WO2013151672A2 - Modified polynucleotides for the production of oncology-related proteins and peptides - Google Patents

Modified polynucleotides for the production of oncology-related proteins and peptides Download PDF

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Publication number
WO2013151672A2
WO2013151672A2 PCT/US2013/030070 US2013030070W WO2013151672A2 WO 2013151672 A2 WO2013151672 A2 WO 2013151672A2 US 2013030070 W US2013030070 W US 2013030070W WO 2013151672 A2 WO2013151672 A2 WO 2013151672A2
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WO
WIPO (PCT)
Prior art keywords
cancer
oncology
isolated polynucleotide
thio
guanosine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2013/030070
Other languages
English (en)
French (fr)
Other versions
WO2013151672A3 (en
Inventor
Stephane Bancel
Tirtha Chakraborty
Antonin De Fougerolles
Sayda M. ELBASHIR
Matthias John
Atanu Roy
Susan Whoriskey
Kristy M. WOOD
Paul Hatala
Jason P. SCHRUM
Kenechi Ejebe
Jeff Lynn Ellsworth
Justin Guild
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Moderna Inc
Original Assignee
Moderna Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=49235350&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2013151672(A2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Moderna Therapeutics Inc filed Critical Moderna Therapeutics Inc
Priority to EP13772721.0A priority Critical patent/EP2833892A4/en
Priority to CA2868393A priority patent/CA2868393A1/en
Priority to JP2015504571A priority patent/JP2015518816A/ja
Priority to HK15107391.3A priority patent/HK1206636A1/xx
Priority to AU2013243955A priority patent/AU2013243955B2/en
Priority to US14/390,106 priority patent/US9221891B2/en
Priority to JP2015504587A priority patent/JP6348482B2/ja
Priority to CN202010645626.3A priority patent/CN112390871A/zh
Priority to AU2013243834A priority patent/AU2013243834A1/en
Priority to CN201380028186.5A priority patent/CN104870022B/zh
Priority to HK15107400.2A priority patent/HK1206639B/en
Priority to EP13713306.2A priority patent/EP2833922B1/en
Priority to EP18204317.4A priority patent/EP3520820A1/en
Priority to PCT/US2013/031821 priority patent/WO2013151736A2/en
Priority to CA2868418A priority patent/CA2868418A1/en
Publication of WO2013151672A2 publication Critical patent/WO2013151672A2/en
Priority to US14/107,105 priority patent/US9255129B2/en
Priority to US14/107,053 priority patent/US9216205B2/en
Priority to US14/107,079 priority patent/US9149506B2/en
Priority to US14/106,988 priority patent/US9301993B2/en
Priority to US14/107,029 priority patent/US20140113959A1/en
Publication of WO2013151672A3 publication Critical patent/WO2013151672A3/en
Anticipated expiration legal-status Critical
Priority to US14/824,247 priority patent/US9572896B2/en
Priority to US15/015,684 priority patent/US9587003B2/en
Priority to US15/403,517 priority patent/US10493167B2/en
Priority to JP2017012947A priority patent/JP6953135B6/ja
Priority to US15/425,813 priority patent/US10501513B2/en
Priority to AU2017232121A priority patent/AU2017232121B2/en
Priority to AU2018200377A priority patent/AU2018200377A1/en
Priority to AU2019202835A priority patent/AU2019202835A1/en
Priority to US16/442,168 priority patent/US10583203B2/en
Priority to US16/707,998 priority patent/US20200247861A1/en
Priority to JP2019225097A priority patent/JP2020072670A/ja
Priority to US16/811,648 priority patent/US20210077634A1/en
Priority to AU2020257150A priority patent/AU2020257150A1/en
Priority to JP2022020499A priority patent/JP2022078081A/ja
Priority to AU2023263451A priority patent/AU2023263451A1/en
Priority to JP2024018721A priority patent/JP2024063025A/ja
Priority to US18/592,122 priority patent/US20250074962A1/en
Ceased legal-status Critical Current

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Definitions

  • PCT/US 13/XXXXX entitled Modified Polynucleotides for the Production of Nuclear Proteins
  • Attorney Docket Number M309.20 PCT/US 13/XXXXX
  • Modified Polynucleotides for the Production of Proteins Attorney Docket Number M310.20
  • PCT/US 13/XXXXX entitled Modified Polynucleotides for the Production of Proteins Associated with Human Disease
  • the invention relates to compositions, methods, processes, kits and devices for the design, preparation, manufacture and/or formulation of oncology-ralted polynucleotides, primary constructs and modified mRNA molecules (mmRNA). BACKGROUND OF THE INVENTION
  • Cancer is a disease characterized by uncontrolled cell division and growth within the body. In the United States, roughly a third of all women and half of all men will experience cancer in their lifetime. Polypeptides are involved in every aspect of the disease including cancer cell biology (carcinogenesis, cell cycle suppression, DNA repair and angiogenesis), treatment (immunotherapy, hormone manipulation, enzymatic inhibition), diagnosis and determination of cancer type (molecular markers for breast, prostate, colon and cervical cancer for example). With the host of undesired
  • nucleic acid based compounds or polynucleotide-encoding nucleic acid-based compounds e.g., modified mRNA or mmRNA
  • nucleic acid-based compounds e.g., modified mRNA or mmRNA
  • compositions, methods, processes, kits and devices for the design, preparation, manufacture and/or formulation of modified mRNA (mmRNA) molecules encoding at least one oncology-related polypeptide of interest are described herein.
  • the present invention provides a method of treating a disease, disorder and/or condition in a subject in need thereof by increasing the level of an oncology-related polypeptide of interest comprising administering to said subject an isolated
  • the disease, disorder and/or condition may include, but is not limited to, adrenal cortical cancer, advanced cancer, anal cancer, aplastic anemia, bileduct cancer, bladder cancer, bone cancer, bone metastasis, brain tumors, brain cancer, breast cancer, childhood cancer, cancer of unknown primary origin, Castleman disease, cervical cancer, colon/rectal cancer, endometrial cancer, esophagus cancer, Ewing family of tumors, eye cancer, gallbladder cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, gestational trophoblastic disease, Hodgkin disease, Kaposi sarcoma, renal cell carcinoma, laryngeal and hypopharyngeal cancer, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia, liver cancer, non-small cell lung cancer,
  • myelodysplasia syndrome nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-Hodgkin lymphoma, oral cavity and oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, penile cancer, pituitary tumors, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcoma in adult soft tissue, basal and squamous cell skin cancer, melanoma, small intestine cancer, stomach cancer, testicular cancer, throat cancer, thymus cancer, thyroid cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Waldenstrom macroglobulinemia, Wilms tumor and secondary cancers caused by cancer treatment.
  • the present invention provides a method of reducing, eliminating,or preventing tumor growth in a subject in need thereof by increasing the level of an oncology-related polypeptide of interest comprising administering to said subject an isolated polynucleotide encoding said oncology-related polypeptide.
  • the tumor growth may be associated with or results from a disease, disorder and/or condition such as, but not limited to, adrenal cortical cancer, advanced cancer, anal cancer, aplastic anemia, bileduct cancer, bladder cancer, bone cancer, bone metastasis, brain tumors, brain cancer, breast cancer, childhood cancer, cancer of unknown primary origin, Castleman disease, cervical cancer, colon/rectal cancer, endometrial cancer, esophagus cancer, Ewing family of tumors, eye cancer, gallbladder cancer, gastrointestinal carcinoid tumors,
  • a disease, disorder and/or condition such as, but not limited to, adrenal cortical cancer, advanced cancer, anal cancer, aplastic anemia, bileduct cancer, bladder cancer, bone cancer, bone metastasis, brain tumors, brain cancer, breast cancer, childhood cancer, cancer of unknown primary origin, Castleman disease, cervical cancer, colon/rectal cancer, endometrial cancer, esophagus cancer, Ewing family of tumors, eye cancer, gallbladder cancer,
  • gastrointestinal stromal tumors gestational trophoblastic disease, Hodgkin disease, Kaposi sarcoma, renal cell carcinoma, laryngeal and hypopharyngeal cancer, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia, liver cancer, non-small cell lung cancer, small cell lung cancer, lung carcinoid tumor, lymphoma of the skin, malignant mesothelioma, multiple myeloma, myelodysplasia syndrome, nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-Hodgkin lymphoma, oral cavity and oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, penile cancer, pituitary tumors, prostate cancer, retinoblastoma, rhabdomyos
  • the present invention provides a method of reducing and/or ameriorating at least on symptom of cancer in a subject in need thereof by increasing the level of an oncology-related polypeptide of interest comprising administering to said subject an isolated polynucleotide encoding said oncology-related polypeptide.
  • the present invention provides an isolated polynucleotide comprising a first region of linked nucleosides, said first region encoding the oncology-related polypeptide of interest, a first flanking region located at the 5 ' terminus of said first region comprising a sequence of linked nucleosides selected from the group consisting of the native 5 ' untranslated region (UTR) of any of SEQ ID NOs: 4704-9203, SEQ ID NOs: 1-4 and functional variants thereof and a second flanking region located at the 3 ' terminus of said first region comprising a sequence of linked nucleosides selected from the group consisting of the native 3' UTR of any of SEQ ID NOs: 4704-9203, SEQ ID NOs: 5-21 and functional variants thereof and a 3' tailing sequence of linked nucleosides.
  • the isolated polynucleotide may further be substantially purified.
  • the first region of the isolated polynucleotides of the present may comprise two stop codons.
  • the first region further comprises a first stop codon "TGA” and a second stop codon selected from the group consisting of "TAA,” “TGA” and “TAG.”
  • the 3' tailing sequence of the isolated polynucleotides of the present invention may further include linked nucleosides such as, but not limitd to, a poly-A tail of approximately 130 nucleotides and a poly A-G quartet.
  • the first flanking region of the isolated polynucleotide may further comprise at least one 5' terminal cap such as, but not limited to, CapO, Capl, ARC A, inosine, Nl- methyl-guanosine, 2'fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino- guanosine, LNA-guanosine, and 2-azido-guanosine.
  • 5' terminal cap such as, but not limited to, CapO, Capl, ARC A, inosine, Nl- methyl-guanosine, 2'fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino- guanosine, LNA-guanosine, and 2-azido-guanosine.
  • the nucleotides of the isolated polynucleotides of the present invention may comprise at least two modifications and a translatable region.
  • the modification may be on at least one nucleoside and/or the backbone of said nucleotides, on both a nucleoside and a backbone linkage or on a sugar of the nucleoside.
  • the modification may comprise replacing at least one phosphodiester linkage with a phosphorothioate linkage.
  • the modification may include, but are not limited to, pyridin-4-one ribonucleoside, 5-aza- uridine, 2-thio-5-aza-uridine, 2-thiouridine, 4-thio-pseudouridine, 2-thio-pseudouridine,
  • 6- diaminopurine 7-deaza-adenine, 7-deaza-8-aza-adenine, 7-deaza-2-aminopurine, 7- deaza-8-aza-2-aminopurine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6- diaminopurine, 1-methyladenosine, N6-methyladenosine, N6-isopentenyladenosine, N6- (cis-hydroxyisopentenyl)adenosine, 2-methylthio-N6-(cis-hydroxyisopentenyl) adenosine, N6-glycinylcarbamoyladenosine, N6-threonylcarbamoyladenosine, 2- methylthio-N6-threonyl carbamoyladenosine, N6,N6-dimethyladenosine, 7- methyladenine, 2-methylthio-aden
  • the isolated polynucleotides of the present invention may be formulated.
  • the formulation may comprise a lipid which may include, but is not limited to, DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3 -DMA, PLGA, PEG, PEG-DMG, PEGylated lipids and mixtures thereof.
  • the isolated polynucleotides of the present invention may be administered at a total daily dose of between 0.001 ug and 150 ug.
  • the administration may be by injection, topical administration, ophthalmic administration and intranasal administration.
  • the injection may include injections such as, but not limited to, intradermal, subcutaneous and intramuscular.
  • the topical administration may be, but is not limited to, a cream, lotion, ointment, gel, spray, solution and the like.
  • the topical administration may further include a penetration enhancer such as, but not limited to, surfactants, fatty acids, bile salts, chelating agents, non-chelating non-surfactants, polyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether, fatty acids and/or salts in combination with bile acids and/or salts, sodium salt in combination with lauric acid, capric acid and UDCA, and the like.
  • a penetration enhancer such as, but not limited to, surfactants, fatty acids, bile salts, chelating agents, non-chelating non-surfactants, polyoxyethylene-9-lauryl ether, polyoxyethylene-20-cetyl ether, fatty acids and/or salts in combination with bile acids and/or salts, sodium salt in combination with lauric acid, capric acid and UDCA, and the like.
  • the isolated polynucleotide formulation may further include a
  • pharmaceutically acceptable excipient such as, but not limited to, a solvent, aqueous solvent, non-aqueous solvent, dispersion media, diluent, dispersion, suspension aid, surface active agent, isotonic agent, thickening or emulsifying agent, preservative, lipid, lipidoids liposome, lipid nanoparticle, core-shell nanoparticles, polymer, lipoplex, peptide, protein, cell, hyaluronidase, and mixtures thereof.
  • a solvent aqueous solvent, non-aqueous solvent, dispersion media, diluent, dispersion, suspension aid, surface active agent, isotonic agent, thickening or emulsifying agent, preservative, lipid, lipidoids liposome, lipid nanoparticle, core-shell nanoparticles, polymer, lipoplex, peptide, protein, cell, hyaluronidase, and mixtures thereof.
  • FIG. 1 is a schematic of an oncology related-primary construct of the present invention.
  • FIG. 2 illustrates lipid structures in the prior art useful in the present invention. Shown are the structures for 98N12-5 (TETA5-LAP), DLin-DMA, DLin-K- DMA (2,2-Dilinoleyl-4-dimethylaminomethyl-[ 1 ,3]-dioxolane), DLin-KC2-DMA, DLin-MC3-DMA and C12-200.
  • FIG. 3 is a representative plasmid useful in the IVT reactions taught herein.
  • the plasmid contains Insert 64818, designed by the instant inventors.
  • FIG. 4 is a gel profile of modified mR A encapsulated in PLGA
  • compositions including pharmaceutical compositions
  • polynucleotides encoding one or more oncology-related polypeptides of interest are also provided. Also provided are systems, processes, devices and kits for the selection, design and/or utilization of the polynucleotides encoding the oncology-related polypeptides of interest described herein.
  • these oncology-related polynucleotides are preferably modified as to avoid the deficiencies of other polypeptide-encoding molecules of the art. Hence these polynucleotides are referred to as modified mRNA or mmRNA.
