2012-12-04 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for delivering RNAI using lipoproteins |
EP3081648A1 (en) | 2008-08-25 | 2016-10-19 | Excaliard Pharmaceuticals, Inc. | Antisense oligonucleotides directed against connective tissue growth factor and uses thereof |
EP2331690B1 (en) | 2008-09-02 | 2016-01-13 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of mutant egfr gene |
EP3587434A1 (en) | 2008-09-23 | 2020-01-01 | Alnylam Pharmaceuticals Inc. | Chemical modifications of monomers and oligonucleotides with click components for conjugation with ligands |
EP2334793B1 (en) | 2008-09-25 | 2016-04-06 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of serum amyloid a gene |
NZ592867A (en) | 2008-10-20 | 2013-05-31 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of transthyretin |
WO2010048585A2 (en) | 2008-10-24 | 2010-04-29 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
KR101967417B1 (en) | 2008-11-10 | 2019-04-10 | 알닐람 파마슈티칼스 인코포레이티드 | Novel lipids and compositions for the delivery of therapeutics |
CA2744207C (en) | 2008-11-24 | 2019-05-28 | Northwestern University | Polyvalent rna-nanoparticle compositions |
US8802074B2 (en) * | 2008-11-26 | 2014-08-12 | Board Of Regents, The University Of Texas System | Polymers functionalized with ion-specific recognition elements |
CA2745811C (en) | 2008-12-04 | 2021-07-13 | Joseph Collard | Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene |
CN102317458B (en) | 2008-12-04 | 2018-01-02 | 库尔纳公司 | Pass through treatment of the suppression of erythropoietin(EPO) (EPO) natural antisense transcript to EPO relevant diseases |
KR101749352B1 (en) | 2008-12-04 | 2017-06-20 | 큐알엔에이, 인크. | Treatment of sirtuin 1(sirt1) related diseases by inhibition of natural antisense transcript to sirtuin 1 |
EP3225281A1 (en) | 2008-12-10 | 2017-10-04 | Alnylam Pharmaceuticals, Inc. | Gnaq targeted dsrna compositions and methods for inhibiting expression |
US20100233270A1 (en) | 2009-01-08 | 2010-09-16 | Northwestern University | Delivery of Oligonucleotide-Functionalized Nanoparticles |
WO2010091308A2 (en) | 2009-02-06 | 2010-08-12 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and methods |
KR101805199B1 (en) | 2009-02-12 | 2017-12-05 | 큐알엔에이, 인크. | Treatment of glial cell derived neurotrophic factor (gdnf) related diseases by inhibition of natural antisense transcript to gdnf |
EP3009150B1 (en) | 2009-02-12 | 2019-11-13 | CuRNA, Inc. | Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf |
US20120041051A1 (en) | 2009-02-26 | 2012-02-16 | Kevin Fitzgerald | Compositions And Methods For Inhibiting Expression Of MIG-12 Gene |
EP3424939A1 (en) | 2009-03-02 | 2019-01-09 | Alnylam Pharmaceuticals Inc. | Nucleic acid chemical modifications |
US20110319317A1 (en) | 2009-03-04 | 2011-12-29 | Opko Curna, Llc | Treatment of sirtuin 1 (sirt1) related diseases by inhibition of natural antisense transcript to sirt1 |
AU2010223967B2 (en) | 2009-03-12 | 2015-07-30 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of Eg5 and VEGF genes |
WO2010107733A2 (en) | 2009-03-16 | 2010-09-23 | Curna, Inc. | Treatment of nuclear factor (erythroid-derived 2)-like 2 (nrf2) related diseases by inhibition of natural antisense transcript to nrf2 |
EP2408920B1 (en) | 2009-03-17 | 2017-03-08 | CuRNA, Inc. | Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1 |
EP3248618A1 (en) | 2009-04-22 | 2017-11-29 | Massachusetts Institute Of Technology | Innate immune suppression enables repeated delivery of long rna molecules |
ES2661787T3 (en) | 2009-05-01 | 2018-04-04 | Curna, Inc. | Treatment of hemoglobin-related diseases (hbf / hbg) by inhibition of natural antisense transcript for hbf / hbg |
CN103223177B (en) | 2009-05-06 | 2016-08-10 | 库尔纳公司 | By suppression therapy lipid transfer and the metabolic gene relevant disease of the natural antisense transcript for lipid transfer and metabolic gene |
KR101722541B1 (en) | 2009-05-06 | 2017-04-04 | 큐알엔에이, 인크. | Treatment of tristetraproline(ttp) related diseases by inhibition of natural antisense transcript to ttp |
CN102575251B (en) | 2009-05-18 | 2018-12-04 | 库尔纳公司 | The relevant disease of the reprogramming factor is treated by inhibiting the natural antisense transcript for the reprogramming factor |
KR101703695B1 (en) | 2009-05-22 | 2017-02-08 | 큐알엔에이, 인크. | Treatment of transcription factor e3 (tfe3) and insulin receptor substrate 2 (irs2) related diseases by inhibition of natural antisense transcript to tfe3 |
EP2435571B1 (en) | 2009-05-28 | 2016-12-14 | CuRNA, Inc. | Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene |
KR101766408B1 (en) | 2009-06-10 | 2017-08-10 | 알닐람 파마슈티칼스 인코포레이티드 | Improved lipid formulation |
EP2443238B1 (en) | 2009-06-16 | 2017-03-22 | CuRNA, Inc. | Treatment of paraoxonase 1 (pon1) related diseases by inhibition of natural antisense transcript to pon1 |
JP5944311B2 (en) | 2009-06-16 | 2016-07-05 | クルナ・インコーポレーテッド | Treatment of collagen gene-related diseases by suppression of natural antisense transcripts against collagen genes |
RU2566724C9 (en) | 2009-06-17 | 2019-03-12 | Байоджен Ma Инк. | Compositions and methods of modulating smn2 splicing in subject |
CN102597238B (en) | 2009-06-24 | 2016-06-29 | 库尔纳公司 | The relevant disease of TNFR2 is treated by suppressing for the natural antisense transcript of tumor necrosis factor receptor 2 (TNFR2) |
WO2010151674A2 (en) | 2009-06-26 | 2010-12-29 | Curna, Inc. | Treatment of down syndrome gene related diseases by inhibition of natural antisense transcript to a down syndrome gene |
EP2966181B1 (en) | 2009-06-26 | 2018-02-14 | Epigenomics AG | Methods and nucleic acids for analysis of bladder carcinoma |
EP2309005B1 (en) | 2009-08-03 | 2015-03-04 | Epigenomics AG | Methods for preservation of genomic DNA sequence complexity |
JP6128848B2 (en) | 2009-08-05 | 2017-05-17 | クルナ・インコーポレーテッド | Treatment of insulin gene (INS) -related diseases by suppression of natural antisense transcripts against the insulin gene (INS) |
EP2464336A4 (en) | 2009-08-14 | 2013-11-20 | Alnylam Pharmaceuticals Inc | Lipid formulated compositions and methods for inhibiting expression of a gene from the ebola virus |
WO2011031482A2 (en) | 2009-08-25 | 2011-03-17 | Curna, Inc. | Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap |
CA2772715C (en) | 2009-09-02 | 2019-03-26 | Genentech, Inc. | Mutant smoothened and methods of using the same |
CN102711826B (en) | 2009-10-22 | 2017-03-29 | 霍夫曼-拉罗奇有限公司 | For the method and composition that the HEPSIN for regulating and controlling macrophage-stimulating albumen is activated |
CA2779099C (en) | 2009-10-30 | 2021-08-10 | Northwestern University | Templated nanoconjugates |
US20110104695A1 (en) | 2009-11-05 | 2011-05-05 | Epigenomics Ag | Methods of predicting therapeutic efficacy of cancer therapy |
NZ716349A (en) | 2009-11-09 | 2017-07-28 | Allergan Inc | Compositions and methods for stimulating hair growth |
CA2781887C (en) | 2009-11-30 | 2018-03-27 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
CA3044884A1 (en) | 2009-12-07 | 2011-06-16 | Arbutus Biopharma Corporation | Compositions for nucleic acid delivery |
WO2011084455A2 (en) | 2009-12-16 | 2011-07-14 | Opko Curna, Llc. | Treatment of membrane bound transcription factor peptidase, site 1 (mbtps1) related diseases by inhibition of natural antisense transcript to mbtps1 |
ES2749426T3 (en) | 2009-12-18 | 2020-03-20 | Univ British Columbia | Nucleic Acid Administration Methods and Compositions |
CN102869776B (en) | 2009-12-23 | 2017-06-23 | 库尔纳公司 | HGF relevant diseases are treated by suppressing the natural antisense transcript of HGF (HGF) |
KR101793753B1 (en) | 2009-12-23 | 2017-11-03 | 큐알엔에이, 인크. | Treatment of uncoupling protein 2 (ucp2) related diseases by inhibition of natural antisense transcript to ucp2 |
EP2519633B1 (en) | 2009-12-29 | 2017-10-25 | CuRNA, Inc. | Treatment of nuclear respiratory factor 1 (nrf1) related diseases by inhibition of natural antisense transcript to nrf1 |
WO2011090741A2 (en) | 2009-12-29 | 2011-07-28 | Opko Curna, Llc | TREATMENT OF TUMOR PROTEIN 63 (p63) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO p63 |
NO2521784T3 (en) | 2010-01-04 | 2018-05-05 | ||