  • 61/519,158 filed May 17, 2011 teaching veterinary applications of mmRNA technology; 61/533, 537 filed on September 12, 2011 teaching antimicrobial applications of mmRNA technology; 61/533,554 filed on September 12, 2011 teaching viral applications of mmRNA technology, 61/542,533 filed on October 3, 2011 teaching various chemical modifications for use in mmRNA technology; 61/570,690 filed on December 14, 2011 teaching mobile devices for use in making or using mmRNA technology; 61/570,708 filed on December 14, 2011 teaching the use of mmRNA in acute care situations;
  • oncology-related polynucleotides oncology- related primary constructs and/or oncology-related mmR A encoding oncology-related polypeptides of interest which have been designed to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, m NA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency (when applicable), accessibility to circulation, protein half-life and/or modulation of a cell's status, function and/or activity.
  • compositions of the Invention (mmRNA)
  • nucleic acid molecules specifically oncology- related polynucleotides, oncology-related primary constructs and/or oncology-related mmRNA which encode one or more oncology-related polypeptides of interest.
  • nucleic acid in its broadest sense, includes any compound and/or substance that comprise a polymer of nucleotides. These polymers are often referred to as
  • nucleic acids or polynucleotides of the invention include, but are not limited to, ribonucleic acids (RNAs), deoxyribonucleic acids (DNAs), threose nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic acids (PNAs), locked nucleic acids (LNAs, including LNA having a ⁇ - D-ribo configuration, a-LNA having an a-L-ribo configuration (a diastereomer of LNA), 2'-amino-LNA having a 2'-amino functionalization, and 2'-amino- a-LNA having a 2'-amino functionalization) or hybrids thereof.
  • RNAs ribonucleic acids
  • DNAs deoxyribonucleic acids
  • TAAs threose nucleic acids
  • GNAs glycol nucleic acids
  • PNAs peptide nucleic acids
  • LNAs locked
  • the nucleic acid molecule is a messenger RNA (mRNA).
  • mRNA messenger RNA
  • the term "messenger RNA” (mRNA) refers to any oncology- related polynucleotide which encodes an oncology-related polypeptide of interest and which is capable of being translated to produce the encoded oncology-related polypeptide of interest in vitro, in vivo, in situ or ex vivo.
  • the basic components of an mRNA molecule include at least a coding region, a 5'UTR, a 3'UTR, a 5' cap and a poly-A tail.
  • the present invention expands the scope of functionality of traditional mRNA molecules by providing oncology-related polynucleotides or oncology-related primary RNA constructs which maintain a modular organization, but which comprise one or more structural and/or chemical modifications or alterations which impart useful properties to the polynucleotide including, in some embodiments, the lack of a substantial induction of the innate immune response of a cell into which the oncology-related polynucleotide is introduced.
  • modified mRNA molecules of the present invention are termed "mmR A.”
  • a "structural" feature or modification is one in which two or more linked nucleotides are inserted, deleted, duplicated, inverted or randomized in an oncology-related polynucleotide, oncology-related primary construct or oncology-related mmRNA without significant chemical modification to the nucleotides themselves. Because chemical bonds will necessarily be broken and reformed to effect a structural modification, structural modifications are of a chemical nature and hence are chemical modifications. However, structural modifications will result in a different sequence of nucleotides. For example, the polynucleotide "ATCG” may be chemically modified to "AT-5meC-G".
  • the same polynucleotide may be structurally modified from "ATCG” to "ATCCCG".
  • the dinucleotide "CC” has been inserted, resulting in a structural modification to the oncology-related polynucleotide.
  • the mmRNA of the present invention are distinguished from wild type mRNA in their functional and/or structural design features which serve to, as evidenced herein, overcome existing problems of effective polypeptide production using nucleic acid-based therapeutics.
  • Figure 1 shows a representative polynucleotide primary construct 100 of the present invention.
  • the term "primary construct” or “primary mRNA construct” refers to an oncology-related polynucleotide transcript which encodes one or more oncology-related polypeptides of interest and which retains sufficient structural and/or chemical features to allow the oncology-related polypeptide of interest encoded therein to be translated.
  • Oncology-related primary constructs may be oncology-related polynucleotides of the invention. When structurally or chemically modified, the oncology-related primary construct may be referred to as an oncology-related mmRNA.
  • the oncology-related primary construct 100 here contains a first region of linked nucleotides 102 that is flanked by a first flanking region 104 and a second flaking region 106.
  • the "first region” may be referred to as a "coding region” or “region encoding” or simply the "first region.”
  • This first region may include, but is not limited to, the encoded oncology-related polypeptide of interest.
  • the oncology-related polypeptide of interest may comprise at its 5 ' terminus one or more signal sequences encoded by a signal sequence region 103.
  • the flanking region 104 may comprise a region of linked nucleotides comprising one or more complete or incomplete 5' UTRs sequences.
  • the flanking region 104 may also comprise a 5' terminal cap 108.
  • the second flanking region 106 may comprise a region of linked nucleotides comprising one or more complete or incomplete 3' UTRs.
  • the flanking region 106 may also comprise a 3' tailing sequence 110.
  • first operational region 105 Bridging the 5' terminus of the first region 102 and the first flanking region 104 is a first operational region 105.
  • this operational region comprises a start codon.
  • the operational region may alternatively comprise any translation initiation sequence or signal including a start codon.
  • this operational region comprises a stop codon.
  • the operational region may alternatively comprise any translation initiation sequence or signal including a stop codon. According to the present invention, multiple serial stop codons may also be used.
  • the operation region of the present invention may comprise two stop codons.
  • the first stop codon may be "TGA” and the second stop codon may be selected from the group consisting of "TAA,” "TGA” and "TAG.”
  • the shortest length of the first region of the oncology-related primary construct of the present invention can be the length of a nucleic acid sequence that is sufficient to encode for a dipeptide, a tripeptide, a tetrapeptide, a pentapeptide, a hexapeptide, a heptapeptide, an octapeptide, a nonapeptide, or a decapeptide.
  • the length may be sufficient to encode a peptide of 2-30 amino acids, e.g. 5- 30, 10-30, 2-25, 5-25, 10-25, or 10-20 amino acids.
  • the length may be sufficient to encode for a peptide of at least 11, 12, 13, 14, 15, 17, 20, 25 or 30 amino acids, or a peptide that is no longer than 40 amino acids, e.g. no longer than 35, 30, 25, 20, 17, 15, 14, 13, 12, 11 or 10 amino acids.
  • the length of the first region encoding the oncology-related polypeptide of interest of the present invention is greater than about 30 nucleotides in length (e.g., at least or greater than about 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, and 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000 or up to and including 100,000 nucleotides).
  • the "first region” may be referred to as a "coding region” or "region encoding” or simply the "first region.”
  • the oncology-related polynucleotide, oncology-related primary construct, or oncology-related mmRNA includes from about 30 to about 100,000 nucleotides (e.g., from 30 to 50, from 30 to 100, from 30 to 250, from 30 to 500, from 30 to 1,000, from 30 to 1,500, from 30 to 3,000, from 30 to 5,000, from 30 to 7,000, from 30 to 10,000, from 30 to 25,000, from 30 to 50,000, from 30 to 70,000, from 100 to 250, from 100 to 500, from 100 to 1,000, from 100 to 1,500, from 100 to 3,000, from 100 to 5,000, from 100 to 7,000, from 100 to 10,000, from 100 to 25,000, from 100 to 50,000, from 100 to 70,000, from 100 to 100,000, from 500 to 1,000, from 500 to 1,500, from 500 to 2,000, from 500 to 3,000, from 500 to 5,000, from 500 to 7,000, from 500 to 10,000, from 500 to 25,000, from 500 to 50,000, from 500 to 70,000,
  • the first and second flanking regions may range independently from 15-1,000 nucleotides in length (e.g., greater than 30, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, and 900 nucleotides or at least 30, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, and 1,000 nucleotides).
  • 15-1,000 nucleotides in length e.g., greater than 30, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, and 1,000 nucleotides.
  • the tailing sequence may range from absent to 500 nucleotides in length (e.g., at least 60, 70, 80, 90, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, or 500 nucleotides).
  • the length may be determined in units of or as a function of polyA binding protein binding.
  • the polyA tail is long enough to bind at least 4 monomers of polyA binding protein.
  • PolyA binding protein monomers bind to stretches of approximately 38 nucleotides. As such, it has been observed that polyA tails of about 80 nucleotides and 160 nucleotides are functional.
  • the capping region may comprise a single cap or a series of nucleotides forming the cap.
  • the capping region may be from 1 to 10, e.g. 2-9, 3-8, 4-7, 1-5, 5-10, or at least 2, or 10 or fewer nucleotides in length.
  • the cap is absent.
  • the first and second operational regions may range from 3 to 40, e.g., 5-30, 10-20, 15, or at least 4, or 30 or fewer nucleotides in length and may comprise, in addition to a start and/or stop codon, one or more signal and/or restriction sequences.
  • an oncology-related primary construct or oncology-related mmRNA may be cyclized, or concatemerized, to generate a translation competent molecule to assist interactions between poly-A binding proteins and 5 '-end binding proteins.
  • the mechanism of cyclization or concatemerization may occur through at least 3 different routes: 1) chemical, 2) enzymatic, and 3) ribozyme catalyzed.
  • the newly formed 5 '-/3 '-linkage may be intramolecular or intermolecular.
  • the 5'-end and the 3'-end of the nucleic acid may contain chemically reactive groups that, when close together, form a new covalent linkage between the 5 '-end and the 3 '-end of the molecule.
  • the 5 '-end may contain an NHS-ester reactive group and the 3 '-end may contain a 3'-amino-terminated nucleotide such that in an organic solvent the 3'-amino-terminated nucleotide on the 3 '-end of a synthetic mRNA molecule will undergo a nucleophilic attack on the 5 '-NHS-ester moiety forming a new 5 '-/3 '-amide bond.
  • T4 RNA ligase may be used to enzymatically link a 5'- phosphorylated nucleic acid molecule to the 3'-hydroxyl group of a nucleic acid forming a new phosphorodiester linkage.
  • ⁇ g of a nucleic acid molecule is incubated at 37°C for 1 hour with 1-10 units of T4 RNA ligase (New England Biolabs, Ipswich, MA) according to the manufacturer's protocol.
  • the ligation reaction may occur in the presence of a split oligonucleotide capable of base-pairing with both the 5'- and 3'- region in juxtaposition to assist the enzymatic ligation reaction.
  • either the 5 '-or 3 '-end of the cDNA template encodes a ligase ribozyme sequence such that during in vitro transcription, the resultant nucleic acid molecule can contain an active ribozyme sequence capable of ligating the 5 '-end of a nucleic acid molecule to the 3 '-end of a nucleic acid molecule.
  • the ligase ribozyme may be derived from the Group I Intron, Group I Intron, Hepatitis Delta Virus, Hairpin ribozyme or may be selected by SELEX (systematic evolution of ligands by exponential enrichment).
  • the ribozyme ligase reaction may take 1 to 24 hours at temperatures between 0 and 37°C.
  • oncology-related polynucleotides may be linked together through the 3 '-end using nucleotides which are modified at the 3'- terminus.
  • Chemical conjugation may be used to control the stoichiometry of delivery into cells.
  • the glyoxylate cycle enzymes isocitrate lyase and malate synthase, may be supplied into HepG2 cells at a 1 : 1 ratio to alter cellular fatty acid metabolism.
  • This ratio may be controlled by chemically linking oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA using a 3'-azido terminated nucleotide on one oncology-related polynucleotide, oncology- related primary construct or oncology-related mmRNA species and a C5-ethynyl or alkynyl-containing nucleotide on the opposite oncology-related polynucleotide, oncology-related primary construct or oncology-related mmRNA species.
  • the modified nucleotide is added post-transcriptionally using terminal transferase (New England Biolabs, Ipswich, MA) according to the manufacturer's protocol.
  • the two oncology-related polynucleotide, oncology-related primary construct or oncology-related mmRNA species may be combined in an aqueous solution, in the presence or absence of copper, to form a new covalent linkage via a click chemistry mechanism as described in the literature.
  • oncology-related polynucleotides may be linked together using a functionalized linker molecule.
  • a functionalized saccharide molecule may be chemically modified to contain multiple chemical reactive groups (SH-, NH 2 -, N 3 , etc8) to react with the cognate moiety on a 3 '-functionalized oncology-related mRNA molecule (i.e., a 3'-maleimide ester, 3'-NHS-ester, alkynyl).
  • the number of reactive groups on the modified saccharide can be controlled in a stoichiometric fashion to directly control the stoichiometric ratio of conjugated oncology- related polynucleotide, oncology-related primary construct or oncology-related mmRNA.
  • oncology- related primary constructs or oncology-related mmRNA of the present invention can be designed to be conjugated to other polynucleotides, oncology-related polypeptides, dyes, intercalating agents ⁇ e.g. acridines), cross-linkers ⁇ e.g. psoralene, mitomycin C), porphyrins (TPPC4, texaphyrin, Sapphyrin), polycyclic aromatic hydrocarbons ⁇ e.g., phenazine, dihydrophenazine), artificial endonucleases ⁇ e.g.
  • alkylating agents phosphate, amino, mercapto, PEG ⁇ e.g., PEG-40K
  • MPEG MPEG
  • [MPEG] 2 polyamino, alkyl, substituted alkyl, radiolabeled markers, enzymes, haptens ⁇ e.g. biotin)
  • transport/absorption facilitators ⁇ e.g., aspirin, vitamin E, folic acid), synthetic
  • ribonucleases proteins, e.g., glycoproteins, or peptides, e.g., molecules having a specific affinity for a co-ligand, or antibodies e.g., an antibody, that binds to a specified cell type such as a cancer cell, endothelial cell, or bone cell, hormones and hormone receptors, non-peptidic species, such as lipids, lectins, carbohydrates, vitamins, cofactors, or a drug.
  • proteins e.g., glycoproteins, or peptides, e.g., molecules having a specific affinity for a co-ligand
  • antibodies e.g., an antibody, that binds to a specified cell type such as a cancer cell, endothelial cell, or bone cell
  • hormones and hormone receptors non-peptidic species, such as lipids, lectins, carbohydrates, vitamins, cofactors, or a drug.
  • Conjugation may result in increased stability and/or half life and may be particularly useful in targeting the oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA to specific sites in the cell, tissue or organism.
  • the oncology-related mmRNA or oncology-related primary constructs may be administered with, or further encode one or more of RNAi agents, siRNAs, shRNAs, miRNAs, miRNA binding sites, antisense RNAs, ribozymes, catalytic DNA, tRNA, RNAs that induce triple helix formation, aptamers or vectors, and the like.
  • RNAi agents siRNAs, shRNAs, miRNAs, miRNA binding sites, antisense RNAs, ribozymes, catalytic DNA, tRNA, RNAs that induce triple helix formation, aptamers or vectors, and the like.
  • bifunctional oncology-related polynucleotides e.g., bifunctional oncology-related primary constructs or oncology- related bifunctional mmRNA.
  • bifunctional oncology-related polynucleotides are those having or capable of at least two functions. These molecules may also by convention be referred to as multi-functional.
  • bifunctional oncology-related polynucleotides may be encoded by the RNA (the function may not manifest until the encoded product is translated) or may be a property of the polynucleotide itself. It may be structural or chemical.
  • Bifunctional modified oncology-related polynucleotides may comprise a function that is covalently or electrostatically associated with the polynucleotides.
  • the two functions may be provided in the context of a complex of a mmRNA and another molecule.
  • Bifunctional oncology-related polynucleotides may encode oncology-related peptides which are anti-proliferative. These peptides may be linear, cyclic, constrained or random coil. They may function as aptamers, signaling molecules, ligands or mimics or mimetics thereof. Anti-proliferative peptides may, as translated, be from 3 to 50 amino acids in length. They may be 5-40, 10-30, or approximately 15 amino acids long. They may be single chain, multichain or branched and may form complexes, aggregates or any multi-unit structure once translated.
  • oncology-related polynucleotides and oncology-related primary constructs having sequences that are partially or substantially not translatable, e.g., having a noncoding region.
  • Such noncoding region may be the "first region" of the oncology-related primary construct.
  • the noncoding region may be a region other than the first region.
  • Such molecules are generally not translated, but can exert an effect on protein production by one or more of binding to and sequestering one or more translational machinery components such as a ribosomal protein or a transfer RNA (tRNA), thereby effectively reducing protein expression in the cell or modulating one or more pathways or cascades in a cell which in turn alters protein levels.
  • tRNA transfer RNA
  • the oncology-related polynucleotide and/or oncology-related primary construct may contain or encode one or more long noncoding RNA (IncRNA, or lincRNA) or portion thereof, a small nucleolar RNA (sno-RNA), micro RNA (miRNA), small interfering RNA (siRNA) or Piwi-interacting RNA (piRNA).
  • IncRNA long noncoding RNA
  • lincRNA small nucleolar RNA
  • miRNA micro RNA
  • siRNA small interfering RNA
  • piRNA Piwi-interacting RNA
  • the oncology-related primary construct is designed to encode one or more oncology-related polypeptides of interest or fragments thereof.
  • An oncology-related polypeptide of interest may include, but is not limited to, whole polypeptides, a plurality of polypeptides or fragments of polypeptides, which independently may be encoded by one or more nucleic acids, a plurality of nucleic acids, fragments of nucleic acids or variants of any of the aforementioned.
  • the term "oncology-related polypeptides of interest” refers to any polypeptide which is selected to be encoded in the oncology-related primary construct of the present invention.
  • polypeptide means a polymer of amino acid residues (natural or unnatural) linked together most often by peptide bonds.
  • polypeptides include gene products, naturally occurring polypeptides, synthetic polypeptides, homologs, orthologs, paralogs, fragments and other equivalents, variants, and analogs of the foregoing.
  • a polypeptide may be a single molecule or may be a multi-molecular complex such as a dimer, trimer or tetramer. They may also comprise single chain or multichain
  • polypeptides such as antibodies or insulin and may be associated or linked. Most commonly disulfide linkages are found in multichain polypeptides.
  • polypeptide may also apply to amino acid polymers in which one or more amino acid residues are an artificial chemical analogue of a corresponding naturally occurring amino acid.
  • polypeptide variant refers to molecules which differ in their amino acid sequence from a native or reference sequence.
  • the amino acid sequence variants may possess substitutions, deletions, and/or insertions at certain positions within the amino acid sequence, as compared to a native or reference sequence.
  • variants will possess at least about 50% identity (homology) to a native or reference sequence, and preferably, they will be at least about 80%, more preferably at least about 90% identical (homologous) to a native or reference sequence.
  • variant mimics are provided.
  • the term “variant mimic” is one which contains one or more amino acids which would mimic an activated sequence.
  • glutamate may serve as a mimic for phosphoro- threonine and/or phosphoro-serine.
  • variant mimics may result in deactivation or in an inactivated product containing the mimic, e.g., phenylalanine may act as an inactivating substitution for tyrosine; or alanine may act as an inactivating substitution for serine.
  • homology as it applies to amino acid sequences is defined as the percentage of residues in the candidate amino acid sequence that are identical with the residues in the amino acid sequence of a second sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent homology. Methods and computer programs for the alignment are well known in the art. It is understood that homology depends on a calculation of percent identity but may differ in value due to gaps and penalties introduced in the calculation.
  • Analogs is meant to include polypeptide variants which differ by one or more amino acid alterations, e.g., substitutions, additions or deletions of amino acid residues that still maintain one or more of the properties of the parent or starting polypeptide.
  • compositions which are polypeptide based including variants and derivatives. These include substitutional, insertional, deletion and covalent variants and derivatives.
  • derivative is used synonymously with the term “variant” but generally refers to a molecule that has been modified and/or changed in any way relative to a reference molecule or starting molecule.
  • mmR A encoding oncology-related polypeptides containing substitutions, insertions and/or additions, deletions and covalent modifications with respect to reference sequences, in particular the oncology-related polypeptide sequences disclosed herein, are included within the scope of this invention.
  • sequence tags or amino acids can be added to the peptide sequences of the invention (e.g., at the N-terminal or C-terminal ends). Sequence tags can be used for peptide purification or localization. Lysines can be used to increase peptide solubility or to allow for biotinylation. Alternatively, amino acid residues located at the carboxy and amino terminal regions of the amino acid sequence of a peptide or protein may optionally be deleted providing for truncated sequences. Certain amino acids (e.g., C- terminal or N-terminal residues) may alternatively be deleted depending on the use of the sequence, as for example, expression of the sequence as part of a larger sequence which is soluble, or linked to a solid support.
  • amino acids e.g., C- terminal or N-terminal residues
  • substitutional variants when referring to polypeptides are those that have at least one amino acid residue in a native or starting sequence removed and a different amino acid inserted in its place at the same position.
  • the substitutions may be single, where only one amino acid in the molecule has been substituted, or they may be multiple, where two or more amino acids have been substituted in the same molecule.
  • conservative amino acid substitution refers to the substitution of an amino acid that is normally present in the sequence with a different amino acid of similar size, charge, or polarity.
  • conservative substitutions include the substitution of a non-polar (hydrophobic) residue such as isoleucine, valine and leucine for another non-polar residue.
  • conservative substitutions include the substitution of one polar (hydrophilic) residue for another such as between arginine and lysine, between glutamine and asparagine, and between glycine and serine.
  • substitution of a basic residue such as lysine, arginine or histidine for another, or the substitution of one acidic residue such as aspartic acid or glutamic acid for another acidic residue are additional examples of conservative substitutions.
  • non-conservative substitutions include the substitution of a non-polar (hydrophobic) amino acid residue such as isoleucine, valine, leucine, alanine, methionine for a polar (hydrophilic) residue such as cysteine, glutamine, glutamic acid or lysine and/or a polar residue for a non-polar residue.
  • “Insertional variants” when referring to polypeptides are those with one or more amino acids inserted immediately adjacent to an amino acid at a particular position in a native or starting sequence. "Immediately adjacent" to an amino acid means connected to either the alpha-carboxy or alpha-amino functional group of the amino acid.
  • deletional variants when referring to polypeptides are those with one or more amino acids in the native or starting amino acid sequence removed. Ordinarily, deletional variants will have one or more amino acids deleted in a particular region of the molecule.
  • Covalent derivatives when referring to polypeptides include modifications of a native or starting protein with an organic proteinaceous or non-proteinaceous derivatizing agent, and/or post-translational modifications. Covalent modifications are traditionally introduced by reacting targeted amino acid residues of the protein with an organic derivatizing agent that is capable of reacting with selected side-chains or terminal residues, or by harnessing mechanisms of post-translational modifications that function in selected recombinant host cells. The resultant covalent derivatives are useful in programs directed at identifying residues important for biological activity, for immunoassays, or for the preparation of anti-protein antibodies for immunoaffinity purification of the recombinant glycoprotein. Such modifications are within the ordinary skill in the art and are performed without undue experimentation.
  • polypeptides when referring to polypeptides are defined as distinct amino acid sequence-based components of a molecule.
  • Features of the polypeptides encoded by the mmRNA of the present invention include surface manifestations, local conformational shape, folds, loops, half-loops, domains, half-domains, sites, termini or any combination thereof.
  • manifestation refers to a polypeptide based component of a protein appearing on an outermost surface.
  • local conformational shape means a polypeptide based structural manifestation of a protein which is located within a definable space of the protein.
  • fold refers to the resultant conformation of an amino acid sequence upon energy minimization.
  • a fold may occur at the secondary or tertiary level of the folding process.
  • secondary level folds include beta sheets and alpha helices.
  • tertiary folds include domains and regions formed due to aggregation or separation of energetic forces.
  • Regions formed in this way include hydrophobic and hydrophilic pockets, and the like.
  • the term "turn” as it relates to protein conformation means a bend which alters the direction of the backbone of a peptide or polypeptide and may involve one, two, three or more amino acid residues.
  • loop refers to a structural feature of a polypeptide which may serve to reverse the direction of the backbone of a peptide or polypeptide. Where the loop is found in a polypeptide and only alters the direction of the backbone, it may comprise four or more amino acid residues. Oliva et al. have identified at least 5 classes of protein loops (J. Mol Biol 266 (4): 814- 830; 1997). Loops may be open or closed. Closed loops or "cyclic" loops may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10 or more amino acids between the bridging moieties.
  • Such bridging moieties may comprise a cysteine-cysteine bridge (Cys-Cys) typical in polypeptides having disulfide bridges or alternatively bridging moieties may be non-protein based such as the dibromozylyl agents used herein.
  • Cys-Cys cysteine-cysteine bridge
  • bridging moieties may be non-protein based such as the dibromozylyl agents used herein.
  • domain refers to a motif of a polypeptide having one or more identifiable structural or functional characteristics or properties (e.g., binding capacity, serving as a site for protein-protein interactions).
  • sub- domains may be identified within domains or half-domains, these subdomains possessing less than all of the structural or functional properties identified in the domains or half domains from which they were derived. It is also understood that the amino acids that comprise any of the domain types herein need not be contiguous along the backbone of the polypeptide (i.e., nonadjacent amino acids may fold structurally to produce a domain, half-domain or subdomain).
  • site As used herein when referring to polypeptides the terms "site” as it pertains to amino acid based embodiments is used synonymously with "amino acid residue” and "amino acid side chain.”
  • a site represents a position within a peptide or polypeptide that may be modified, manipulated, altered, derivatized or varied within the polypeptide based molecules of the present invention.
  • terminal refers to an extremity of a peptide or polypeptide. Such extremity is not limited only to the first or final site of the peptide or polypeptide but may include additional amino acids in the terminal regions.
  • the polypeptide based molecules of the present invention may be characterized as having both an N-terminus (terminated by an amino acid with a free amino group (NH2)) and a C -terminus (terminated by an amino acid with a free carboxyl group (COOH)).
  • Proteins of the invention are in some cases made up of multiple polypeptide chains brought together by disulfide bonds or by non- covalent forces (multimers, oligomers). These sorts of proteins will have multiple N- and C-termini.
  • the termini of the polypeptides may be modified such that they begin or end, as the case may be, with a non-polypeptide based moiety such as an organic conjugate.
  • any of the features have been identified or defined as a desired component of a polypeptide to be encoded by the oncology-related primary construct or oncology-related mmRNA of the invention, any of several manipulations and/or modifications of these features may be performed by moving, swapping, inverting, deleting, randomizing or duplicating. Furthermore, it is understood that manipulation of features may result in the same outcome as a modification to the molecules of the invention. For example, a manipulation which involved deleting a domain would result in the alteration of the length of a molecule just as modification of a nucleic acid to encode less than a full length molecule would.
  • the oncology-related polypeptides may comprise a consensus sequence which is discovered through rounds of experimentation.
  • a "consensus" sequence is a single sequence which represents a collective population of sequences allowing for variability at one or more sites.
  • protein fragments, functional protein domains, and homologous proteins are also considered to be within the scope of oncology-related polypeptides of interest of this invention.
  • any protein fragment meaning an oncology-related polypeptide sequence at least one amino acid residue shorter than a reference oncology-related polypeptide sequence but otherwise identical
  • a reference oncology-related protein 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or greater than 100 amino acids in length.
  • any oncology- related protein that includes a stretch of about 20, about 30, about 40, about 50, or about 100 amino acids which are about 40%, about 50%>, about 60%>, about 70%>, about 80%>, about 90%), about 95%, or about 100% identical to any of the sequences described herein can be utilized in accordance with the invention.
  • a polypeptide to be utilized in accordance with the invention includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more mutations as shown in any of the sequences provided or referenced herein.
  • the oncology-related primary constructs or oncology-related mmRNA of the present invention may be designed to encode oncology-related polypeptides of interest such as oncology -related peptides and proteins.
  • oncology-related primary constructs or oncology-related mmRNA of the present invention may encode variant polypeptides which have a certain identity with a reference oncology-related polypeptide sequence.
  • a "reference oncology-related polypeptide sequence" refers to a starting oncology-related polypeptide sequence. Reference sequences may be wild type sequences or any sequence to which reference is made in the design of another sequence.
  • a “reference polypeptide sequence” may, e.g., be any one of SEQ ID NOs: 4704-9203 as disclosed herein, e.g., any of SEQ ID NOs 4704, 4705, 4706, 4707, 4708, 4709, 4710, 471 1 , 4712, 4713, 4714, 4715, 4716, 4717, 4718, 4719, 4720, 4721 , 4722, 4723, 4724, 4725, 4726, 4727, 4728, 4729, 4730, 4731 , 4732, 4733, 4734, 4735, 4736, 4737, 4738, 4739, 4740, 4741 , 4742, 4743, 4744, 4745, 4746, 4747, 4748, 4749 4750, 4751, 4752, 4753, 4754, 4755, 4756,
  • identity refers to a relationship between the sequences of two or more peptides, as determined by comparing the sequences. In the art, identity also means the degree of sequence relatedness between peptides, as determined by the number of matches between strings of two or more amino acid residues. Identity measures the percent of identical matches between the smaller of two or more sequences with gap alignments (if any) addressed by a particular mathematical model or computer program (i.e., "algorithms"). Identity of related peptides can be readily calculated by known methods. Such methods include, but are not limited to, those described in
  • the polypeptide variant may have the same or a similar activity as the reference oncology-related polypeptide.