US8912157B2 (en) | 2010-01-06 | 2014-12-16 | Curna, Inc. | Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to a pancreatic developmental gene |
DK2524039T3 (en) | 2010-01-11 | 2018-03-12 | Curna Inc | TREATMENT OF GENDER HORMON-BINDING GLOBULIN (SHBG) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENCE TRANSCRIPTS TO SHBG |
WO2011091390A2 (en) | 2010-01-25 | 2011-07-28 | Opko Curna, Llc | Treatment of rnase h1 related diseases by inhibition of natural antisense transcript to rnase h1 |
WO2011100131A2 (en) | 2010-01-28 | 2011-08-18 | Alnylam Pharmacuticals, Inc. | Monomers and oligonucleotides comprising cycloaddition adduct(s) |
WO2011094580A2 (en) | 2010-01-28 | 2011-08-04 | Alnylam Pharmaceuticals, Inc. | Chelated copper for use in the preparation of conjugated oligonucleotides |
US20130028889A1 (en) | 2010-02-04 | 2013-01-31 | Ico Therapeutics Inc. | Dosing regimens for treating and preventing ocular disorders using c-raf antisense |
WO2011103528A2 (en) | 2010-02-22 | 2011-08-25 | Opko Curna Llc | Treatment of pyrroline-5-carboxylate reductase 1 (pycr1) related diseases by inhibition of natural antisense transcript to pycr1 |
EP2538981B1 (en) | 2010-02-23 | 2017-12-20 | F. Hoffmann-La Roche AG | Compositions and methods for the diagnosis and treatment of tumor |
WO2011105900A2 (en) | 2010-02-23 | 2011-09-01 | Academisch Ziekenhuis Bij De Universiteit Van Amsterdam | Antagonists of complement component 8-alpha (c8-alpha) and uses thereof |
WO2011105902A2 (en) | 2010-02-23 | 2011-09-01 | Academisch Ziekenhuis Bij De Universiteit Van Amsterdam | Antagonists of complement component 8-beta (c8-beta) and uses thereof |
WO2011105901A2 (en) | 2010-02-23 | 2011-09-01 | Academisch Ziekenhuis Bij De Universiteit Van Amsterdam | Antagonists of complement component 9 (c9) and uses thereof |
GB201003630D0 (en) | 2010-03-04 | 2010-04-21 | Novartis Ag | Avian rotavirus |
WO2011112516A1 (en) | 2010-03-08 | 2011-09-15 | Ico Therapeutics Inc. | Treating and preventing hepatitis c virus infection using c-raf kinase antisense oligonucleotides |
WO2011112732A2 (en) | 2010-03-12 | 2011-09-15 | The Brigham And Women's Hospital, Inc. | Methods of treating vascular inflammatory disorders |
ES2893199T3 (en) | 2010-03-29 | 2022-02-08 | Alnylam Pharmaceuticals Inc | dsRNA therapy for transthyretin (TTR)-related ocular amyloidosis |
US9102938B2 (en) | 2010-04-01 | 2015-08-11 | Alnylam Pharmaceuticals, Inc. | 2′ and 5′ modified monomers and oligonucleotides |
US9044494B2 (en) | 2010-04-09 | 2015-06-02 | Curna, Inc. | Treatment of fibroblast growth factor 21 (FGF21) related diseases by inhibition of natural antisense transcript to FGF21 |
US20130260460A1 (en) | 2010-04-22 | 2013-10-03 | Isis Pharmaceuticals Inc | Conformationally restricted dinucleotide monomers and oligonucleotides |
WO2011133871A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | 5'-end derivatives |
US10913767B2 (en) | 2010-04-22 | 2021-02-09 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
WO2011139695A2 (en) | 2010-04-28 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Modified 5' diphosphate nucleosides and oligomeric compounds prepared therefrom |
KR101869570B1 (en) | 2010-04-28 | 2018-06-20 | 아이오니스 파마수티컬즈, 인코포레이티드 | Modified nucleosides and oligomeric compounds prepared therefrom |
EP2625186B1 (en) | 2010-04-28 | 2016-07-27 | Ionis Pharmaceuticals, Inc. | 5' modified nucleosides and oligomeric compounds prepared therefrom |
WO2011139911A2 (en) | 2010-04-29 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Lipid formulated single stranded rna |
WO2011139917A1 (en) | 2010-04-29 | 2011-11-10 | Isis Pharmaceuticals, Inc. | Modulation of transthyretin expression |
EP2566966A4 (en) | 2010-05-03 | 2013-12-11 | Curna Inc | Treatment of sirtuin (sirt) related diseases by inhibition of natural antisense transcript to a sirtuin (sirt) |
MA34291B1 (en) | 2010-05-03 | 2013-06-01 | Genentech Inc | COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING A TUMOR |
TWI586356B (en) | 2010-05-14 | 2017-06-11 | 可娜公司 | Treatment of par4 related diseases by inhibition of natural antisense transcript to par4 |
CA2799207C (en) | 2010-05-26 | 2019-03-26 | Curna, Inc. | Treatment of atonal homolog 1 (atoh1) related diseases by inhibition of natural antisense transcript to atoh1 |
WO2011153323A2 (en) | 2010-06-02 | 2011-12-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods directed to treating liver fibrosis |
US9638632B2 (en) | 2010-06-11 | 2017-05-02 | Vanderbilt University | Multiplexed interferometric detection system and method |
WO2011163121A1 (en) | 2010-06-21 | 2011-12-29 | Alnylam Pharmaceuticals, Inc. | Multifunctional copolymers for nucleic acid delivery |
US8980860B2 (en) | 2010-07-14 | 2015-03-17 | Curna, Inc. | Treatment of discs large homolog (DLG) related diseases by inhibition of natural antisense transcript to DLG |
WO2012016188A2 (en) | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
WO2012016184A2 (en) | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
WO2012044992A2 (en) | 2010-09-30 | 2012-04-05 | Agency For Science, Technology And Research (A*Star) | Methods and reagents for detection and treatment of esophageal metaplasia |
US8481680B2 (en) | 2010-10-05 | 2013-07-09 | Genentech, Inc. | Mutant smoothened and methods of using the same |
US8993533B2 (en) | 2010-10-06 | 2015-03-31 | Curna, Inc. | Treatment of sialidase 4 (NEU4) related diseases by inhibition of natural antisense transcript to NEU4 |
US20140031250A1 (en) | 2010-10-07 | 2014-01-30 | David Tsai Ting | Biomarkers of Cancer |
CA2815212A1 (en) | 2010-10-22 | 2012-04-26 | Curna, Inc. | Treatment of alpha-l-iduronidase (idua) related diseases by inhibition of natural antisense transcript to idua |
CN103201387B (en) | 2010-10-27 | 2018-02-02 | 库尔纳公司 | IFRD1 relevant diseases are treated by suppressing the natural antisense transcript of interferon correlative development regulatory factor 1 (IFRD1) |
CN110123830A (en) | 2010-11-09 | 2019-08-16 | 阿尔尼拉姆医药品有限公司 | Composition and method for inhibiting the lipid of the expression of Eg5 and VEGF gene to prepare |
EP3260540A1 (en) | 2010-11-12 | 2017-12-27 | The General Hospital Corporation | Polycomb-associated non-coding rnas |
WO2012071238A2 (en) | 2010-11-23 | 2012-05-31 | Opko Curna Llc | Treatment of nanog related diseases by inhibition of natural antisense transcript to nanog |
WO2012079046A2 (en) | 2010-12-10 | 2012-06-14 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of klf-1 and bcl11a genes |
WO2012078967A2 (en) | 2010-12-10 | 2012-06-14 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for increasing erythropoietin (epo) production |
DK3202760T3 (en) | 2011-01-11 | 2019-11-25 | Alnylam Pharmaceuticals Inc | PEGYLED LIPIDS AND THEIR USE FOR PHARMACEUTICAL SUPPLY |
WO2012097261A2 (en) | 2011-01-14 | 2012-07-19 | The General Hospital Corporation | Methods targeting mir-128 for regulating cholesterol/lipid metabolism |
SI2670411T1 (en) | 2011-02-02 | 2019-06-28 | Excaliard Pharmaceuticals, Inc. | Antisense compounds targeting connective tissue growth factor (ctgf) for use in a method of treating keloids or hypertrophic scars |
US20140044644A1 (en) | 2011-02-21 | 2014-02-13 | University Of Zurich | Ankyrin g and modulators thereof for the treatment of neurodegenerative disorders |
US9562853B2 (en) | 2011-02-22 | 2017-02-07 | Vanderbilt University | Nonaqueous backscattering interferometric methods |
SG193923A1 (en) | 2011-03-29 | 2013-11-29 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expression of tmprss6 gene |
RU2620980C2 (en) | 2011-06-09 | 2017-05-30 | Курна, Инк. | Treatment of diseases associated with frataxin (fxn), by inhibiting natural antisense fxn transcript |
CN112111492A (en) | 2011-06-21 | 2020-12-22 | 阿尔尼拉姆医药品有限公司 | Compositions and methods for inhibiting expression of apolipoprotein C-III (APOC3) gene |
KR102395085B1 (en) | 2011-06-21 | 2022-05-09 | 알닐람 파마슈티칼스 인코포레이티드 | Angiopoietin-like 3(angptl3) irna compostions and methods of use thereof |
WO2012177949A2 (en) | 2011-06-21 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibition of expression of protein c (proc) genes |