  • the variant may have an altered activity (e.g., increased or decreased) relative to a reference oncology- related polypeptide.
  • variants of a particular oncology-related polynucleotide or oncology-related polypeptide of the invention will have at least about 40%, 45%, 50%>, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%o, 99% but less than 100% sequence identity to that particular reference oncology- related polynucleotide or oncology-related polypeptide as determined by sequence alignment programs and parameters described herein and known to those skilled in the art.
  • Such tools for alignment include those of the BLAST suite (Stephen F. Altschul, Thomas L. Madden, Alejandro A.
  • Default parameters in the BLAST algorithm include, for example, an expect threshold of 10, Word size of 28, Match/Mismatch Scores 1, -2, Gap costs Linear. Any filter can be applied as well as a selection for species specific repeats, e.g., Homo sapiens.
  • the oncology-related polynucleotides, oncology-related primary constructs and/or oncology-related mmRNA may be used to treat a disease, disorder and/or condition in a subject.
  • the oncology-related polynucleotides, oncology-related primary constructs and/or oncology-related mmRNA may be used to reduce, eliminate or prevent tumor growth in a subject.
  • the oncology-related polynucleotides, oncology-related primary constructs and/or oncology-related mmRNA may be used to recude and/or ameliorate at least one symptom of cancer in a subject.
  • a symptom of cancer may include, but is not limited to, weakness, aches and pains, fever, fatigue, weight loss, blood clots, increased blood calcium levels, low white blood cell count, short of breath, dizziness, headaches, hyperpigmentation, jaundice, erthema, pruritis, excessive hair growth, change in bowel habits, change in bladder function, long-lasting sores, white patches inside the mouth, white spots on the tongue, unusual bleeding or discharge, thickening or lump on parts of the body, indigestion, trouble swallowing, changes in warts or moles, change in new skin and nagging cough or hoarseness.
  • oncology-related polynucleotides, oncology-related primary constructs and/or oncology- related mmRNA may reduce a side-effect associated with cancer such as, but not limited to, chemo brain, peripheral neuropathy, fatigue, depression, nausea, vomiting, pain, anemia, lymphedema, infections, sexual side effects, reduced fertility or infertility, ostomies, insomnia and hair loss.
  • chemo brain peripheral neuropathy, fatigue, depression, nausea, vomiting, pain, anemia, lymphedema, infections, sexual side effects, reduced fertility or infertility, ostomies, insomnia and hair loss.
  • Oncology-related proteins or oncology-related peptides may reduce a side-effect associated with cancer such as, but not limited to, chemo brain, peripheral neuropathy, fatigue, depression, nausea, vomiting, pain, anemia, lymphedema, infections, sexual side effects, reduced fertility or infertility, ostomies, insomnia and hair loss.
  • the oncology-related primary constructs or oncology-related mmRNA disclosed herein may encode one or more validated or "in testing" oncology-related proteins or oncology-related peptides.
  • one or more oncology-related proteins or oncology-related peptides currently being marketed or in development may be encoded by the oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the present invention. While not wishing to be bound by theory, it is believed that incorporation into the oncology-related primary constructs or oncology-related mmRNA of the invention will result in improved therapeutic efficacy due at least in part to the specificity, purity and selectivity of the construct designs.
  • the oncology-related polynucleotides, oncology-related primary constructs and/or oncology-related mmRNA may alter a biological and/or physiolocial process and/or compound such as, but not limited to, the cell cycle, the DNA damage response (e.g., DNA damage repair), apoptosis, angiogenesis, cell motility, the epithelial to mesenchymal transition in epithelial cells, the phosphatidyl inositol 3 (PI3) kinase/ Akt cellular signaling pathway, telomerase activity and/or expression, tumor metastasis, tumorigenesis, cathepsins, cell senescence, receptor tyrosine kinase signaling, metabolism and drug metabolism, G protein signaling, growth factors and receptors, heat shock proteins, histone deacetylases, hormone receptors, hypoxia, poly ADP-ribose polymerases, protein kinases, RAS signaling, topi
  • the polynucleotides, oncology-related primary constructs and/or oncology-related mmRNA may used to express a polypeptide in cells or tissues for the purpose of replacing the protein produced from a deleted or mutated gene.
  • the oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the invention may be used to treat cancer which has been caused by carcinogens of natural and/or synthetic origin.
  • the use of the oncology-related polynucleotides, oncology-related primary constructs and/or oncology-related mmRNA may be used to treat cancer caused by other organisms and/or cancers caused by viral infection.
  • Flanking Regions Untranslated Regions (UTRs)
  • Untranslated regions (UTRs) of a gene are transcribed but not translated.
  • the 5'UTR starts at the transcription start site and continues to the start codon but does not include the start codon; whereas, the 3'UTR starts immediately following the stop codon and continues until the transcriptional termination signal.
  • the regulatory features of a UTR can be incorporated into the oncology-related polynucleotides, oncology -related primary constructs and/or oncology-related mmRNA of the present invention to enhance the stability of the molecule.
  • the specific features can also be incorporated to ensure controlled down-regulation of the transcript in case they are misdirected to undesired organs sites.
  • Natural 5'UTRs bear features which play roles in for translation initiation. They harbor signatures like Kozak sequences which are commonly known to be involved in the process by which the ribosome initiates translation of many genes. Kozak sequences have the consensus CCR(A/G)CCAUGG, where R is a purine (adenine or guanine) three bases upstream of the start codon (AUG), which is followed by another 'G'. 5'UTR also have been known to form secondary structures which are involved in elongation factor binding.
  • liver-expressed mRNA such as albumin, serum amyloid A, Apolipoprotein A/B/E, transferrin, alpha fetoprotein, erythropoietin, or Factor VIII
  • introduction of 5' UTR of liver-expressed mRNA such as albumin, serum amyloid A, Apolipoprotein A/B/E, transferrin, alpha fetoprotein, erythropoietin, or Factor VIII, could be used to enhance expression of a nucleic acid molecule, such as a mmRNA, in hepatic cell lines or liver.
  • tissue-specific mRNA to improve expression in that tissue is possible - for muscle (MyoD, Myosin, Myoglobin, Myogenin, Herculin), for endothelial cells (Tie-1, CD36), for myeloid cells (C/EBP, AML1, G-CSF, GM-CSF, CD1 lb, MSR, Fr-1, i-NOS), for leukocytes (CD45, CD18), for adipose tissue (CD36, GLUT4, ACRP30, adiponectin) and for lung epithelial cells (SP-A/B/C/D).
  • non-UTR sequences may be incorporated into the 5' (or 3' UTR) UTRs.
  • introns or portions of introns sequences may be incorporated into the flanking regions of the oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the invention. Incorporation of intronic sequences may increase protein production as well as mRNA levels.
  • AU rich elements can be separated into three classes (Chen et al, 1995): Class I AREs contain several dispersed copies of an AUUUA motif within U-rich regions. C-Myc and MyoD contain class I AREs. Class II AREs possess two or more overlapping classes (Chen et al, 1995): Class I AREs contain several dispersed copies of an AUUUA motif within U-rich regions. C-Myc and MyoD contain class I AREs. Class II AREs possess two or more overlapping
  • AREs containing this type of AREs include GM-CSF and TNF-a. Class III ARES are less well defined. These U rich regions do not contain an AUUUA motif. c-Jun and Myogenin are two well-studied examples of this class. Most proteins binding to the AREs are known to destabilize the messenger, whereas members of the ELAV family, most notably HuR, have been documented to increase the stability of mRNA. HuR binds to AREs of all the three classes. Engineering the HuR specific binding sites into the 3' UTR of nucleic acid molecules will lead to HuR binding and thus, stabilization of the message in vivo.
  • AREs 3' UTR AU rich elements
  • oncology-related polynucleotides, oncology- related primary constructs or oncology-related mmRNA of the invention can be used to modulate the stability of oncology-related polynucleotides, oncology- related primary constructs or oncology-related mmRNA of the invention.
  • AREs 3' UTR AU rich elements
  • one or more copies of an ARE can be introduced to make oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the invention less stable and thereby curtail translation and decrease production of the resultant protein.
  • AREs can be identified and removed or mutated to increase the intracellular stability and thus increase translation and production of the resultant protein.
  • Transfection experiments can be conducted in relevant cell lines, using oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the invention and protein production can be assayed at various time points post-transfection.
  • cells can be transfected with different ARE-engineering molecules and by using an ELISA kit to the relevant protein and assaying protein produced at 6 hour, 12 hour, 24 hour, 48 hour, and 7 days post-transfection.
  • microRNAs are 19-25 nucleotide long noncoding RNAs that bind to the 3'UTR of nucleic acid molecules and down-regulate gene expression either by reducing nucleic acid molecule stability or by inhibiting translation.
  • the oncology- related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the invention may comprise one or more microRNA target sequences, microRNA seqences, or microRNA seeds. Such sequences may correspond to any known microRNA such as those taught in US Publication US2005/0261218 and US Publication US2005/0059005, the contents of which are incorporated herein by reference in their entirety.
  • a microRNA sequence comprises a "seed" region, i.e., a sequence in the region of positions 2-8 of the mature microRNA, which sequence has perfect Watson- Crick complementarity to the miRNA target sequence.
  • a microRNA seed may comprise positions 2-8 or 2-7 of the mature microRNA.
  • a microRNA seed may comprise 7 nucleotides (e.g., nucleotides 2-8 of the mature microRNA), wherein the seed-complementary site in the corresponding miRNA target is flanked by an adenine (A) opposed to microRNA position 1.
  • a microRNA seed may comprise 6 nucleotides (e.g., nucleotides 2-7 of the mature microRNA), wherein the seed-complementary site in the corresponding miRNA target is flanked byan adenine (A) opposed to microRNA position 1.
  • A an adenine
  • the bases of the microRNA seed have complete complementarity with the target sequence.
  • microRNA target sequences By engineering microRNA target sequences into the 3'UTR of oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the invention one can target the molecule for degradation or reduced translation, provided the microRNA in question is available. This process will reduce the hazard of off target effects upon nucleic acid molecule delivery. Identification of microRNA, microRNA target regions, and their expression patterns and role in biology have been reported (Bonauer et al, Curr Drug Targets 2010 11 :943-949; Anand and Cheresh Curr Opin Hematol 2011 18: 171-176; Contreras and Rao Leukemia 2012 26:404-413 (2011 Dec 20. doi:
  • miR-122 a microRNA abundant in liver, can inhibit the expression of the gene of interest if one or multiple target sites of miR-122 are engineered into the 3'UTR of the oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA.
  • Introduction of one or multiple binding sites for different microRNA can be engineered to further decrease the longevity, stability, and protein translation of oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA.
  • the term "microRNA site” refers to a microRNA target site or a microRNA recognition site, or any nucleotide sequence to which a microRNA binds or associates. It should be understood that
  • binding may follow traditional Watson-Crick hybridization rules or may reflect any stable association of the microRNA with the target sequence at or adjacent to the microRNA site.
  • microRNA binding sites can be engineered out of (i.e. removed from) sequences in which they naturally occur in order to increase protein expression in specific tissues.
  • miR-122 binding sites may be removed to improve protein expression in the liver. Regulation of expression in multiple tissues can be accomplished through introduction or removal or one or several microRNA binding sites.
  • tissues where microRNA are known to regulate mRNA, and thereby protein expression include, but are not limited to, liver (miR-122), muscle (miR- 133, miPv-206, miR-208), endothelial cells (miR-17-92, miR-126), myeloid cells (miR- 142-3p, miR-142-5p, miR-16, miR-21, miR-223, miR-24, miR-27), adipose tissue (let-7, miR-30c), heart (miR-ld, miR-149), kidney (miR-192, miR-194, miR-204), and lung epithelial cells (let-7, miR-133, miR-126).
  • liver miR-122
  • muscle miR- 133, miPv-206, miR-208
  • endothelial cells miR-17-92, miR-126
  • myeloid cells miR- 142-3p, miR-142-5p, miR-16, miR-21
  • MicroRNA can also regulate complex biological processes such as angiogenesis (miR-132) (Anand and Cheresh Curr Opin Hematol 2011 18: 171-176; herein incorporated by reference in its entirety).
  • angiogenesis miR-132
  • binding sites for microRNAs that are involved in such processes may be removed or introduced, in order to tailor the expression of the oncology-related polynucleotides, oncology-related primary constructs or oncology- related mmRNA expression to biologically relevant cell types or to the context of relevant biological processes.
  • a listing of MicroRNA, miR sequences and miR binding sites is listed in Table 9 of U.S.
  • Provisional Application No. 61/753,661 filed January 17, 2013, in Table 9 of U.S. Provisional Application No. 61/754,159 filed January 18, 2013, and in Table 7 of U.S. Provisional Application No. 61/758,921 filed January 31, 2013, each of which are herein incorporated by reference in their entireties.
  • oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA can be engineered for more targeted expression in specific cell types or only under specific biological conditions.
  • polynucleotides, oncology-related primary constructs or oncology-related mmRNA could be designed that would be optimal for oncology-related protein expression in a tissue or in the context of a biological condition.
  • microRNA seed sites can be incorporated into mRNA to decrease expression in certain cells which results in a biological improvement.
  • An example of this is incorporation of miR- 142 sites into a UGT1A1 -expressing lentiviral vector.
  • hematopoietic cells could also reduce or abolish immune responses to the mRNA- encoded protein.
  • Incorporation of miR-142 seed sites (one or multiple) into mRNA would be important in the case of treatment of patients with complete protein deficiencies such as, but not limited to, UGTl Al type I, LDLR-deficient patients abd CRIM-negative Pompe patients.
  • Transfection experiments can be conducted in relevant cell lines, using engineered oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA and protein production can be assayed at various time points post-transfection.
  • cells can be transfected with different microRNA binding site-engineering oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA and by using an ELISA kit to the relevant protein and assaying protein produced at 6 hour, 12 hour, 24 hour, 48 hour, 72 hour and 7 days post-transfection.
  • In vivo experiments can also be conducted using microRNA- binding site-engineered molecules to examine changes in tissue-specific expression of formulated oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA.
  • the 5' cap structure of an mRNA is involved in nuclear export, increasing mRNA stability and binds the mRNA Cap Binding Protein (CBP), which is responsibile for mRNA stability in the cell and translation competency through the association of CBP with poly(A) binding protein to form the mature cyclic mRNA species.
  • CBP mRNA Cap Binding Protein
  • the cap further assists the removal of 5' proximal introns removal during mRNA splicing.
  • Endogenous mRNA molecules may be 5 '-end capped generating a 5'-ppp-5'- triphosphate linkage between a terminal guanosine cap residue and the 5 '-terminal transcribed sense nucleotide of the mRNA molecule.
  • This 5'-guanylate cap may then be methylated to generate an N7-methyl-guanylate residue.
  • the ribose sugars of the terminal and/or anteterminal transcribed nucleotides of the 5' end of the mRNA may optionally also be 2'-0-methylated.
  • 5'-decapping through hydrolysis and cleavage of the guanylate cap structure may target a nucleic acid molecule, such as an mRNA molecule, for degradation.
  • Modifications to the oncology-related polynucleotides, oncology-related primary constructs, and oncology-related mmRNA of the present invention may generate a non-hydrolyzable cap structure preventing decapping and thus increasing mRNA half- life.
  • modified nucleotides may be used during the capping reaction.
  • a Vaccinia Capping Enzyme from New England Biolabs (Ipswich, MA) may be used with a-thio-guanosine nucleotides according to the manufacturer's instructions to create a phosphorothioate linkage in the 5'-ppp-5' cap.
  • Additional modified guanosine nucleotides may be used such as a-methyl-phosphonate and seleno-phosphate nucleotides.
  • Additional modifications include, but are not limited to, 2'-0-methylation of the ribose sugars of 5 '-terminal and/or 5'-anteterminal nucleotides of the mRNA (as mentioned above) on the 2'-hydroxyl group of the sugar ring.
  • Multiple distinct 5 '-cap structures can be used to generate the 5 '-cap of a nucleic acid molecule, such as an mRNA molecule.
  • Cap analogs which herein are also referred to as synthetic cap analogs, chemical caps, chemical cap analogs, or structural or functional cap analogs, differ from natural (i.e. endogenous, wild-type or physiological) 5'-caps in their chemical structure, while retaining cap function. Cap analogs may be chemically (i.e. non-enzymatically) or enzymatically synthesized and/or linked to a nucleic acid molecule.
  • the Anti-Reverse Cap Analog (ARCA) cap contains two guanines linked by a 5 '-5 '-triphosphate group, wherein one guanine contains an N7 methyl group as well as a 3'-0-methyl group (i.e., N7,3'-0-dimethyl-guanosine-5'- triphosphate-5 '-guanosine (m 7 G-3'mppp-G; which may equivaliently be designated 3' O- Me-m7G(5')ppp(5')G).
  • the 3'-0 atom of the other, unmodified, guanine becomes linked to the 5'-terminal nucleotide of the capped nucleic acid molecule (e.g.
  • mRNA or mmRNA an mRNA or mmRNA
  • the N7- and 3'-0-methlyated guanine provides the terminal moiety of the capped nucleic acid molecule (e.g. mRNA or mmRNA).
  • mCAP is Another exemplary cap, which is similar to ARCA but has a 2'-0- methyl group on guanosine (i.e., N7,2'-0-dimethyl-guanosine-5'-triphosphate-5'- guanosine, m 7 Gm-ppp-G).
  • cap analogs allow for the concomitant capping of a nucleic acid molecule in an in vitro transcription reaction, up to 20% of transcripts can remain uncapped. This, as well as the structural differences of a cap analog from an endogenous 5 '-cap structures of nucleic acids produced by the endogenous, cellular transcription machinery, may lead to reduced translational competency and reduced cellular stability.
  • Oncology-related polynucleotides, oncology-related primary constructs and oncology-related mmRNA of the invention may also be capped post-transcriptionally, using enzymes, in order to generate more authentic 5 '-cap structures.
  • the phrase "more authentic” refers to a feature that closely mirrors or mimics, either structurally or functionally, an endogenous or wild type feature. That is, a "more authentic" feature is better representative of an endogenous, wild-type, natural or physiological cellular function and/or structure as compared to synthetic features or analogs, etc., of the prior art, or which outperforms the corresponding endogenous, wild- type, natural or physiological feature in one or more respects.
  • Non-limiting examples of more authentic 5 'cap structures of the present invention are those which, among other things, have enhanced binding of cap binding proteins, increased half life, reduced susceptibility to 5' endonucleases and/or reduced 5'decapping, as compared to synthetic 5 'cap structures known in the art (or to a wild-type, natural or physiological 5 'cap structure).
  • recombinant Vaccinia Virus Capping Enzyme and recombinant 2'-0-methyltransferase enzyme can create a canonical 5 '-5 '-triphosphate linkage between the 5 '-terminal nucleotide of an mRNA and a guanine cap nucleotide wherein the cap guanine contains an N7 methylation and the 5 '-terminal nucleotide of the mRNA contains a 2'-0-methyl.
  • Capl structure Such a structure is termed the Capl structure.
  • Cap structures include, but are not limited to, 7mG(5')ppp(5')N,pN2p (cap 0), 7mG(5')ppp(5')NlmpNp (cap 1), and 7mG(5')-ppp(5')NlmpN2mp (cap 2).
  • Cap structures include, but are not limited to, 7mG(5')ppp(5')N,pN2p (cap 0), 7mG(5')ppp(5')NlmpNp (cap 1), and 7mG(5')-ppp(5')NlmpN2mp (cap 2).
  • polynucleotides, oncology-related primary constructs or oncology-related mmRNA may be capped. This is in contrast to -80% when a cap analog is linked to an mRNA in the course of an in vitro transcription reaction.
  • 5' terminal caps may include endogenous caps or cap analogs.
  • a 5' terminal cap may comprise a guanine analog.
  • Useful guanine analogs include, but are not limited to, inosine, Nl- methyl-guanosine, 2'fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino- guanosine, LNA-guanosine, and 2-azido-guanosine.
  • Additional viral sequences such as, but not limited to, the translation enhancer sequence of the barley yellow dwarf virus (BYDV-PAV) , the Jaagsiekte sheep retrovirus (JSRV) and/or the Enzootic nasal tumor virus (See e.g., International Pub. No.
  • WO2012129648 can be engineered and inserted in the 3' UTR of the oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the invention and can stimulate the translation of the construct in vitro and in vivo.
  • Transfection experiments can be conducted in relevant cell lines at and protein production can be assayed by ELISA at 12hr, 24hr, 48hr, 72 hr and day 7 post-transfection.
  • oncology-related polynucleotides oncology-related primary constructs or oncology-related mmRNA which may contain an internal ribosome entry site (IRES).
  • IRES internal ribosome entry site
  • Picorna virus RNA IRES plays an important role in initiating protein synthesis in absence of the 5' cap structure.
  • An IRES may act as the sole ribosome binding site, or may serve as one of multiple ribosome binding sites of an mRNA.
  • Oncology-related polynucleotides oncology-related primary constructs or oncology-related mmRNA containing more than one functional ribosome binding site may encode several oncology-related peptides or oncology-related polypeptides that are translated independently by the ribosomes ("multicistronic nucleic acid molecules").
  • oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA are provided with an IRES, further optionally provided is a second translatable region.
  • IRES sequences that can be used according to the invention include without limitation, those from picornaviruses (e.g. FMDV), pest viruses (CFFV), polio viruses (PV), encephalomyocarditis viruses
  • ECMV foot-and-mouth disease viruses
  • FMDV foot-and-mouth disease viruses
  • HCV hepatitis C viruses
  • CSFV classical swine fever viruses
  • MLV murine leukemia virus
  • SIV simian immune deficiency viruses
  • CrPV cricket paralysis viruses
  • a long chain of adenine nucleotides may be added to a polynucleotide such as an mRNA molecule in order to increase stability.
  • a polynucleotide such as an mRNA molecule
  • the 3' end of the transcript may be cleaved to free a 3' hydroxyl.
  • poly-A polymerase adds a chain of adenine nucleotides to the RNA.
  • the process called polyadenylation, adds a poly-A tail that can be between ,for example, approximately 100 and 250 residues long.
  • the length of a poly-A tail of the present invention is greater than 30 nucleotides in length.
  • the poly-A tail is greater than 35 nucleotides in length (e.g., at least or greater than about 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, and 3,000 nucleotides).
  • the oncology-related polynucleotide, oncology- related primary construct, or oncology-related mmRNA includes from about 30 to about 3,000 nucleotides (e.g., from 30 to 50, from 30 to 100, from 30 to 250, from 30 to 500, from 30 to 750, from 30 to 1,000, from 30 to 1,500, from 30 to 2,000, from 30 to 2,500, from 50 to 100, from 50 to 250, from 50 to 500, from 50 to 750, from 50 to 1,000, from 50 to 1,500, from 50 to 2,000, from 50 to 2,500, from 50 to 3,000, from 100 to 500, from 100 to 750, from 100 to 1,000, from 100 to 1,500, from 100 to 2,000, from 100 to 2,500, from 100 to 3,000, from 500 to 750, from 500 to 1,000, from 500 to 1,500, from 500 to 2,000, from 500 to 2,500, from 500 to 3,000, from 1,000 to 1,500, from 1,000 to 2,000, from 1,000 to 2,500, from 1,000 to 3,000, from 1,500, from 1,000
  • the poly-A tail is designed relative to the length of the overall oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA. This design may be based on the length of the coding region, the length of a particular feature or region (such as the first or flanking regions), or based on the length of the ultimate product expressed from the oncology-related
  • polynucleotides oncology-related primary constructs or oncology-related mmRNA.
  • the poly-A tail may be 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100% greater in length than the oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA or feature thereof.
  • the poly-A tail may also be designed as a fraction of oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA to which it belongs.
  • the poly-A tail may be 10, 20, 30, 40, 50, 60, 70, 80, or 90% or more of the total length of the construct or the total length of the construct minus the poly-A tail.
  • engineered binding sites and conjugation of oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA for Poly-A binding protein may enhance expression.
  • oncology-related polynucleotides, oncology- related primary constructs or oncology-related mmRNA may be linked together to the PABP (Poly-A binding protein) through the 3 '-end using modified nucleotides at the 3'- terminus of the poly-A tail.
  • Transfection experiments can be conducted in relevant cell lines and oncology-related protein production can be assayed by ELISA at 12hr, 24hr, 48hr, 72 hr and day 7 post-transfection.
  • the oncology-related polynucleotide and oncology-related primary constructs of the present invention are designed to include a polyA-G quartet.
  • the G-quartet is a cyclic hydrogen bonded array of four guanine nucleotides that can be formed by G-rich sequences in both DNA and RNA.
  • the G-quartet is incorporated at the end of the poly-A tail.
  • the resultant oncology-related mmRNA construct is assayed for stability, protein production and other parameters including half- life at various time points. It has been discovered that the polyA-G quartet results in protein production equivalent to at least 75% of that seen using a poly-A tail of 120 nucleotides alone.
  • the oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA of the present invention may be quantified in exosomes derived from one or more bodily fluid.
  • bodily fluids include peripheral blood, serum, plasma, ascites, urine, cerebrospinal fluid (CSF), sputum, saliva, bone marrow, synovial fluid, aqueous humor, amniotic fluid, cerumen, breast milk, broncheoalveolar lavage fluid, semen, prostatic fluid, cowper's fluid or pre- ejaculatory fluid, sweat, fecal matter, hair, tears, cyst fluid, pleural and peritoneal fluid, pericardial fluid, lymph, chyme, chyle, bile, interstitial fluid, menses, pus, sebum, vomit, vaginal secretions, mucosal secretion, stool water, pancreatic juice, lavage fluids from peripheral blood, serum, plasma, ascites, urine
  • exosomes may be retrieved from an organ selected from the group consisting of lung, heart, pancreas, stomach, intestine, bladder, kidney, ovary, testis, skin, colon, breast, prostate, brain, esophagus, liver, and placenta.
  • a sample of not more than 2mL is obtained from the subject and the exosomes isolated by size exclusion chromatography, density gradient centrifugation, differential centrifugation, nanomembrane ultrafiltration,
  • the level or concentration of an oncology-related polynucleotide, oncology-related primary construct or oncology-related mmRNA may be an expression level, presence, absence, truncation or alteration of the administered construct. It is advantageous to correlate the level with one or more clinical phenotypes or with an assay for a human disease biomarker.
  • the assay may be performed using construct specific probes, cytometry, qRT-PCR, real-time PCR, PCR, flow cytometry, electrophoresis, mass spectrometry, or combinations thereof while the exosomes may be isolated using immunohistochemical methods such as enzyme linked immunosorbent assay (ELISA) methods. Exosomes may also be isolated by size exclusion chromatography, density gradient centrifugation, differential centrifugation, nanomembrane ultrafiltration, immunoabsorbent capture, affinity purification, microfluidic separation, or combinations thereof.
  • immunohistochemical methods such as enzyme linked immunosorbent assay (ELISA) methods.
  • Exosomes may also be isolated by size exclusion chromatography, density gradient centrifugation, differential centrifugation, nanomembrane ultrafiltration, immunoabsorbent capture, affinity purification, microfluidic separation, or combinations thereof.
  • Oncology-related polynucleotides, oncology-related primary constructs or oncology-related mmRNA for use in accordance with the invention may be prepared according to any available technique including, but not limited to chemical synthesis, enzymatic synthesis, which is generally termed in vitro transcription (IVT) or enzymatic or chemical cleavage of a longer precursor, etc.
  • IVT in vitro transcription
  • Methods of synthesizing RNAs are known in the art (see, e.g., Gait, M.J. (ed.) Oligonucleotide synthesis: a practical approach, Oxford [Oxfordshire], Washington, DC: IRL Press, 1984; and Herdewijn, P.
  • the process of design and synthesis of the oncology-related primary constructs of the invention generally includes the steps of gene construction, mRNA production (either with or without modifications) and purification.
  • a target oncology-related polynucleotide sequence encoding the oncology-related polypeptide of interest is first selected for incorporation into a vector which will be amplified to produce a cDNA template.
  • the target oncology- related polynucleotide sequence and/or any flanking sequences may be codon optimized.
  • the cDNA template is then used to produce mRNA through in vitro transcription (IVT). After production, the mRNA may undergo purification and clean-up processes. The steps of which are provided in more detail below.
  • the step of gene construction may include, but is not limited to gene synthesis, vector amplification, plasmid purification, plasmid linearization and clean-up, and cDNA template synthesis and clean-up.
  • an oncology-related primary construct is designed.
  • a first region of linked nucleosides encoding the polypeptide of interest may be constructed using an open reading frame (ORF) of a selected nucleic acid (DNA or RNA) transcript.
  • the ORF may comprise the wild type ORF, an isoform, variant or a fragment thereof.