WO2012178033A2 (en) | 2011-06-23 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Serpina1 sirnas: compositions of matter and methods of treatment |
BR112014000443B1 (en) | 2011-07-08 | 2021-03-23 | Epigenomics Ag | METHODS FOR DETERMINING THE PROGNOSIS OF AN INDIVIDUAL WITH CANCER |
EP2739735A2 (en) | 2011-08-01 | 2014-06-11 | Alnylam Pharmaceuticals, Inc. | Method for improving the success rate of hematopoietic stem cell transplants |
EP2756080B1 (en) | 2011-09-14 | 2019-02-20 | Translate Bio MA, Inc. | Multimeric oligonucleotide compounds |
EP2755692B1 (en) | 2011-09-14 | 2020-11-25 | Northwestern University | Nanoconjugates able to cross the blood-brain barrier |
CA2849476A1 (en) | 2011-09-27 | 2013-04-04 | Alnylam Pharmaceuticals, Inc. | Di-aliphatic substituted pegylated lipids |
EP2766482B1 (en) | 2011-10-11 | 2016-12-07 | The Brigham and Women's Hospital, Inc. | Micrornas in neurodegenerative disorders |
EP2790736B1 (en) | 2011-12-12 | 2018-01-31 | Oncoimmunin, Inc. | In vivo delivery of oligonucleotides |
EP4144378A1 (en) | 2011-12-16 | 2023-03-08 | ModernaTX, Inc. | Modified nucleoside, nucleotide, and nucleic acid compositions |
JP2015511494A (en) | 2012-03-15 | 2015-04-20 | キュアナ,インク. | Treatment of BDNF-related diseases by inhibition of natural antisense transcripts against brain-derived neurotrophic factor (BDNF) |
CA2868391A1 (en) | 2012-04-02 | 2013-10-10 | Stephane Bancel | Polynucleotides comprising n1-methyl-pseudouridine and methods for preparing the same |
JP2015513914A (en) | 2012-04-02 | 2015-05-18 | モデルナ セラピューティクス インコーポレイテッドModerna Therapeutics,Inc. | Modified polynucleotides for the production of secreted proteins |
US9133461B2 (en) | 2012-04-10 | 2015-09-15 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the ALAS1 gene |
JP2015518485A (en) | 2012-04-20 | 2015-07-02 | アプタミアール セラピューティクス インコーポレイテッド | Thermogenic miRNA regulator |
US9127274B2 (en) | 2012-04-26 | 2015-09-08 | Alnylam Pharmaceuticals, Inc. | Serpinc1 iRNA compositions and methods of use thereof |
EP2841572B1 (en) | 2012-04-27 | 2019-06-19 | Duke University | Genetic correction of mutated genes |
US9273949B2 (en) | 2012-05-11 | 2016-03-01 | Vanderbilt University | Backscattering interferometric methods |
EA201492123A1 (en) | 2012-05-16 | 2015-10-30 | Рана Терапьютикс, Инк. | COMPOSITIONS AND METHODS FOR MODULATING THE EXPRESSION OF THE SMN GENES FAMILY |
AU2013262663A1 (en) | 2012-05-16 | 2015-01-22 | The General Hospital Corporation D/B/A Massachusetts General Hospital | Compositions and methods for modulating gene expression |
WO2014022852A1 (en) | 2012-08-03 | 2014-02-06 | Aptamir Therapeutics, Inc. | Cell-specific delivery of mirna modulators for the treatment of obesity and related disorders |
JP5685232B2 (en) * | 2012-09-07 | 2015-03-18 | ファーマサイクリクス,インコーポレイテッド | High purity texaphyrin metal complex |
SI2922554T1 (en) | 2012-11-26 | 2022-06-30 | Modernatx, Inc. | Terminally modified rna |
EP3434774A1 (en) | 2013-01-17 | 2019-01-30 | ModernaTX, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
AU2014216112B2 (en) | 2013-02-15 | 2019-02-21 | Allergan, Inc. | Sustained drug delivery implant |
WO2014130922A1 (en) | 2013-02-25 | 2014-08-28 | Trustees Of Boston University | Compositions and methods for treating fungal infections |
WO2014159813A1 (en) | 2013-03-13 | 2014-10-02 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
KR102605775B1 (en) | 2013-03-14 | 2023-11-29 | 알닐람 파마슈티칼스 인코포레이티드 | Complement component c5 irna compositions and methods of use thereof |
EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
EP2978446B1 (en) | 2013-03-27 | 2020-03-04 | The General Hospital Corporation | Anti-cd33 antibody for use in treating alzheimer's disease |
WO2014172698A1 (en) | 2013-04-19 | 2014-10-23 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulation nucleic acids through nonsense mediated decay |
JP6276390B2 (en) * | 2013-05-21 | 2018-02-07 | 成都先導薬物開発有限公司 | Method of cell membrane permeation of compounds |
EP3029059B1 (en) * | 2013-05-21 | 2018-07-04 | Hitgen Ltd. | Compound administration precursor and medicament carrier preparation |
RS57418B1 (en) | 2013-05-22 | 2018-09-28 | Alnylam Pharmaceuticals Inc | Serpina1 irna compositions and methods of use thereof |
AU2014280847B2 (en) | 2013-06-13 | 2019-07-04 | Antisense Therapeutics Ltd | Combination therapy |
JP7019233B2 (en) | 2013-07-11 | 2022-02-15 | モデルナティエックス インコーポレイテッド | Compositions and Methods of Use Containing Synthetic polynucleotides and Synthetic sgRNAs Encoding CRISPR-Related Proteins |
US10894963B2 (en) | 2013-07-25 | 2021-01-19 | Exicure, Inc. | Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use |
ES2773547T3 (en) | 2013-08-08 | 2020-07-13 | Scripps Research Inst | An in vitro nucleic acid site specific enzymatic labeling procedure by incorporating unnatural nucleotides |
US20160194625A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
US20160194368A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Circular polynucleotides |
CN105793423A (en) | 2013-10-02 | 2016-07-20 | 阿尔尼拉姆医药品有限公司 | Compositions and methods for inhibiting expression of the LECT2 gene |
EP3052521A1 (en) | 2013-10-03 | 2016-08-10 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor |
JP6613227B2 (en) | 2013-10-04 | 2019-11-27 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | Composition and method for inhibiting the expression of ALAS1 gene |
JP6621409B2 (en) | 2013-11-22 | 2019-12-18 | ミナ セラピューティクス リミテッド | C / EBPα small molecule activated RNA composition |
CA2844640A1 (en) | 2013-12-06 | 2015-06-06 | The University Of British Columbia | Method for treatment of castration-resistant prostate cancer |
IL282401B (en) | 2013-12-12 | 2022-08-01 | Alnylam Pharmaceuticals Inc | Complement component irna compositions and methods of use thereof |
EP3102197B1 (en) | 2014-02-04 | 2018-08-29 | Genentech, Inc. | Mutant smoothened and methods of using the same |
WO2015123264A1 (en) | 2014-02-11 | 2015-08-20 | Alnylam Pharmaceuticals, Inc. | Ketohexokinase (khk) irna compositions and methods of use thereof |
EP3943607A1 (en) | 2014-04-09 | 2022-01-26 | The Scripps Research Institute | Import of unnatural or modified nucleoside triphosphates into cells via nucleic acid triphosphate transporters |
EP4162940A1 (en) | 2014-04-17 | 2023-04-12 | Biogen MA Inc. | Compositions and methods for modulation of smn2 splicing in a subject |
WO2015171918A2 (en) | 2014-05-07 | 2015-11-12 | Louisiana State University And Agricultural And Mechanical College | Compositions and uses for treatment thereof |
WO2015175510A1 (en) | 2014-05-12 | 2015-11-19 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating a serpinc1-associated disorder |
EA201692370A1 (en) | 2014-05-22 | 2017-03-31 | Элнилэм Фармасьютикалз, Инк. | COMPOSITIONS of mRNA ANGIOTENZINOGENA (AGT) AND METHODS OF THEIR USE |
CN106661580B (en) | 2014-06-10 | 2022-02-15 | 鹿特丹伊拉斯谟大学医疗中心 | Antisense oligonucleotides for treating pompe disease |
WO2015191797A1 (en) | 2014-06-11 | 2015-12-17 | Board Of Regents, The University Of Texas System | Texaphyrin-pt(iv) conjugates and compositions for use in overcoming platinum resistance |
EP3161159B1 (en) | 2014-06-25 | 2020-08-05 | The General Hospital Corporation | Targeting human satellite ii (hsatii) |
CA2955250A1 (en) | 2014-07-16 | 2016-01-21 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
WO2016014846A1 (en) | 2014-07-23 | 2016-01-28 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of intrabodies |
MX2017001432A (en) | 2014-07-31 | 2017-05-09 | Uab Res Found | Apoe mimetic peptides and higher potency to clear plasma cholesterol. |
WO2016033424A1 (en) | 2014-08-29 | 2016-03-03 | Genzyme Corporation | Methods for the prevention and treatment of major adverse cardiovascular events using compounds that modulate apolipoprotein b |
CN107106704A (en) | 2014-08-29 | 2017-08-29 | 儿童医疗中心有限公司 | Method and composition for treating cancer |
EP3191591A1 (en) | 2014-09-12 | 2017-07-19 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting complement component c5 and methods of use thereof |
EP3198012B1 (en) | 2014-09-26 | 2019-09-04 | University of Massachusetts | Rna-modulating agents |
EP3207138B1 (en) | 2014-10-17 | 2020-07-15 | Alnylam Pharmaceuticals, Inc. | Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof |
EP3212794B1 (en) | 2014-10-30 | 2021-04-07 | Genzyme Corporation | Polynucleotide agents targeting serpinc1 (at3) and methods of use thereof |
JOP20200092A1 (en) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | HEPATITIS B VIRUS (HBV) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
CN107250362B (en) | 2014-11-17 | 2021-10-22 | 阿尔尼拉姆医药品有限公司 | Apolipoprotein C3(APOC3) iRNA compositions and methods of use thereof |
CN107106493A (en) | 2014-11-21 | 2017-08-29 | 西北大学 | The sequence-specific cellular uptake of spherical nucleic acid nano particle conjugate |
EP3229842B1 (en) | 2014-12-08 | 2022-07-06 | The Board of Regents of The University of Texas System | Lipocationic polymers and uses thereof |
JP2018504380A (en) | 2014-12-18 | 2018-02-15 | アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. | REVERSIR ™ compounds |
JP2018506715A (en) | 2015-01-23 | 2018-03-08 | ヴァンダービルト ユニバーシティー | Robust interferometer and method of use |
EP3256487A4 (en) | 2015-02-09 | 2018-07-18 | Duke University | Compositions and methods for epigenome editing |
CA2976445A1 (en) | 2015-02-13 | 2016-08-18 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
EP3262173A2 (en) | 2015-02-23 | 2018-01-03 | Crispr Therapeutics AG | Materials and methods for treatment of human genetic diseases including hemoglobinopathies |
WO2016164463A1 (en) | 2015-04-07 | 2016-10-13 | The General Hospital Corporation | Methods for reactivating genes on the inactive x chromosome |
WO2016164746A1 (en) | 2015-04-08 | 2016-10-13 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the lect2 gene |
US10656025B2 (en) | 2015-06-10 | 2020-05-19 | Ekos Corporation | Ultrasound catheter |
EP3307316A1 (en) | 2015-06-12 | 2018-04-18 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions and methods of use thereof |
WO2016205323A1 (en) | 2015-06-18 | 2016-12-22 | Alnylam Pharmaceuticals, Inc. | Polynucleotde agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof |
WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
CN108139375A (en) | 2015-06-26 | 2018-06-08 | 贝斯以色列女执事医疗中心股份有限公司 | Target the cancer therapy for inhibiting the four transmembrane proteins 33 (TSPAN33) in cell derived from marrow sample |
EP3314027A4 (en) | 2015-06-29 | 2019-07-03 | Caris Science, Inc. | Therapeutic oligonucleotides |
US10494632B2 (en) | 2015-07-10 | 2019-12-03 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (IGFALS) compositions and methods of use thereof |
EP3919619A1 (en) | 2015-07-17 | 2021-12-08 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
CA2993652A1 (en) | 2015-07-28 | 2017-02-02 | Caris Science, Inc. | Targeted oligonucleotides |
CN114525280A (en) | 2015-09-02 | 2022-05-24 | 阿尔尼拉姆医药品有限公司 | iRNA compositions of programmed cell death 1 ligand 1(PD-L1) and methods of use thereof |
CN108271360B (en) | 2015-09-14 | 2023-01-24 | 得克萨斯州大学系统董事会 | Lipophilic cationic dendritic polymer and use thereof |
AU2016339053A1 (en) | 2015-09-24 | 2018-04-12 | Crispr Therapeutics Ag | Novel family of RNA-programmable endonucleases and their uses in genome editing and other applications |
EP4089175A1 (en) | 2015-10-13 | 2022-11-16 | Duke University | Genome engineering with type i crispr systems in eukaryotic cells |
EP3368063B1 (en) | 2015-10-28 | 2023-09-06 | Vertex Pharmaceuticals Inc. | Materials and methods for treatment of duchenne muscular dystrophy |
WO2017075670A1 (en) | 2015-11-05 | 2017-05-11 | Children's Hospital Los Angeles | "mobilizing leukemia cells" |
BR112018008971A2 (en) | 2015-11-06 | 2018-11-27 | Crispr Therapeutics Ag | Materials and Methods for Treatment of Type 1a Glycogen Storage Disease |
AU2016355178B9 (en) | 2015-11-19 | 2019-05-30 | Massachusetts Institute Of Technology | Lymphocyte antigen CD5-like (CD5L)-interleukin 12B (p40) heterodimers in immunity |
EP3967758A1 (en) | 2015-12-01 | 2022-03-16 | CRISPR Therapeutics AG | Materials and methods for treatment of alpha-1 antitrypsin deficiency |
AU2015416656B2 (en) | 2015-12-07 | 2023-02-23 | Erasmus University Medical Center Rotterdam | Enzymatic replacement therapy and antisense therapy for Pompe disease |
US11761007B2 (en) | 2015-12-18 | 2023-09-19 | The Scripps Research Institute | Production of unnatural nucleotides using a CRISPR/Cas9 system |
AU2016376191A1 (en) | 2015-12-23 | 2018-07-12 | Crispr Therapeutics Ag | Materials and methods for treatment of amyotrophic lateral sclerosis and/or frontal temporal lobular degeneration |
WO2017132483A1 (en) | 2016-01-29 | 2017-08-03 | Vanderbilt University | Free-solution response function interferometry |
WO2017134529A1 (en) | 2016-02-02 | 2017-08-10 | Crispr Therapeutics Ag | Materials and methods for treatment of severe combined immunodeficiency (scid) or omenn syndrome |
AU2017213826A1 (en) | 2016-02-04 | 2018-08-23 | Curis, Inc. | Mutant smoothened and methods of using the same |
US20190112353A1 (en) | 2016-02-18 | 2019-04-18 | Crispr Therapeutics Ag | Materials and methods for treatment of severe combined immunodeficiency (scid) or omenn syndrome |
JP7033072B2 (en) | 2016-02-25 | 2022-03-09 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッド | Treatment for fibrosis targeting SMOC2 |
WO2017158422A1 (en) | 2016-03-16 | 2017-09-21 | Crispr Therapeutics Ag | Materials and methods for treatment of hereditary haemochromatosis |
JP2019516393A (en) | 2016-03-18 | 2019-06-20 | カリス サイエンス インコーポレイテッド | Oligonucleotide probes and uses thereof |
AU2017252023A1 (en) | 2016-04-18 | 2018-11-15 | Crispr Therapeutics Ag | Materials and methods for treatment of hemoglobinopathies |
US10335608B2 (en) | 2016-04-20 | 2019-07-02 | Theralase Technologies, Inc. | Photodynamic compounds and methods for activating them using ionizing radiation and/or other electromagnetic radiation for therapy and/or diagnostics |
WO2017191503A1 (en) | 2016-05-05 | 2017-11-09 | Crispr Therapeutics Ag | Materials and methods for treatment of hemoglobinopathies |
CN109414408B (en) | 2016-05-16 | 2022-03-29 | 得克萨斯州大学系统董事会 | Cationic sulfonamide amino lipids and amphiphilic zwitterionic amino lipids |
WO2017205686A1 (en) | 2016-05-25 | 2017-11-30 | Caris Science, Inc. | Oligonucleotide probes and uses thereof |
US20190256845A1 (en) | 2016-06-10 | 2019-08-22 | Alnylam Pharmaceuticals, Inc. | COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) |
WO2017223528A1 (en) | 2016-06-24 | 2017-12-28 | The Scripps Research Institute | Novel nucleoside triphosphate transporter and uses thereof |
WO2018002812A1 (en) | 2016-06-29 | 2018-01-04 | Crispr Therapeutics Ag | Materials and methods for treatment of myotonic dystrophy type 1 (dm1) and other related disorders |
WO2018002762A1 (en) | 2016-06-29 | 2018-01-04 | Crispr Therapeutics Ag | Materials and methods for treatment of amyotrophic lateral sclerosis (als) and other related disorders |
WO2018002783A1 (en) | 2016-06-29 | 2018-01-04 | Crispr Therapeutics Ag | Materials and methods for treatment of friedreich ataxia and other related disorders |
AU2017292173B2 (en) | 2016-07-06 | 2022-01-13 | Vertex Pharmaceuticals Incorporated | Materials and methods for treatment of pain related disorders |
EP3481856A1 (en) | 2016-07-06 | 2019-05-15 | Crispr Therapeutics AG | Materials and methods for treatment of pain related disorders |
WO2018007871A1 (en) | 2016-07-08 | 2018-01-11 | Crispr Therapeutics Ag | Materials and methods for treatment of transthyretin amyloidosis |
US11253601B2 (en) | 2016-07-11 | 2022-02-22 | Translate Bio Ma, Inc. | Nucleic acid conjugates and uses thereof |
WO2018020323A2 (en) | 2016-07-25 | 2018-02-01 | Crispr Therapeutics Ag | Materials and methods for treatment of fatty acid disorders |
NL2017295B1 (en) | 2016-08-05 | 2018-02-14 | Univ Erasmus Med Ct Rotterdam | Antisense oligomeric compound for Pompe disease |
NL2017294B1 (en) | 2016-08-05 | 2018-02-14 | Univ Erasmus Med Ct Rotterdam | Natural cryptic exon removal by pairs of antisense oligonucleotides. |
CA3037046A1 (en) | 2016-10-31 | 2018-05-03 | University Of Massachusetts | Targeting microrna-101-3p in cancer therapy |