  • an "open reading frame” or “ORF” is meant to refer to a nucleic acid sequence (DNA or RNA) which is capable of encoding an oncology-related polypeptide of interest. ORFs often begin with the start codon, ATG and end with a nonsense or termination codon or signal.
  • the nucleotide sequence of the first region may be codon optimized. Codon optimization methods are known in the art and may be useful in efforts to achieve one or more of several goals. These goals include to match codon frequencies in target and host organisms to ensure proper folding, bias GC content to increase mRNA stability or reduce secondary structures, minimize tandem repeat codons or base runs that may impair gene construction or expression, customize transcriptional and translational control regions, insert or remove protein trafficking sequences, remove/add post translation modification sites in encoded protein (e.g.
  • Codon optimization tools, algorithms and services are known in the art, non- limiting examples include services from GeneArt (Life Technologies), DNA2.0 (Menlo Park CA) and/or proprietary methods.
  • the ORF sequence is optimized using optimization algorithms. Codon options for each amino acid are given in Table 1.
  • flanking regions may be incorporated into the oncology-related primary construct before and/or after optimization of the ORF. It is not required that an oncology-related primary construct contain both a 5' and 3' flanking region. Examples of such features include, but are not limited to, untranslated regions (UTRs), Kozak sequences, an oligo(dT) sequence, and detectable tags and may include multiple cloning sites which may have Xbal recognition.
  • a 5' UTR and/or a 3' UTR may be provided as flanking regions. Multiple 5 ' or 3' UTRs may be included in the flanking regions and may be the same or of different sequences. Any portion of the flanking regions, including none, may be codon optimized and any may independently contain one or more different structural or chemical modifications, before and/or after codon optimization. Combinations of features may be included in the first and second flanking regions and may be contained within other features.
  • the ORF may be flanked by a 5' UTR which may contain a strong Kozak translational initiation signal and/or a 3' UTR which may include an oligo(dT) sequence for templated addition of a poly-A tail.
  • the 5'UTR may comprise a first polynucleotide fragment and a second polynucleotide fragment from the same and/or different genes such as the 5 'UTRs described in US Patent Application
  • Tables 2 and 3 provide a listing of exemplary UTRs which may be utilized in the oncology-related primary construct of the present invention as flanking regions. Shown in Table 2 is a listing of a 5 '-untranslated region of the invention. Variants of 5' UTRs may be utilized wherein one or more nucleotides are added or removed to the termini, including A, T, C or G.
  • Table 3 Shown in Table 3 is a representative listing of 3 '-untranslated regions of the invention. Variants of 3 ' UTRs may be utilized wherein one or more nucleotides are added or removed to the termini, including A, T, C or G.
  • any UTR from any gene may be incorporated into the respective first or second flanking region of the primary construct.
  • multiple wild-type UTRs of any known gene may be utilized. It is also within the scope of the present invention to provide artificial UTRs which are not variants of wild type genes. These UTRs or portions thereof may be placed in the same orientation as in the transcript from which they were selected or may be altered in orientation or location. Hence a 5 ' or 3' UTR may be inverted, shortened, lengthened, made chimeric with one or more other 5' UTRs or 3' UTRs.
  • the term "altered" as it relates to a UTR sequence means that the UTR has been changed in some way in relation to a reference sequence.
  • a 3' or 5' UTR may be altered relative to a wild type or native UTR by the change in orientation or location as taught above or may be altered by the inclusion of additional nucleotides, deletion of nucleotides, swapping or transposition of nucleotides. Any of these changes producing an "altered" UTR (whether 3 Or 5') comprise a variant UTR.
  • a double, triple or quadruple UTR such as a 5' or 3' UTR may be used.
  • a "double" UTR is one in which two copies of the same UTR are encoded either in series or substantially in series.
  • a double beta- globin 3' UTR may be used as described in US Patent publication 20100129877, the contents of which are incorporated herein by reference in its entirety.
  • patterned UTRs are those UTRs which reflect a repeating or alternating pattern, such as ABABAB or AABBAABBAABB or ABCABCABC or variants thereof repeated once, twice, or more than 3 times. In these patterns, each letter, A, B, or C represent a different UTR at the nucleotide level.
  • flanking regions are selected from a family of transcripts whose proteins share a common function, structure, feature of property.
  • oncology-related polypeptides of interest may belong to a family of proteins which are expressed in a particular cell, tissue or at some time during development.
  • the UTRs from any of these genes may be swapped for any other UTR of the same or different family of proteins to create a new chimeric primary transcript.
  • a "family of proteins" is used in the broadest sense to refer to a group of two or more oncology-related polypeptides of interest which share at least one function, structure, feature, localization, origin, or expression pattern.
  • the oncology-related primary construct components are reconstituted and transformed into a vector such as, but not limited to, plasmids, viruses, cosmids, and artificial chromosomes.
  • a vector such as, but not limited to, plasmids, viruses, cosmids, and artificial chromosomes.
  • the optimized construct may be reconstituted and transformed into chemically competent E. coli, yeast, neurospora, maize, drosophila, etc. where high copy plasmid-like or chromosome structures occur by methods described herein.
  • the untranslated region may also include translation enhancer elements (TEE).
  • TEE translation enhancer elements
  • the TEE may include those described in US Application No. 20090226470, herein incorporated by reference in its entirety, and those known in the art.
  • the oncology-related primary constructs of the present invention may include at least two stop codons before the 3' untranslated region (UTR).
  • the stop codon may be selected from TGA, TAA and TAG.
  • the oncology-related primary constructs of the present invention include the stop codon TGA and one additional stop codon.
  • the addition stop codon may be TAA.
  • the primary constructs of the present invention include three stop codons.
  • the vector containing the oncology-related primary construct is then amplified and the plasmid isolated and purified using methods known in the art such as, but not limited to, a maxi prep using the Invitrogen PURELINKTM HiPure Maxiprep Kit (Carlsbad, CA).
  • the plasmid may then be linearized using methods known in the art such as, but not limited to, the use of restriction enzymes and buffers.
  • the linearization reaction may be purified using methods including, for example Invitrogen's PURELINKTM PCR Micro Kit (Carlsbad, CA), and HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP- HPLC), and hydrophobic interaction HPLC (HIC-HPLC) and Invitrogen's standard PURELINKTM PCR Kit (Carlsbad, CA).
  • the purification method may be modified depending on the size of the linearization reaction which was conducted.
  • the linearized plasmid is then used to generate cDNA for in vitro transcription (IVT) reactions.
  • a cDNA template may be synthesized by having a linearized plasmid undergo polymerase chain reaction (PCR).
  • Table 4 is a listing of primers and probes that may be useful in the PCR reactions of the present invention. It should be understood that the listing is not exhaustive and that primer-probe design for any amplification is within the skill of those in the art. Probes may also contain chemically modified bases to increase base-pairing fidelity to the target molecule and base-pairing strength. Such modifications may include 5-methyl-Cytidine, 2, 6-di-amino-purine, 2'-fluoro, phosphoro-thioate, or locked nucleic acids.
  • URP universal reverse primer
  • the cDNA may be submitted for sequencing analysis before undergoing transcription.
  • the process of mRNA or mmRNA production may include, but is not limited to, in vitro transcription, cDNA template removal and RNA clean-up, and mRNA capping and/or tailing reactions.
  • the cDNA produced in the previous step may be transcribed using an in vitro transcription (IVT) system.
  • the system typically comprises a transcription buffer, nucleotide triphosphates (NTPs), an RNase inhibitor and a polymerase.
  • NTPs may be manufactured in house, may be selected from a supplier, or may be synthesized as described herein.
  • the NTPs may be selected from, but are not limited to, those described herein including natural and unnatural (modified) NTPs.
  • the polymerase may be selected from, but is not limited to, T7 RNA polymerase, T3 RNA polymerase and mutant polymerases such as, but not limited to, polymerases able to be incorporated into modified nucleic acids.
  • RNA polymerases or variants may be used in the design of the oncology-related primary constructs of the present invention.
  • RNA polymerases may be modified by inserting or deleting amino acids of the RNA polymerase sequence.
  • the RNA polymerase may be modified to exhibit an increased ability to incorporate a 2 '-modified nucleotide triphosphate compared to an unmodified RNA polymerase (see International Publication WO2008078180 and U.S. Patent 8,101,385; herein incorporated by reference in their entireties).
  • Variants may be obtained by evolving an RNA polymerase, optimizing the RNA polymerase amino acid and/or nucleic acid sequence and/or by using other methods known in the art.
  • T7 RNA polymerase variants may be evolved using the continuous directed evolution system set out by Esvelt et al.
  • T7 RNA polymerase may encode at least one mutation such as, but not limited to, lysine at position 93 substituted for threonine (K93T), I4M, A7T, E63V, V64D, A65E, D66Y, T76N, C125R, S128R, A136T, N165S, G175R, H176L, Y178H, F182L, L196F, G198V, D208Y, E222K, S228A, Q239R, T243N, G259D, M267I, G280C, H300R, D351A, A354S, E356D, L360P, A383V, Y385C, D388Y, S397R, M401T, N410S, K450R, P451T, G452V, E484A, H5
  • T7 RNA polymerase variants may encode at least mutation as described in U.S. Pub. Nos. 20100120024 and 20070117112; herein incorporated by reference in their entireties.
  • Variants of RNA polymerase may also include, but are not limited to, substitutional variants, conservative amino acid substitution, insertional variants, deletional variants and/or covalent derivatives.
  • the oncology-related primary construct may be designed to be recognized by the wild type or variant R A polymerases. In doing so, the oncology-related primary construct may be modified to contain sites or regions of sequence changes from the wild type or parent primary construct.
  • the oncology-related primary construct may be designed to include at least one substitution and/or insertion upstream of an RNA polymerase binding or recognition site, downstream of the RNA polymerase binding or recognition site, upstream of the TATA box sequence, downstream of the TATA box sequence of the oncology-related primary construct but upstream of the coding region of the oncology- related primary construct, within the 5'UTR, before the 5'UTR and/or after the 5'UTR.
  • the 5 'UTR of the oncology-related primary construct may be replaced by the insertion of at least one region and/or string of nucleotides of the same base.
  • the region and/or string of nucleotides may include, but is not limited to, at least 3, at least 4, at least 5, at least 6, at least 7 or at least 8 nucleotides and the nucleotides may be natural and/or unnatural.
  • the group of nucleotides may include 5-8 adenine, cytosine, thymine, a string of any of the other nucleotides disclosed herein and/or combinations thereof.
  • the 5 'UTR of the oncology-related primary construct may be replaced by the insertion of at least two regions and/or strings of nucleotides of two different bases such as, but not limited to, adenine, cytosine, thymine, any of the other nucleotides disclosed herein and/or combinations thereof.
  • the 5'UTR may be replaced by inserting 5-8 adenine bases followed by the insertion of 5-8 cytosine bases.
  • the 5'UTR may be replaced by inserting 5-8 cytosine bases followed by the insertion of 5-8 adenine bases.
  • the oncology-related primary construct may include at least one substitution and/or insertion downstream of the transcription start site which may be recognized by an RNA polymerase.
  • at least one substitution and/or insertion may occur downstream the transcription start site by substituting at least one nucleic acid in the region just downstream of the transcription start site (such as, but not limited to, +1 to +6).
  • NTP nucleotide triphosphate
  • the oncology-related primary construct may include the substitution of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12 or at least 13 guanine bases downstream of the transcription start site.
  • the oncology-related primary construct may include the substitution of at least 1, at least 2, at least 3, at least 4, at least 5 or at least 6 guanine bases in the region just downstream of the transcription start site.
  • the guanine bases may be substituted by at least 1, at least 2, at least 3 or at least 4 adenine nucleotides.
  • the nucleotides in the region are GGGAGA the guanine bases may be substituted by at least 1, at least 2, at least 3 or at least 4 cytosine bases.
  • the guanine bases in the region are GGGAGA the guanine bases may be substituted by at least 1, at least 2, at least 3 or at least 4 thymine, and/or any of the nucleotides described herein.
  • the oncology-related primary construct may include at least one substitution and/or insertion upstream of the start codon.
  • start codon is the first codon of the protein coding region whereas the transcription start site is the site where transcription begins.
  • the oncology-related primary construct may include, but is not limited to, at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7 or at least 8 substitutions and/or insertions of nucleotide bases.
  • the nucleotide bases may be inserted or substituted at 1, at least 1, at least 2, at least 3, at least 4 or at least 5 locations upstream of the start codon.
  • the nucleotides inserted and/or substituted may be the same base (e.g., all A or all C or all T or all G), two different bases (e.g., A and C, A and T, or C and T), three different bases (e.g., A, C and T or A, C and T) or at least four different bases.
  • the guanine base upstream of the coding region in the oncology-related primary construct may be substituted with adenine, cytosine, thymine, or any of the nucleotides described herein.
  • the substitution of guanine bases in the oncology-related primary construct may be designed so as to leave one guanine base in the region downstream of the transcription start site and before the start codon (see Esvelt et al. Nature (2011) 472(7344):499-503; herein incorporated by reference in its entirety).
  • at least 5 nucleotides may be inserted at 1 location downstream of the transcription start site but upstream of the start codon and the at least 5 nucleotides may be the same base type.
  • RNA clean-up may also include a purification method such as, but not limited to, AGENCOURT®
  • CLEANSEQ® system from Beckman Coulter (Danvers, MA), HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC- HPLC) .
  • the oncology-related primary construct or oncology-related mmRNA may also undergo capping and/or tailing reactions.
  • a capping reaction may be performed by methods known in the art to add a 5' cap to the 5' end of the oncology-related primary construct. Methods for capping include, but are not limited to, using a Vaccinia Capping enzyme (New England Biolabs, Ipswich, MA).
  • a poly-A tailing reaction may be performed by methods known in the art, such as, but not limited to, 2' O-methyltransferase and by methods as described herein. If the oncology-related primary construct generated from cDNA does not include a poly-T, it may be beneficial to perform the poly-A-tailing reaction before the oncology-related primary construct is cleaned.
  • Primary construct or mmRNA purification may include, but is not limited to, mRNA or mmRNA clean-up, quality assurance and quality control.
  • mRNA or mmRNA clean-up may be performed by methods known in the arts such as, but not limited to, AGENCOURT® beads (Beckman Coulter Genomics, Danvers, MA), poly-T beads, LNATM oligo-T capture probes (EXIQON® Inc, Vedbaek, Denmark) or HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC-HPLC).
  • AGENCOURT® beads Beckman Coulter Genomics, Danvers, MA
  • poly-T beads poly-T beads
  • LNATM oligo-T capture probes EXIQON® Inc, Vedbaek, Denmark
  • HPLC based purification methods such as, but not limited to, strong anion exchange HPLC
  • purified when used in relation to a polynucleotide such as a “purified mRNA or mmRNA” refers to one that is separated from at least one contaminant.