TWI788312B (en) | 2016-11-23 | 2023-01-01 | 美商阿尼拉製藥公司 | SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
EP3555296A4 (en) | 2016-12-13 | 2020-07-29 | Seattle Children's Hospital (DBA Seattle Children's Research Institute) | Methods of exogenous drug activation of chemical-induced signaling complexes expressed in engineered cells in vitro and in vivo |
KR20230166146A (en) | 2016-12-16 | 2023-12-06 | 알닐람 파마슈티칼스 인코포레이티드 | Methods for treating or preventing ttr-associated diseases using transthyretin(ttr) irna compositions |
IL301053A (en) | 2017-01-23 | 2023-05-01 | Regeneron Pharma | Hsd17b13 variants and uses thereof |
US11407997B2 (en) | 2017-02-22 | 2022-08-09 | Crispr Therapeutics Ag | Materials and methods for treatment of primary hyperoxaluria type 1 (PH1) and other alanine-glyoxylate aminotransferase (AGXT) gene related conditions or disorders |
WO2018154439A1 (en) | 2017-02-22 | 2018-08-30 | Crispr Therapeutics Ag | Materials and methods for treatment of spinocerebellar ataxia type 1 (sca1) and other spinocerebellar ataxia type 1 protein (atxn1) gene related conditions or disorders |
EP3585807A1 (en) | 2017-02-22 | 2020-01-01 | CRISPR Therapeutics AG | Materials and methods for treatment of early onset parkinson's disease (park1) and other synuclein, alpha (snca) gene related conditions or disorders |
CA3054031A1 (en) | 2017-02-22 | 2018-08-30 | Crispr Therapeutics Ag | Compositions and methods for gene editing |
EP3585900B1 (en) | 2017-02-22 | 2022-12-21 | CRISPR Therapeutics AG | Materials and methods for treatment of spinocerebellar ataxia type 2 (sca2) and other spinocerebellar ataxia type 2 protein (atxn2) gene related conditions or disorders |
AU2018254437A1 (en) | 2017-04-18 | 2019-11-28 | Alnylam Pharmaceuticals, Inc. | Methods for the treatment of subjects having a hepatitis B virus (HBV) infection |
EP3612232A1 (en) | 2017-04-21 | 2020-02-26 | The Broad Institute, Inc. | Targeted delivery to beta cells |
WO2018209270A1 (en) | 2017-05-11 | 2018-11-15 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (snas) |
US11622977B2 (en) | 2017-05-12 | 2023-04-11 | Crispr Therapeutics Ag | Materials and methods for engineering cells and uses thereof in immuno-oncology |
CN111051512A (en) | 2017-07-11 | 2020-04-21 | 辛索克斯公司 | Incorporation of non-natural nucleotides and methods thereof |
WO2019014530A1 (en) | 2017-07-13 | 2019-01-17 | Alnylam Pharmaceuticals Inc. | Lactate dehydrogenase a (ldha) irna compositions and methods of use thereof |
WO2019028425A1 (en) | 2017-08-03 | 2019-02-07 | Synthorx, Inc. | Cytokine conjugates for the treatment of autoimmune diseases |
WO2019048632A1 (en) | 2017-09-08 | 2019-03-14 | Mina Therapeutics Limited | Stabilized hnf4a sarna compositions and methods of use |
EP4219715A3 (en) | 2017-09-08 | 2023-09-06 | MiNA Therapeutics Limited | Stabilized cebpa sarna compositions and methods of use |
SG11202003464VA (en) | 2017-10-17 | 2020-05-28 | Crispr Therapeutics Ag | Compositions and methods for gene editing for hemophilia a |
US20210180091A1 (en) | 2017-10-26 | 2021-06-17 | Vertex Pharmaceuticals Incorporated | Materials and methods for treatment of hemoglobinopathies |
WO2019089922A1 (en) | 2017-11-01 | 2019-05-09 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof |
US20210032622A1 (en) | 2017-11-09 | 2021-02-04 | Crispr Therapeutics Ag | Self-inactivating (sin) crispr/cas or crispr/cpf1 systems and uses thereof |
EP3714054A1 (en) | 2017-11-20 | 2020-09-30 | Alnylam Pharmaceuticals, Inc. | Serum amyloid p component (apcs) irna compositions and methods of use thereof |
CN111727251A (en) | 2017-11-21 | 2020-09-29 | 克里斯珀医疗股份公司 | Materials and methods for treating autosomal dominant retinitis pigmentosa |
US20200384033A1 (en) | 2017-12-05 | 2020-12-10 | Vertex Pharmaceuticals Incorporated | Crispr-cas9 modified cd34+ human hematopoietic stem and progenitor cells and uses thereof |
CA3084825A1 (en) | 2017-12-14 | 2019-06-20 | Crispr Therapeutics Ag | Novel rna-programmable endonuclease systems and their use in genome editing and other applications |
AU2018388484A1 (en) | 2017-12-18 | 2020-07-30 | Alnylam Pharmaceuticals, Inc. | High mobility group box-1 (HMGB1) iRNA compositions and methods of use thereof |
EP3728595A1 (en) | 2017-12-21 | 2020-10-28 | CRISPR Therapeutics AG | Materials and methods for treatment of usher syndrome type 2a and/or non-syndromic autosomal recessive retinitis pigmentosa (arrp) |
AU2018393050A1 (en) | 2017-12-21 | 2020-06-18 | Bayer Healthcare Llc | Materials and methods for treatment of Usher Syndrome Type 2A |
CA3088180A1 (en) | 2018-01-12 | 2019-07-18 | Crispr Therapeutics Ag | Compositions and methods for gene editing by targeting transferrin |
US20190233816A1 (en) | 2018-01-26 | 2019-08-01 | Massachusetts Institute Of Technology | Structure-guided chemical modification of guide rna and its applications |
MA51787A (en) | 2018-02-05 | 2020-12-16 | Vertex Pharma | SUBSTANCES AND METHODS OF TREATMENT OF HEMOGLOBINOPATHIES |
MA51788A (en) | 2018-02-05 | 2020-12-16 | Vertex Pharma | SUBSTANCES AND METHODS FOR TREATING HEMOGLOBINOPATHIES |
US20210130824A1 (en) | 2018-02-16 | 2021-05-06 | Crispr Therapeutics Ag | Compositions and methods for gene editing by targeting fibrinogen-alpha |
KR20200127207A (en) | 2018-02-26 | 2020-11-10 | 신톡스, 인크. | IL-15 conjugate and uses thereof |
US10611986B1 (en) | 2018-03-15 | 2020-04-07 | Earthcare Labs, Llc | Cleaning composition comprising a cationic/nonionic mixture |
EP3768834A1 (en) | 2018-03-19 | 2021-01-27 | CRISPR Therapeutics AG | Novel rna-programmable endonuclease systems and uses thereof |
EP4051799A2 (en) | 2018-03-30 | 2022-09-07 | Rheinische Friedrich-Wilhelms-Universität Bonn | Aptamers for targeted activaton of t cell-mediated immunity |
CN116536272A (en) | 2018-04-06 | 2023-08-04 | 儿童医疗中心有限公司 | Compositions and methods for somatic reprogramming and imprinting |
EP4242307A3 (en) | 2018-04-12 | 2023-12-27 | MiNA Therapeutics Limited | Sirt1-sarna compositions and methods of use |
WO2019204668A1 (en) | 2018-04-18 | 2019-10-24 | Casebia Therapeutics Limited Liability Partnership | Compositions and methods for knockdown of apo(a) by gene editing for treatment of cardiovascular disease |
BR112020022546A8 (en) | 2018-05-07 | 2022-05-17 | Alnylam Pharmaceuticals Inc | extra-hepatic delivery |
TW202016304A (en) | 2018-05-14 | 2020-05-01 | 美商阿尼拉製藥公司 | Angiotensinogen (agt) irna compositions and methods of use thereof |
BR112021001613A2 (en) | 2018-08-13 | 2021-05-04 | Alnylam Pharmaceuticals, Inc. | double-stranded ribonucleic acid agents, cell, pharmaceutical compositions, methods of inhibiting gene expression, inhibiting replication and treating a subject, methods for reducing the level of an antigen and for reducing viral load, and use of an agent dsrna |
US20210348162A1 (en) | 2018-08-16 | 2021-11-11 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the lect2 gene |
US20210292766A1 (en) | 2018-08-29 | 2021-09-23 | University Of Massachusetts | Inhibition of Protein Kinases to Treat Friedreich Ataxia |
US20210332367A1 (en) | 2018-09-18 | 2021-10-28 | Alnylam Pharmaceuticals, Inc. | KETOHEXOKINASE (KHK) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
TW202028465A (en) | 2018-09-28 | 2020-08-01 | 美商阿尼拉製藥公司 | Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases |
US20210348159A1 (en) | 2018-10-17 | 2021-11-11 | Crispr Therapeutics Ag | Compositions and methods for delivering transgenes |
US10913951B2 (en) | 2018-10-31 | 2021-02-09 | University of Pittsburgh—of the Commonwealth System of Higher Education | Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure |
WO2020132521A1 (en) | 2018-12-20 | 2020-06-25 | Praxis Precision Medicines, Inc. | Compositions and methods for the treatment of kcnt1 related disorders |
EP4285929A3 (en) | 2018-12-20 | 2024-03-06 | Humabs Biomed SA | Combination hbv therapy |
SG11202107669WA (en) | 2019-01-16 | 2021-08-30 | Genzyme Corp | Serpinc1 irna compositions and methods of use thereof |
AU2020218203A1 (en) | 2019-02-06 | 2021-08-26 | Synthorx, Inc. | IL-2 conjugates and methods of use thereof |
MA54951A (en) | 2019-02-15 | 2021-12-22 | Bayer Healthcare Llc | GENE EDITING FOR HEMOPHILIA A WITH ENHANCED FACTOR VIII EXPRESSION |
WO2020171889A1 (en) | 2019-02-19 | 2020-08-27 | University Of Rochester | Blocking lipid accumulation or inflammation in thyroid eye disease |
SG11202109741VA (en) | 2019-03-12 | 2021-10-28 | Crispr Therapeutics Ag | Novel high fidelity rna-programmable endonuclease systems and uses thereof |
US20220211740A1 (en) | 2019-04-12 | 2022-07-07 | Mina Therapeutics Limited | Sirt1-sarna compositions and methods of use |
BR112021022806A2 (en) | 2019-05-13 | 2022-01-25 | Vir Biotechnology Inc | Method for treating chronic hbv infection, sirna, uses of a sirna, and of a sirna and peg-ifna and of a sirna, peg-ifna and an nrti, method, composition for use or use and kit |
JP2022532652A (en) | 2019-05-17 | 2022-07-15 | アルニラム ファーマスーティカルズ インコーポレイテッド | Oral delivery of oligonucleotides |
US11879145B2 (en) | 2019-06-14 | 2024-01-23 | The Scripps Research Institute | Reagents and methods for replication, transcription, and translation in semi-synthetic organisms |
WO2021022108A2 (en) | 2019-08-01 | 2021-02-04 | Alnylam Pharmaceuticals, Inc. | CARBOXYPEPTIDASE B2 (CPB2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
WO2021022109A1 (en) | 2019-08-01 | 2021-02-04 | Alnylam Pharmaceuticals, Inc. | SERPIN FAMILY F MEMBER 2 (SERPINF2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
WO2021030522A1 (en) | 2019-08-13 | 2021-02-18 | Alnylam Pharmaceuticals, Inc. | SMALL RIBOSOMAL PROTEIN SUBUNIT 25 (RPS25) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF |
CN114555128A (en) | 2019-08-15 | 2022-05-27 | 新索思股份有限公司 | Combination immunooncology therapy with IL-2 conjugates |
JP2022545101A (en) | 2019-08-19 | 2022-10-25 | ミナ セラピューティクス リミテッド | Oligonucleotide conjugate compositions and methods of use |
KR20220051355A (en) | 2019-08-23 | 2022-04-26 | 신톡스, 인크. | IL-15 conjugates and uses thereof |
EP4025694A1 (en) | 2019-09-03 | 2022-07-13 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the lect2 gene |
WO2021050554A1 (en) | 2019-09-10 | 2021-03-18 | Synthorx, Inc. | Il-2 conjugates and methods of use to treat autoimmune diseases |
US20220389429A1 (en) | 2019-10-04 | 2022-12-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing ugt1a1 gene expression |
WO2021076828A1 (en) | 2019-10-18 | 2021-04-22 | Alnylam Pharmaceuticals, Inc. | Solute carrier family member irna compositions and methods of use thereof |
AU2020369515A1 (en) | 2019-10-22 | 2022-04-21 | Alnylam Pharmaceuticals, Inc. | Complement component C3 iRNA compositions and methods of use thereof |
TW202132567A (en) | 2019-11-01 | 2021-09-01 | 美商阿尼拉製藥公司 | Huntingtin (htt) irna agent compositions and methods of use thereof |
EP4051796A1 (en) | 2019-11-01 | 2022-09-07 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing dnajb1-prkaca fusion gene expression |
JP2022554272A (en) | 2019-11-04 | 2022-12-28 | シンソークス, インコーポレイテッド | Interleukin 10 conjugates and uses thereof |
KR20220110749A (en) | 2019-11-06 | 2022-08-09 | 알닐람 파마슈티칼스 인코포레이티드 | extrahepatic transmission |
WO2021092145A1 (en) | 2019-11-06 | 2021-05-14 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna composition and methods of use thereof for treating or preventing ttr-associated ocular diseases |
WO2021096763A1 (en) | 2019-11-13 | 2021-05-20 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for treating an angiotensinogen- (agt-) associated disorder |
US20230056569A1 (en) | 2019-11-22 | 2023-02-23 | Alnylam Pharmaceuticals, Inc. | Ataxin3 (atxn3) rnai agent compositions and methods of use thereof |
MX2022006433A (en) | 2019-12-13 | 2022-06-23 | Alnylam Pharmaceuticals Inc | Human chromosome 9 open reading frame 72 (c9orf72) irna agent compositions and methods of use thereof. |
WO2021126734A1 (en) | 2019-12-16 | 2021-06-24 | Alnylam Pharmaceuticals, Inc. | Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof |
EP4077674A1 (en) | 2019-12-18 | 2022-10-26 | Alia Therapeutics S.R.L. | Compositions and methods for treating retinitis pigmentosa |
WO2021154941A1 (en) | 2020-01-31 | 2021-08-05 | Alnylam Pharmaceuticals, Inc. | Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als) |
CN115427571A (en) | 2020-02-10 | 2022-12-02 | 阿尔尼拉姆医药品有限公司 | Compositions and methods for silencing VEGF-A expression |
MX2022010052A (en) | 2020-02-18 | 2022-09-05 | Alnylam Pharmaceuticals Inc | Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof. |
EP4114947A1 (en) | 2020-03-05 | 2023-01-11 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases |
KR20220152270A (en) | 2020-03-06 | 2022-11-15 | 알닐람 파마슈티칼스 인코포레이티드 | Compositions and methods for inhibiting the expression of transthyretin (TTR) |
CA3174725A1 (en) | 2020-03-06 | 2021-09-10 | Alnylam Pharmaceuticals, Inc. | Ketohexokinase (khk) irna compositions and methods of use thereof |
EP4121534A1 (en) | 2020-03-18 | 2023-01-25 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant |
WO2021195307A1 (en) | 2020-03-26 | 2021-09-30 | Alnylam Pharmaceuticals, Inc. | Coronavirus irna compositions and methods of use thereof |
US20230190785A1 (en) | 2020-03-30 | 2023-06-22 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing dnajc15 gene expression |
US20230295622A1 (en) | 2020-04-06 | 2023-09-21 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for silencing myoc expression |
EP4133077A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof |
CN116134135A (en) | 2020-04-07 | 2023-05-16 | 阿尔尼拉姆医药品有限公司 | Compositions and methods for silencing SCN9A expression |
WO2021206917A1 (en) | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
BR112022021813A2 (en) | 2020-04-27 | 2023-01-17 | Alnylam Pharmaceuticals Inc | APOLIPOPROTEIN AND (APOE) IRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF |
IL297680A (en) | 2020-04-30 | 2022-12-01 | Alnylam Pharmaceuticals Inc | Complement factor b (cfb) irna compositions and methods of use thereof |
EP4150087A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2) |
WO2021231691A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of retinoschisin 1 (rsi) |
EP4150076A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2) |
EP4150090A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of otoferlin (otof) |
EP4150078A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl) |
EP4150088A1 (en) | 2020-05-15 | 2023-03-22 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1) |
WO2021231673A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2) |
WO2021231685A1 (en) | 2020-05-15 | 2021-11-18 | Korro Bio, Inc. | Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1) |
EP4153746A1 (en) | 2020-05-21 | 2023-03-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting marc1 gene expression |
BR112022023465A2 (en) | 2020-05-22 | 2023-01-10 | Wave Life Sciences Ltd | DOUBLE-STRANDED OLIGONUCLEOTIDE (DSRNAI) AGENT, CHIRALLY CONTROLLED OLIGONUCLEOTIDE COMPOSITION, DOUBLE-STRANDED OLIGONUCLEOTIDE, METHOD FOR REDUCING THE LEVEL AND/OR ACTIVITY OF A TRANSCRIPT OR A PROTEIN ENCODED BY THE SAME, AND METHOD FOR ALLELE-SPECIFIC DELETION OF A TRANSCRIPTION OF A NUCLEIC ACID SEQUENCE |
AR122534A1 (en) | 2020-06-03 | 2022-09-21 | Triplet Therapeutics Inc | METHODS FOR THE TREATMENT OF NUCLEOTIDE REPEAT EXPANSION DISORDERS ASSOCIATED WITH MSH3 ACTIVITY |
EP4162050A1 (en) | 2020-06-09 | 2023-04-12 | Alnylam Pharmaceuticals, Inc. | Rnai compositions and methods of use thereof for delivery by inhalation |
BR112022024420A2 (en) | 2020-06-18 | 2023-01-17 | Alnylam Pharmaceuticals Inc | XANTHINE DEHYDROGENASE (XDH) IRNA COMPOSITIONS AND METHODS OF USE THEREOF |
CA3182458A1 (en) | 2020-06-24 | 2021-12-30 | Laura ROSEN | Engineered hepatitis b virus neutralizing antibodies and uses thereof |
AU2021296622A1 (en) | 2020-06-25 | 2023-02-23 | Synthorx, Inc. | Immuno oncology combination therapy with IL-2 conjugates and anti-EGFR antibodies |
WO2022011214A1 (en) | 2020-07-10 | 2022-01-13 | Alnylam Pharmaceuticals, Inc. | Circular sirnas |
JP2023540429A (en) | 2020-07-10 | 2023-09-25 | アンセルム(アンスティチュート・ナシオナル・ドゥ・ラ・サンテ・エ・ドゥ・ラ・ルシェルシュ・メディカル) | Methods and compositions for treating epilepsy |
CA3189244A1 (en) | 2020-08-14 | 2022-02-17 | Jonathan L. Sessler | Texaphyrin derivatives for manganese chemotherapy, photoacoustic imaging, and photothermal therapy |