  • a "contaminant” is any substance which makes another unfit, impure or inferior.
  • a purified oncology-related polynucleotide e.g., DNA and RNA
  • a purified oncology-related polynucleotide e.g., DNA and RNA
  • a quality assurance and/or quality control check may be conducted using methods such as, but not limited to, gel electrophoresis, UV absorbance, or analytical HPLC.
  • the oncology-related mRNA or oncology-related mmRNA may be sequenced by methods including, but not limited to reverse- transcriptase-PCR.
  • the oncology-related mRNA or oncology-related mmRNA may be quantified using methods such as, but not limited to, ultraviolet visible spectroscopy (UV/Vis).
  • UV/Vis ultraviolet visible spectroscopy
  • a non-limiting example of a UV/Vis spectrometer is a UV/Vis spectrometer.
  • the quantified oncology- related mRNA or oncology-related mmRNA may be analyzed in order to determine if the oncology-related mRNA or oncology-related mmRNA may be of proper size, check that no degradation of the oncology-related mRNA or oncology-related mmRNA has occurred.
  • Degradation of the oncology-related mRNA and/or oncology-related mmRNA may be checked by methods such as, but not limited to, agarose gel electrophoresis, HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC-HPLC), liquid chromatography-mass spectrometry (LCMS), capillary electrophoresis (CE) and capillary gel electrophoresis (CGE).
  • agarose gel electrophoresis HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC-HPLC), liquid chromatography-mass spectrometry (LCMS), capillary electrophoresis (CE) and capillary gel electrophoresis (CGE).
  • the oncology-related primary constructs or oncology-related mmR A may also encode additional features which facilitate trafficking of the oncology-related polypeptides to therapeutically relevant sites.
  • One such feature which aids in protein trafficking is the signal sequence.
  • a "signal sequence" or “signal peptide” is a polynucleotide or polypeptide, respectively, which is from about 9 to 200 nucleotides (3-60 amino acids) in length which is incorporated at the 5' (or N-terminus) of the coding region or polypeptide encoded, respectively. Addition of these sequences result in trafficking of the encoded oncology-related polypeptide to the endoplasmic reticulum through one or more secretory pathways. Some signal peptides are cleaved from the protein by signal peptidase after the proteins are transported.

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PCT/US2013/030070 2012-04-02 2013-03-09 Modified polynucleotides for the production of oncology-related proteins and peptides Ceased WO2013151672A2 (en)

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EP13772721.0A EP2833892A4 (en) 2012-04-02 2013-03-09 MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF PROTEINS AND PEPTIDES USEFUL IN ONCOLOGY
CA2868393A CA2868393A1 (en) 2012-04-02 2013-03-09 Modified polynucleotides for the production of oncology-related proteins and peptides
JP2015504571A JP2015518816A (ja) 2012-04-02 2013-03-09 腫瘍学関連タンパク質およびペプチドの産生のための修飾ポリヌクレオチド
HK15107391.3A HK1206636A1 (zh) 2012-04-02 2013-03-09 用於制备肿瘤相关蛋白和多肽的修饰的多核苷酸
AU2013243955A AU2013243955B2 (en) 2012-04-02 2013-03-09 Modified polynucleotides for the production of oncology-related proteins and peptides
CA2868418A CA2868418A1 (en) 2012-04-02 2013-03-15 In vivo production of proteins
JP2015504587A JP6348482B2 (ja) 2012-04-02 2013-03-15 タンパク質のインビボ産生
US14/390,106 US9221891B2 (en) 2012-04-02 2013-03-15 In vivo production of proteins
CN202010645626.3A CN112390871A (zh) 2012-04-02 2013-03-15 蛋白质的体内产生
AU2013243834A AU2013243834A1 (en) 2012-04-02 2013-03-15 In vivo production of proteins
CN201380028186.5A CN104870022B (zh) 2012-04-02 2013-03-15 蛋白质的体内产生
HK15107400.2A HK1206639B (en) 2012-04-02 2013-03-15 In vivo production of proteins
EP13713306.2A EP2833922B1 (en) 2012-04-02 2013-03-15 In vivo production of proteins
EP18204317.4A EP3520820A1 (en) 2012-04-02 2013-03-15 In vivo production of proteins
PCT/US2013/031821 WO2013151736A2 (en) 2012-04-02 2013-03-15 In vivo production of proteins
US14/107,029 US20140113959A1 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding caspase 6
US14/106,988 US9301993B2 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding apoptosis inducing factor 1
US14/107,079 US9149506B2 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding septin-4
US14/107,053 US9216205B2 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding granulysin
US14/107,105 US9255129B2 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding SIAH E3 ubiquitin protein ligase 1
US14/824,247 US9572896B2 (en) 2012-04-02 2015-08-12 In vivo production of proteins
US15/015,684 US9587003B2 (en) 2012-04-02 2016-02-04 Modified polynucleotides for the production of oncology-related proteins and peptides
US15/403,517 US10493167B2 (en) 2012-04-02 2017-01-11 In vivo production of proteins
JP2017012947A JP6953135B6 (ja) 2012-04-02 2017-01-27 タンパク質のインビボ産生
US15/425,813 US10501513B2 (en) 2012-04-02 2017-02-06 Modified polynucleotides for the production of oncology-related proteins and peptides
AU2017232121A AU2017232121B2 (en) 2012-04-02 2017-09-21 In vivo production of proteins
AU2018200377A AU2018200377A1 (en) 2012-04-02 2018-01-19 Modified polynucleotides for the production of oncology-related proteins and peptides
AU2019202835A AU2019202835A1 (en) 2012-04-02 2019-04-23 In vivo production of proteins
US16/442,168 US10583203B2 (en) 2012-04-02 2019-06-14 In vivo production of proteins
US16/707,998 US20200247861A1 (en) 2012-04-02 2019-12-09 Modified polynucleotides for the production of oncology-related proteins and peptides
JP2019225097A JP2020072670A (ja) 2012-04-02 2019-12-13 タンパク質のインビボ産生
US16/811,648 US20210077634A1 (en) 2012-04-02 2020-03-06 In vivo production of proteins
AU2020257150A AU2020257150A1 (en) 2012-04-02 2020-10-23 In vivo production of proteins
JP2022020499A JP2022078081A (ja) 2012-04-02 2022-02-14 タンパク質のインビボ産生
AU2023263451A AU2023263451A1 (en) 2012-04-02 2023-11-07 In vivo production of proteins
JP2024018721A JP2024063025A (ja) 2012-04-02 2024-02-09 タンパク質のインビボ産生
US18/592,122 US20250074962A1 (en) 2012-04-02 2024-02-29 Modified polynucleotides for the production of oncology-related proteins and peptides

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US201261618957P 2012-04-02 2012-04-02
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US14/107,029 Continuation US20140113959A1 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding caspase 6
US14/107,053 Continuation US9216205B2 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding granulysin
US14/107,105 Continuation US9255129B2 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding SIAH E3 ubiquitin protein ligase 1
US14/106,988 Continuation US9301993B2 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding apoptosis inducing factor 1
US14/107,079 Continuation US9149506B2 (en) 2012-04-02 2013-12-16 Modified polynucleotides encoding septin-4

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PCT/US2013/030066 Ceased WO2013151669A1 (en) 2012-04-02 2013-03-09 Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
PCT/US2013/030070 Ceased WO2013151672A2 (en) 2012-04-02 2013-03-09 Modified polynucleotides for the production of oncology-related proteins and peptides
PCT/US2013/030059 Ceased WO2013151663A1 (en) 2012-04-02 2013-03-09 Modified polynucleotides for the production of membrane proteins
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Cited By (181)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8822663B2 (en) 2010-08-06 2014-09-02 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
WO2014113089A3 (en) * 2013-01-17 2014-09-12 Moderna Therapeutics, Inc. Signal-sensor polynucleotides for the alteration of cellular phenotypes
WO2015034928A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Chimeric polynucleotides
WO2015034925A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Circular polynucleotides
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
US8999380B2 (en) 2012-04-02 2015-04-07 Moderna Therapeutics, Inc. Modified polynucleotides for the production of biologics and proteins associated with human disease
WO2015051214A1 (en) 2013-10-03 2015-04-09 Moderna Therapeutics, Inc. Polynucleotides encoding low density lipoprotein receptor
US9107886B2 (en) 2012-04-02 2015-08-18 Moderna Therapeutics, Inc. Modified polynucleotides encoding basic helix-loop-helix family member E41
US9181321B2 (en) 2013-03-14 2015-11-10 Shire Human Genetic Therapies, Inc. CFTR mRNA compositions and related methods and uses
US9186372B2 (en) 2011-12-16 2015-11-17 Moderna Therapeutics, Inc. Split dose administration
US9212228B2 (en) 2005-11-24 2015-12-15 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US9308281B2 (en) 2011-06-08 2016-04-12 Shire Human Genetic Therapies, Inc. MRNA therapy for Fabry disease
US9334328B2 (en) 2010-10-01 2016-05-10 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
EP2964774A4 (en) * 2013-03-08 2016-08-10 Univ Colorado Regents PTD SMAD7 THERAPEUTICS
US9428535B2 (en) 2011-10-03 2016-08-30 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US9512456B2 (en) 2012-08-14 2016-12-06 Modernatx, Inc. Enzymes and polymerases for the synthesis of RNA
US9512232B2 (en) 2012-05-09 2016-12-06 Ganymed Pharmaceuticals Ag Antibodies against Claudin 18.2 useful in cancer diagnosis
US9522176B2 (en) 2013-10-22 2016-12-20 Shire Human Genetic Therapies, Inc. MRNA therapy for phenylketonuria
US9533047B2 (en) 2011-03-31 2017-01-03 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9597380B2 (en) 2012-11-26 2017-03-21 Modernatx, Inc. Terminally modified RNA
US9629804B2 (en) 2013-10-22 2017-04-25 Shire Human Genetic Therapies, Inc. Lipid formulations for delivery of messenger RNA
US9670261B2 (en) 2012-12-21 2017-06-06 Sanofi Functionalized exendin-4 derivatives
US9668980B2 (en) 2014-07-02 2017-06-06 Rana Therapeutics, Inc. Encapsulation of messenger RNA
US9694053B2 (en) 2013-12-13 2017-07-04 Sanofi Dual GLP-1/glucagon receptor agonists
EP3052106A4 (en) * 2013-09-30 2017-07-19 ModernaTX, Inc. Polynucleotides encoding immune modulating polypeptides
WO2017127750A1 (en) * 2016-01-22 2017-07-27 Modernatx, Inc. Messenger ribonucleic acids for the production of intracellular binding polypeptides and methods of use thereof
US9751926B2 (en) 2013-12-13 2017-09-05 Sanofi Dual GLP-1/GIP receptor agonists
US9750788B2 (en) 2013-12-13 2017-09-05 Sanofi Non-acylated exendin-4 peptide analogues
US9758561B2 (en) 2014-04-07 2017-09-12 Sanofi Dual GLP-1/glucagon receptor agonists derived from exendin-4
US9771406B2 (en) 2014-04-07 2017-09-26 Sanofi Peptidic dual GLP-1/glucagon receptor agonists derived from exendin-4
US9775785B2 (en) 2004-05-18 2017-10-03 Ganymed Pharmaceuticals Ag Antibody to genetic products differentially expressed in tumors and the use thereof
US9775904B2 (en) 2014-04-07 2017-10-03 Sanofi Exendin-4 derivatives as peptidic dual GLP-1/glucagon receptor agonists
WO2017173321A1 (en) * 2016-03-31 2017-10-05 Neon Therapeutics, Inc. Neoantigens and methods of their use
US9789165B2 (en) 2013-12-13 2017-10-17 Sanofi Exendin-4 peptide analogues as dual GLP-1/GIP receptor agonists
US9850269B2 (en) 2014-04-25 2017-12-26 Translate Bio, Inc. Methods for purification of messenger RNA
WO2018009838A1 (en) 2016-07-07 2018-01-11 Rubius Therapeutics, Inc. Compositions and methods related to therapeutic cell systems expressing exogenous rna
WO2018035451A1 (en) 2016-08-19 2018-02-22 Calimmune, Inc. Methods and compositions for treating conditions using recombinant self-complementary adeno-associated virus
US9932381B2 (en) 2014-06-18 2018-04-03 Sanofi Exendin-4 derivatives as selective glucagon receptor agonists
US9943595B2 (en) 2014-12-05 2018-04-17 Translate Bio, Inc. Messenger RNA therapy for treatment of articular disease
US9957499B2 (en) 2013-03-14 2018-05-01 Translate Bio, Inc. Methods for purification of messenger RNA
US9956271B2 (en) 2010-11-30 2018-05-01 Translate Bio, Inc. mRNA for use in treatment of human genetic diseases
US9982029B2 (en) 2015-07-10 2018-05-29 Sanofi Exendin-4 derivatives as selective peptidic dual GLP-1/glucagon receptor agonists
WO2018104538A1 (en) * 2016-12-08 2018-06-14 Curevac Ag Rna for treatment or prophylaxis of a liver disease
US10022455B2 (en) 2014-05-30 2018-07-17 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
WO2018157009A1 (en) * 2017-02-24 2018-08-30 Modernatx, Inc. Nucleic acid-based therapy of muscular dystrophies
US10077439B2 (en) 2013-03-15 2018-09-18 Modernatx, Inc. Removal of DNA fragments in mRNA production process