EP4217489A1 (en) | 2020-09-24 | 2023-08-02 | Alnylam Pharmaceuticals, Inc. | Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof |
US20230392134A1 (en) | 2020-09-30 | 2023-12-07 | Crispr Therapeutics Ag | Materials and methods for treatment of amyotrophic lateral sclerosis |
TW202229552A (en) | 2020-10-05 | 2022-08-01 | 美商艾拉倫製藥股份有限公司 | G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof |
BR112023006024A2 (en) | 2020-10-09 | 2023-05-09 | Synthorx Inc | IMMUNO-ONCOLOGY THERAPIES WITH IL-2 CONJUGATES |
MX2023004029A (en) | 2020-10-09 | 2023-04-27 | Synthorx Inc | Immuno oncology combination therapy with il-2 conjugates and pembrolizumab. |
EP4232582A1 (en) | 2020-10-23 | 2023-08-30 | Alnylam Pharmaceuticals, Inc. | Mucin 5b (muc5b) irna compositions and methods of use thereof |
JP2023549500A (en) | 2020-11-13 | 2023-11-27 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | Coagulation factor V (F5) iRNA composition and method of use thereof |
EP4259795A1 (en) | 2020-12-08 | 2023-10-18 | Alnylam Pharmaceuticals, Inc. | Coagulation factor x (f10) irna compositions and methods of use thereof |
AU2021411579A1 (en) | 2020-12-31 | 2023-07-13 | Alnylam Pharmaceuticals, Inc. | Cyclic-disulfide modified phosphate based oligonucleotide prodrugs |
EP4271695A2 (en) | 2020-12-31 | 2023-11-08 | Alnylam Pharmaceuticals, Inc. | 2'-modified nucleoside based oligonucleotide prodrugs |
WO2022150260A1 (en) | 2021-01-05 | 2022-07-14 | Alnylam Pharmaceuticals, Inc. | COMPLEMENT COMPONENT 9 (C9) iRNA COMPOSITIONS AND METHODS OF USE THEREOF |
TW202305131A (en) | 2021-02-12 | 2023-02-01 | 美商艾拉倫製藥股份有限公司 | SUPEROXIDE DISMUTASE 1 (SOD1) iRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING OR PREVENTING SUPEROXIDE DISMUTASE 1- (SOD1-) ASSOCIATED NEURODEGENERATIVE DISEASES |
WO2022174102A1 (en) | 2021-02-12 | 2022-08-18 | Synthorx, Inc. | Lung cancer combination therapy with il-2 conjugates and an anti-pd-1 antibody or antigen-binding fragment thereof |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990010633A1 (en) * | 1989-03-06 | 1990-09-20 | Board Of Regents, The University Of Texas System | Expanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles |
US5041078A (en) * | 1989-03-06 | 1991-08-20 | Baylor Research Foundation, A Nonprofit Corporation Of The State Of Texas | Photodynamic viral deactivation with sapphyrins |
WO1993014093A1 (en) * | 1992-01-21 | 1993-07-22 | Board Of Regents, The University Of Texas System | Metal complexes of water soluble texaphyrins |
Family Cites Families (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4318825A (en) * | 1979-08-15 | 1982-03-09 | Frame Robert R | Catalytic composite, and method of manufacture |
US4957939A (en) * | 1981-07-24 | 1990-09-18 | Schering Aktiengesellschaft | Sterile pharmaceutical compositions of gadolinium chelates useful enhancing NMR imaging |
US4647447A (en) * | 1981-07-24 | 1987-03-03 | Schering Aktiengesellschaft | Diagnostic media |
US4613322A (en) * | 1982-12-08 | 1986-09-23 | Edelson Richard Leslie | Method and system for externally treating the blood |
FR2540122B1 (en) * | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | NOVEL COMPOUNDS COMPRISING A SEQUENCE OF OLIGONUCLEOTIDE LINKED TO AN INTERCALATION AGENT, THEIR SYNTHESIS PROCESS AND THEIR APPLICATION |
JPS61275228A (en) * | 1985-03-14 | 1986-12-05 | バクスタ−、トラベノ−ル、ラボラトリ−ズ、インコ−ポレイテツド | Photodynamic inactivity of virus in therapeutical protein composition |
US4977177A (en) * | 1985-04-30 | 1990-12-11 | Nippon Petrochemicals Company, Ltd. | Tetrapyrrole polyaminomonocarboxylic acid therapeutic agents |
US4880008A (en) * | 1985-05-08 | 1989-11-14 | The General Hospital Corporation | Vivo enhancement of NMR relaxivity |
US4899755A (en) * | 1985-05-08 | 1990-02-13 | The General Hospital Corporation | Hepatobiliary NMR contrast agents |
CA1315780C (en) * | 1986-01-17 | 1993-04-06 | Yozo Fukuda | Porphyrin derivatives |
US5242797A (en) * | 1986-03-21 | 1993-09-07 | Myron J. Block | Nucleic acid assay method |
US4915683A (en) * | 1986-11-21 | 1990-04-10 | The Medical College Of Wisconsin, Inc. | Antiviral method, agents and apparatus |
US4883790A (en) * | 1987-01-20 | 1989-11-28 | University Of British Columbia | Wavelength-specific cytotoxic agents |
US4878891A (en) * | 1987-06-25 | 1989-11-07 | Baylor Research Foundation | Method for eradicating infectious biological contaminants in body tissues |
JPH0651619B2 (en) * | 1988-05-09 | 1994-07-06 | 株式会社クラレ | Whitening agent |
WO1990001208A1 (en) * | 1988-07-28 | 1990-02-08 | Best Industries, Inc. | Device and method for encapsulating radioactive materials |
US4889755A (en) * | 1988-11-01 | 1989-12-26 | Minnesota Mining And Manufacturing Company | Fragrance releasing pull-out sampler |
US5567687A (en) * | 1989-03-06 | 1996-10-22 | University Of Texas | Texaphyrins and uses thereof |
US5559207A (en) * | 1989-03-06 | 1996-09-24 | Board Of Regents, University Of Texas | Texaphyrin metal complex mediated ester hydrolysis |
US5599923A (en) * | 1989-03-06 | 1997-02-04 | Board Of Regents, University Of Tx | Texaphyrin metal complexes having improved functionalization |
US5256399A (en) * | 1989-03-06 | 1993-10-26 | Board Of Regents, The University Of Texas System | Aromatic pentadentate expanded porphyrins in magnetic resonance imaging |
US5162509A (en) * | 1989-03-06 | 1992-11-10 | Board Of Regents, The University Of Texas System | Process for preparing expanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles |
US5272142A (en) * | 1989-03-06 | 1993-12-21 | Board Of Regents, The University Of Texas System | Expanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles and methods for treating tumors |
US5457183A (en) * | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
US4959363A (en) * | 1989-06-23 | 1990-09-25 | Sterling Drug Inc. | Quinolonecarboxamide compounds, their preparation and use as antivirals. |
FR2650761B1 (en) * | 1989-08-10 | 1994-03-04 | Elf Aquitaine Ste Nale | SUPPORTED METALLOPORPHYRIN OXIDATION CATALYST |
US5219732A (en) * | 1989-09-05 | 1993-06-15 | The Regents Of The University Of California | Antibody-mediated cofactor-driven reactions |
US5457195A (en) * | 1989-12-21 | 1995-10-10 | Board Of Regents, The University Of Texas System | Sapphyrin derivatives and conjugates |
US5159065A (en) * | 1989-12-21 | 1992-10-27 | Board Of Regents, The University Of Texas System | Sapphyrins, derivatives and syntheses |
US5594136A (en) * | 1989-12-21 | 1997-01-14 | Pharmacyclics, Inc. | Texaphyrin solid supports and devices |
EP0533753A1 (en) * | 1990-06-14 | 1993-03-31 | Washington University | Rna hydrolysis/cleavage |
US5252270A (en) * | 1990-12-20 | 1993-10-12 | Basf Aktiengesellschaft | Method of forming foam moldings having varied density regions |
US5272056A (en) * | 1991-01-03 | 1993-12-21 | The Research Foundation Of State University Of New York | Modification of DNA and oligonucleotides using metal complexes of polyaza ligands |
US5595726A (en) * | 1992-01-21 | 1997-01-21 | Pharmacyclics, Inc. | Chromophore probe for detection of nucleic acid |
US5763172A (en) * | 1992-01-21 | 1998-06-09 | Board Of Regents, The University Of Texas System | Method of phosphate ester hydrolysis |
US5607924A (en) * | 1992-01-21 | 1997-03-04 | Pharmacyclics, Inc. | DNA photocleavage using texaphyrins |
US5565552A (en) * | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
US5371199B1 (en) * | 1992-08-14 | 1995-12-26 | Univ Pennsylvania | Substituted porphyrins porphyrin-containing polymers and synthetic methods therefor |
US5798491A (en) * | 1993-06-09 | 1998-08-25 | Board Of Regents, The University Of Texas System | Multi-mechanistic chemical cleavage using certain metal complexes |
KR960010183B1 (en) * | 1993-10-23 | 1996-07-26 | 김광호 | Image recording apparatus and control method thereof for energy economization |
US5633354A (en) * | 1994-09-21 | 1997-05-27 | Pharmacyclics, Inc. | Phosphoramidite derivatives of texaphyrins |
US5756726A (en) * | 1995-06-02 | 1998-05-26 | Pharmacyclics, Inc. | Methods of producing singlet oxygen using compounds having improved functionalization |
US5714328A (en) * | 1995-06-07 | 1998-02-03 | Board Of Regents, The University Of Texas System | RNA photocleavage using texaphyrins |
US5776925A (en) * | 1996-01-25 | 1998-07-07 | Pharmacyclics, Inc. | Methods for cancer chemosensitization |
AU717193B2 (en) * | 1996-03-26 | 2000-03-23 | Pharmacyclics, Inc. | Use of a texaphyrin in photodynamic therapy of pigment-related lesions |
-
1993
- 1993-10-12 US US08/135,118 patent/US5457183A/en not_active Expired - Lifetime
-
1994
- 1994-10-12 JP JP51197695A patent/JP3596816B2/en not_active Expired - Fee Related
- 1994-10-12 WO PCT/US1994/011491 patent/WO1995010307A1/en active IP Right Grant
- 1994-10-12 CA CA002173319A patent/CA2173319C/en not_active Expired - Fee Related
- 1994-10-12 NZ NZ275217A patent/NZ275217A/en not_active IP Right Cessation
- 1994-10-12 ES ES94931812T patent/ES2193163T3/en not_active Expired - Lifetime
- 1994-10-12 EP EP94931812A patent/EP0724457B1/en not_active Expired - Lifetime
- 1994-10-12 SG SG1996009309A patent/SG48392A1/en unknown
- 1994-10-12 PT PT94931812T patent/PT724457E/en unknown
- 1994-10-12 DK DK94931812T patent/DK0724457T3/en active
- 1994-10-12 AT AT94931812T patent/ATE233575T1/en not_active IP Right Cessation
- 1994-10-12 KR KR1019960701880A patent/KR100365058B1/en not_active IP Right Cessation
- 1994-10-12 DE DE69432221T patent/DE69432221T2/en not_active Expired - Lifetime
- 1994-10-12 AU AU80756/94A patent/AU683316B2/en not_active Ceased
-
1995
- 1995-05-10 US US08/437,968 patent/US5622946A/en not_active Expired - Lifetime
- 1995-05-24 US US08/449,681 patent/US5583220A/en not_active Expired - Lifetime
- 1995-06-02 US US08/458,267 patent/US5580543A/en not_active Expired - Lifetime
- 1995-06-02 US US08/458,909 patent/US5587371A/en not_active Expired - Lifetime
- 1995-06-07 US US08/486,967 patent/US5632970A/en not_active Expired - Lifetime
-
1996
- 1996-04-11 NO NO19961436A patent/NO315185B1/en not_active IP Right Cessation
- 1996-09-13 US US08/713,701 patent/US5801229A/en not_active Expired - Lifetime
-
1997
- 1997-11-14 US US08/970,864 patent/US6069140A/en not_active Expired - Lifetime
-
2003
- 2003-11-06 JP JP2003377620A patent/JP2004091495A/en not_active Withdrawn
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990010633A1 (en) * | 1989-03-06 | 1990-09-20 | Board Of Regents, The University Of Texas System | Expanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles |
US5041078A (en) * | 1989-03-06 | 1991-08-20 | Baylor Research Foundation, A Nonprofit Corporation Of The State Of Texas | Photodynamic viral deactivation with sapphyrins |
US5252720A (en) * | 1989-03-06 | 1993-10-12 | Board Of Regents, The University Of Texas System | Metal complexes of water soluble texaphyrins |
WO1993014093A1 (en) * | 1992-01-21 | 1993-07-22 | Board Of Regents, The University Of Texas System | Metal complexes of water soluble texaphyrins |
Non-Patent Citations (16)
Title |
---|
"PORPHYRIN PHOTOSENSITIZATION", 1981, DAVID KESSEL AND THOMAS J. DOUGHERTY, NEW YORK AND LONDON * |
ANTHONY HARRIMAN ET AL.: "METALLOTEXAPHYRINS: A NEW FAMILY OF PHOTOSENSITISERS FOR EFFICIENT GENERATION OF SINGLET OXYGEN.", JOURNAL OF THE CHEMICAL SOCIETY, CHEM. COMMUN., 1989, LETCHWORTH GB, pages 314 - 316 * |
CHEMICAL ABSTRACTS, vol. 117, no. 17, 26 October 1992, Columbus, Ohio, US; abstract no. 166777 * |
CHEMICAL ABSTRACTS, vol. 117, no. 3, 20 July 1992, Columbus, Ohio, US; abstract no. 22546 * |
CHEMICAL ABSTRACTS, vol. 121, no. 19, 7 November 1994, Columbus, Ohio, US; abstract no. 224420 * |
D. MAGDA ET AL.: "SITE-SPECIFIC HYDROLYSIS OF RNA BY EUROPIUM (III) TEXAPHYRIN CONJUGATED TO A SYNTHETIC OLIGODEOXYRIBONUCLEOTIDE.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 116, no. 16, August 1994 (1994-08-01), WASHINGTON, DC US, pages 7439 - 7440, XP000500100, DOI: doi:10.1021/ja00095a070 * |
DATABASE BIOSIS BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; * |
DATABASE MEDLINE US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; * |
EHRENBERG BENJAMIN ET AL.: "SPECTROSCOPY, PHOTOKINETICS AND CELLULAR EFFECT OF FAR-RED AND NEAR INFRARED ABSORBING PHOTOSENSITIZERS.", PROC. SPIE-INT. SOC. OPT. ENG. 1992, 1645 (PROC. OPT. METHODS TUMOR TREAT. DETECT.: MECH. TECH. PHOTODYN. THER. 1992,, pages 259 - 260 * |
IVERSON, BRENT L. ET AL.: "INTERACTIONS BETWEEN PORPHYRINS AND NUCLEIC ACIDS.", PURE APPLIED CHEMISTRY, vol. 66, no. 4, 1994, pages 845 - 850 * |
J. L. SESSLER ET AL.: "GADOLINIUM (III) TEXAPHYRIN: A NOVEL MRI CONTRAST AGENT.", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 115, no. 22, November 1993 (1993-11-01), WASHINGTON, DC US, pages 10368 - 10369, XP000500107, DOI: doi:10.1021/ja00075a066 * |
J. L.SESSLER ET AL.: "TEXAPHYRINS: SYNTHESIS AND APPLICATIONS", ACCOUNTS OF CHEMICAL RESEARCH, vol. 27, February 1994 (1994-02-01), WASHINGTON US, pages 43 - 50, XP000420352, DOI: doi:10.1021/ar00038a002 * |
KOENIG K. ET AL., INT. CONGRESS SERIES, NO 1011. PHOTODYNAMIC THERAPY AND BIOMEDICAL LASERS; INT. CONFERENCE, MILAN ITALY, JUNE 24-27, 1992. XXV+1014P. EXCERPTA MEDICA, AMSTERDAM, NETHERLANDS, 24 June 1992 (1992-06-24), pages 802 - 805 * |
MATTHEWS, J. L. ET AL.: "INACTIVATION OF VIRUSES WITH PHOTOACTIVE COMPOUNDS.", BLOOD CELLS, vol. 18, no. 1, 1992, pages 75 - 89, XP000943731 * |
MODY T. D. ET AL., 22ND ANNUAL MEETING OF THE AMERICAN SOCIETY FOR PHOTOBIOLOGY, PHOTOCHEMISTRY AND PHOTOBIOLOGY 59 (SPEC. ISSUE), 1994, SCOTTSDALE, ARIZONA, USA, * |
YOUNG SW. ET AL.: "PRECLINCAL EVALUATION OF GADOLINIUM (III) TEXAPHYRIN COMPLEX. A NEW PARAMAGNETIC CONTRAST AGENT FOR MRI.", INVEST. RADIOL., vol. 29, no. 3, March 1994 (1994-03-01), pages 330 - 338 * |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
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DE19646762B4 (en) * | 1996-11-04 | 2004-05-13 | Schering Ag | Use of metal compounds for the production of agents for radiotherapy of tumors |
US6022526A (en) * | 1997-07-30 | 2000-02-08 | Pharmacyclics, Inc. | Use of texaphyrins in detection of melanin and melanin metabolites diagnostic of melanotic melanoma |
WO1999016474A1 (en) * | 1997-09-26 | 1999-04-08 | Schering Aktiengesellschaft | Lipophilic metal complexes for necrosis and infarct imaging |
WO2000001698A1 (en) * | 1998-07-03 | 2000-01-13 | Schering Aktiengesellschaft | Porphyrin derivatives and their use in photodynamic therapy and mri diagnosis |
WO2001032210A3 (en) * | 1999-10-29 | 2002-02-07 | Pharmacyclics Inc | Compositions for treating atheroma and neoplastic tissue |
US6638924B2 (en) | 2000-08-30 | 2003-10-28 | Pharmacyclics, Inc. | Metallotexaphyrin derivatives |
US7112671B2 (en) | 2000-08-30 | 2006-09-26 | Pharmacyclics, Inc. | Non-symmetric tripyrranes in the synthesis of novel macrocycles |
US7449454B2 (en) | 2000-08-30 | 2008-11-11 | Pharmacyclics, Inc. | Metallotexaphyrin derivatives |
US6723750B2 (en) | 2002-03-15 | 2004-04-20 | Allergan, Inc. | Photodynamic therapy for pre-melanomas |
EP1704870A1 (en) | 2005-03-25 | 2006-09-27 | Nipro Corporation | Use of iron compounds as radiosensitizers |
US8410263B2 (en) | 2005-09-26 | 2013-04-02 | Pharmacyclics, Inc. | High-purity texaphyrin metal complexes |
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EP0724457B1 (en) | 2003-03-05 |
US5622946A (en) | 1997-04-22 |
ES2193163T3 (en) | 2003-11-01 |
JP3596816B2 (en) | 2004-12-02 |
NO961436D0 (en) | 1996-04-11 |
EP0724457A1 (en) | 1996-08-07 |
US5801229A (en) | 1998-09-01 |
JP2004091495A (en) | 2004-03-25 |
US5632970A (en) | 1997-05-27 |
CA2173319C (en) | 2008-03-25 |
DE69432221T2 (en) | 2003-12-04 |
NZ275217A (en) | 2001-06-29 |
KR100365058B1 (en) | 2003-05-09 |
US6069140A (en) | 2000-05-30 |
NO961436L (en) | 1996-06-11 |
KR960704582A (en) | 1996-10-09 |
JPH09508616A (en) | 1997-09-02 |
DE69432221D1 (en) | 2003-04-10 |
US5580543A (en) | 1996-12-03 |
US5583220A (en) | 1996-12-10 |
US5457183A (en) | 1995-10-10 |
DK0724457T3 (en) | 2003-06-30 |
SG48392A1 (en) | 1998-04-17 |
PT724457E (en) | 2003-07-31 |
ATE233575T1 (en) | 2003-03-15 |
AU683316B2 (en) | 1997-11-06 |
NO315185B1 (en) | 2003-07-28 |
CA2173319A1 (en) | 1995-04-20 |
AU8075694A (en) | 1995-05-04 |
US5587371A (en) | 1996-12-24 |
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