US10087247B2 (en) 2013-03-14 2018-10-02 Translate Bio, Inc. Methods and compositions for delivering mRNA coded antibodies
US10106800B2 (en) 2005-09-28 2018-10-23 Biontech Ag Modification of RNA, producing an increased transcript stability and translation efficiency
EP3122878B1 (en) 2014-03-24 2018-10-24 Translate Bio, Inc. Mrna therapy for the treatment of ocular diseases
JP2018532777A (ja) * 2015-10-22 2018-11-08 モデルナティーエックス， インコーポレイテッド 癌ワクチン
US10130649B2 (en) 2013-03-15 2018-11-20 Translate Bio, Inc. Synergistic enhancement of the delivery of nucleic acids via blended formulations
US10138507B2 (en) 2013-03-15 2018-11-27 Modernatx, Inc. Manufacturing methods for production of RNA transcripts
US10138213B2 (en) 2014-06-24 2018-11-27 Translate Bio, Inc. Stereochemically enriched compositions for delivery of nucleic acids
US10144942B2 (en) 2015-10-14 2018-12-04 Translate Bio, Inc. Modification of RNA-related enzymes for enhanced production
US10155031B2 (en) 2012-11-28 2018-12-18 Biontech Rna Pharmaceuticals Gmbh Individualized vaccines for cancer
WO2018231990A2 (en) 2017-06-14 2018-12-20 Modernatx, Inc. Polynucleotides encoding methylmalonyl-coa mutase
US10172924B2 (en) 2015-03-19 2019-01-08 Translate Bio, Inc. MRNA therapy for pompe disease
US10207010B2 (en) 2015-12-10 2019-02-19 Modernatx, Inc. Compositions and methods for delivery of agents
WO2019040367A1 (en) * 2017-08-19 2019-02-28 Ohio State Innovation Foundation NEW CANCER IMAGING AGENTS BASED ON PEPTIDES
US10245229B2 (en) 2012-06-08 2019-04-02 Translate Bio, Inc. Pulmonary delivery of mRNA to non-lung target cells
US10258698B2 (en) 2013-03-14 2019-04-16 Modernatx, Inc. Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions
US10266843B2 (en) 2016-04-08 2019-04-23 Translate Bio, Inc. Multimeric coding nucleic acid and uses thereof
US10286086B2 (en) 2014-06-19 2019-05-14 Modernatx, Inc. Alternative nucleic acid molecules and uses thereof
US20190175690A1 (en) * 2016-08-16 2019-06-13 Children's Medical Center Corporation Compositions and methods for cardiac repair
US10350265B2 (en) 2010-09-22 2019-07-16 The Regents Of The University Of Colorado, A Body Corporate Therapeutic applications of Smad7
US10385088B2 (en) 2013-10-02 2019-08-20 Modernatx, Inc. Polynucleotide molecules and uses thereof
CN110167576A (zh) * 2016-09-21 2019-08-23 威斯塔解剖学和生物学研究所 靶向成纤维细胞活化蛋白的优化的合成共有免疫原性组合物
US10407683B2 (en) 2014-07-16 2019-09-10 Modernatx, Inc. Circular polynucleotides
US10414824B2 (en) 2002-11-22 2019-09-17 Ganymed Pharmaceuticals Ag Genetic products differentially expressed in tumors and the use thereof
WO2019118766A3 (en) * 2017-12-13 2019-09-19 Inovio Pharmaceuticals, Inc. Cancer vaccines targeting survivin and uses thereof
WO2019197567A2 (en) 2018-04-11 2019-10-17 Enterome S.A. Antigenic peptides for prevention and treatment of cancer
US10485884B2 (en) 2012-03-26 2019-11-26 Biontech Rna Pharmaceuticals Gmbh RNA formulation for immunotherapy
US10501513B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
WO2019236593A1 (en) * 2018-06-05 2019-12-12 The Trustees Of The University Of Pennsylvania Compositions and methods of muscle specific kinase chimeric autoantibody receptor cells
JP2020506189A (ja) * 2017-02-01 2020-02-27 モデルナティーエックス， インコーポレイテッド Ｒｎａ癌ワクチン
US10576166B2 (en) 2009-12-01 2020-03-03 Translate Bio, Inc. Liver specific delivery of messenger RNA
US10590161B2 (en) 2013-03-15 2020-03-17 Modernatx, Inc. Ion exchange purification of mRNA
US10611814B2 (en) 2014-08-29 2020-04-07 Gemoab Monoclonals Gmbh Universal chimeric antigen expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders
US10646549B2 (en) 2016-05-18 2020-05-12 Modernatx, Inc. Polynucleotides encoding interleukin-12 (IL12) and uses thereof
US10738355B2 (en) 2011-05-24 2020-08-11 Tron-Translationale Onkologie An Der Universitätsmedizin Der Johannes Gutenberg-Universität Mainz Ggmbh Individualized vaccines for cancer
US10758592B2 (en) 2012-10-09 2020-09-01 Sanofi Exendin-4 derivatives as dual GLP1/glucagon agonists
US10780052B2 (en) 2013-10-22 2020-09-22 Translate Bio, Inc. CNS delivery of MRNA and uses thereof
US10806797B2 (en) 2015-06-05 2020-10-20 Sanofi Prodrugs comprising an GLP-1/glucagon dual agonist linker hyaluronic acid conjugate
WO2020227194A1 (en) * 2019-05-08 2020-11-12 The Feinstein Institutes For Medical Research Interferon regulatory factor 5 inhibitors and uses thereof
US10835583B2 (en) 2016-06-13 2020-11-17 Translate Bio, Inc. Messenger RNA therapy for the treatment of ornithine transcarbamylase deficiency
US10849920B2 (en) 2015-10-05 2020-12-01 Modernatx, Inc. Methods for therapeutic administration of messenger ribonucleic acid drugs
US20210000975A1 (en) * 2018-03-07 2021-01-07 Icahn School Of Medicine At Mount Sinai Modrna encoding sphingolipid-metabolizing proteins
WO2021094562A2 (en) 2019-11-15 2021-05-20 Enterome S.A. Antigenic peptides for prevention and treatment of b-cell malignancy
US11027025B2 (en) 2013-07-11 2021-06-08 Modernatx, Inc. Compositions comprising synthetic polynucleotides encoding CRISPR related proteins and synthetic sgRNAs and methods of use
JP2021091689A (ja) * 2014-04-23 2021-06-17 モデルナティーエックス， インコーポレイテッド 核酸ワクチン
US11156617B2 (en) 2015-02-12 2021-10-26 BioNTech RNA Pharmaceuticals GbmH Predicting T cell epitopes useful for vaccination
US20210330740A1 (en) * 2020-04-23 2021-10-28 Run-X Corporation Runx3 modified protein for prevention or treatment of cancer
US11167043B2 (en) 2017-12-20 2021-11-09 Translate Bio, Inc. Composition and methods for treatment of ornithine transcarbamylase deficiency
US11174500B2 (en) 2018-08-24 2021-11-16 Translate Bio, Inc. Methods for purification of messenger RNA
US11173190B2 (en) 2017-05-16 2021-11-16 Translate Bio, Inc. Treatment of cystic fibrosis by delivery of codon-optimized mRNA encoding CFTR
US11173120B2 (en) 2014-09-25 2021-11-16 Biontech Rna Pharmaceuticals Gmbh Stable formulations of lipids and liposomes
US11222711B2 (en) 2013-05-10 2022-01-11 BioNTech SE Predicting immunogenicity of T cell epitopes
WO2022009049A1 (en) * 2020-07-06 2022-01-13 Janssen Biotech, Inc. Prostate neoantigens and their uses
US11224642B2 (en) 2013-10-22 2022-01-18 Translate Bio, Inc. MRNA therapy for argininosuccinate synthetase deficiency
US11253605B2 (en) 2017-02-27 2022-02-22 Translate Bio, Inc. Codon-optimized CFTR MRNA
US11254936B2 (en) 2012-06-08 2022-02-22 Translate Bio, Inc. Nuclease resistant polynucleotides and uses thereof
WO2022040275A1 (en) * 2020-08-19 2022-02-24 University Of Massachusetts Development of novel gene therapeutics inflammation-induced bone loss
US11298426B2 (en) 2003-10-14 2022-04-12 BioNTech SE Recombinant vaccines and use thereof
US20220125723A1 (en) 2010-07-06 2022-04-28 Glaxosmithkline Biologicals Sa Lipid formulations with viral immunogens
US20220133911A1 (en) * 2019-02-14 2022-05-05 Cambridge Enterprise Limited Myc, cyclin t1 and/or cdk9 for use in the treatment of degenerative heart and cns disorders
RU2773273C2 (ru) * 2016-03-31 2022-06-01 БАЙОНТЕК ЮЭс ИНК. Неоантигены и способы их использования
US11377470B2 (en) 2013-03-15 2022-07-05 Modernatx, Inc. Ribonucleic acid purification
US11391744B2 (en) 2015-06-08 2022-07-19 Arquer Diagnostic Limited Methods and kits
EP4046629A1 (en) 2021-02-19 2022-08-24 ModernaTX, Inc. Lipid nanoparticle compositions and methods of formulating the same
US11434486B2 (en) 2015-09-17 2022-09-06 Modernatx, Inc. Polynucleotides containing a morpholino linker
US11492628B2 (en) 2015-10-07 2022-11-08 BioNTech SE 3′-UTR sequences for stabilization of RNA
US11519916B2 (en) 2015-06-08 2022-12-06 Arquer Diagnostics Limited Methods for analysing a urine sample
US11547673B1 (en) 2020-04-22 2023-01-10 BioNTech SE Coronavirus vaccine
KR20230018284A (ko) * 2021-07-29 2023-02-07 주식회사 에스엠엘바이오팜 발현 시스템 및 이를 이용한 핵산 기반 백신
US11591614B2 (en) 2017-05-11 2023-02-28 The Trustees Of The University Of Pennsylvania Gene therapy for ceroid lipofuscinoses
US11596645B2 (en) 2010-07-06 2023-03-07 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
WO2023031394A1 (en) 2021-09-03 2023-03-09 CureVac SE Novel lipid nanoparticles for delivery of nucleic acids
US11603399B2 (en) 2013-03-13 2023-03-14 Modernatx, Inc. Long-lived polynucleotide molecules
US20230095010A1 (en) * 2015-01-19 2023-03-30 Technion Research & Development Foundation Limited. Ubiquitin ligase kpc1 promotes processing of p105 nf-kappab1 to p50, eliciting strong tumor suppression
EP4159741A1 (en) 2014-07-16 2023-04-05 ModernaTX, Inc. Method for producing a chimeric polynucleotide encoding a polypeptide having a triazole-containing internucleotide linkage
WO2023069498A1 (en) 2021-10-22 2023-04-27 Senda Biosciences, Inc. Mrna vaccine composition
US11639370B2 (en) 2010-10-11 2023-05-02 Glaxosmithkline Biologicals Sa Antigen delivery platforms
WO2023039654A3 (pt) * 2021-09-17 2023-05-04 Fundação Oswaldo Cruz Aptâmero de ácido nucleico, composição, uso de um aptâmero, kit diagnóstico, método para detectar ou diagnosticar um tumor, e, método para tratamento de câncer
WO2023073228A1 (en) 2021-10-29 2023-05-04 CureVac SE Improved circular rna for expressing therapeutic proteins
US11655475B2 (en) 2010-07-06 2023-05-23 Glaxosmithkline Biologicals Sa Immunisation of large mammals with low doses of RNA
WO2023096858A1 (en) 2021-11-23 2023-06-01 Senda Biosciences, Inc. A bacteria-derived lipid composition and use thereof
WO2023122080A1 (en) 2021-12-20 2023-06-29 Senda Biosciences, Inc. Compositions comprising mrna and lipid reconstructed plant messenger packs
WO2023144330A1 (en) 2022-01-28 2023-08-03 CureVac SE Nucleic acid encoded transcription factor inhibitors
US11759422B2 (en) 2010-08-31 2023-09-19 Glaxosmithkline Biologicals Sa Pegylated liposomes for delivery of immunogen-encoding RNA
WO2023177904A1 (en) 2022-03-18 2023-09-21 Modernatx, Inc. Sterile filtration of lipid nanoparticles and filtration analysis thereof for biological applications
WO2023150743A3 (en) * 2022-02-07 2023-09-21 Aavogen Inc. Codon-optimized smad7 gene therapy to treat and prevent muscle wasting and to enhance muscle mass
WO2023187127A1 (en) 2022-03-31 2023-10-05 Enterome S.A. Antigenic peptides for prevention and treatment of cancer
US11793867B2 (en) 2017-12-18 2023-10-24 Biontech Us Inc. Neoantigens and uses thereof
US11793843B2 (en) 2019-01-10 2023-10-24 Janssen Biotech, Inc. Prostate neoantigens and their uses
WO2023197001A3 (en) * 2022-04-07 2023-11-16 The Board Of Regents Of The University Of Texas System Compositions and methods for treating liver diseases with sirnas targeting cideb
WO2023227608A1 (en) 2022-05-25 2023-11-30 Glaxosmithkline Biologicals Sa Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide
US11844759B2 (en) 2017-12-15 2023-12-19 Flagship Pioneering Innovations Vi, Llc Compositions comprising circular polyribonucleotides and uses thereof
US11873327B2 (en) 2017-05-18 2024-01-16 Modernatx, Inc. Polynucleotides encoding tethered interleukin-12 (IL12) polypeptides and uses thereof
US11878055B1 (en) 2022-06-26 2024-01-23 BioNTech SE Coronavirus vaccine
US11896636B2 (en) 2011-07-06 2024-02-13 Glaxosmithkline Biologicals Sa Immunogenic combination compositions and uses thereof
WO2024044147A1 (en) 2022-08-23 2024-02-29 Modernatx, Inc. Methods for purification of ionizable lipids
DE202023106198U1 (de) 2022-10-28 2024-03-21 CureVac SE Impfstoff auf Nukleinsäurebasis
US11958886B2 (en) 2016-12-07 2024-04-16 University Of Florida Research Foundation, Incorporated IL-1RA cDNAs
WO2024102434A1 (en) 2022-11-10 2024-05-16 Senda Biosciences, Inc. Rna compositions comprising lipid nanoparticles or lipid reconstructed natural messenger packs
WO2024097521A3 (en) * 2022-11-03 2024-06-13 University Of Massachusetts Compositions for treatment of osteogenesis imperfecta
WO2024159172A1 (en) 2023-01-27 2024-08-02 Senda Biosciences, Inc. A modified lipid composition and uses thereof
WO2024171063A1 (en) * 2023-02-13 2024-08-22 AstraZeneca Ireland Limited Nucleic acids encoding bcl2-associated athanogene 3 (bag3) for gene therapy
WO2024184500A1 (en) 2023-03-08 2024-09-12 CureVac SE Novel lipid nanoparticle formulations for delivery of nucleic acids
WO2024163335A3 (en) * 2023-01-30 2024-10-03 The Board Of Regents Of The University Of Texas System Pten gene therapy vectors and uses thereof
US12109274B2 (en) 2015-09-17 2024-10-08 Modernatx, Inc. Polynucleotides containing a stabilizing tail region
WO2024220712A2 (en) 2023-04-19 2024-10-24 Sail Biomedicines, Inc. Vaccine compositions
WO2024220625A1 (en) 2023-04-19 2024-10-24 Sail Biomedicines, Inc. Delivery of polynucleotides from lipid nanoparticles comprising rna and ionizable lipids
WO2024220752A2 (en) 2023-04-19 2024-10-24 Sail Biomedicines, Inc. Rna therapeutic compositions
US12128113B2 (en) 2016-05-18 2024-10-29 Modernatx, Inc. Polynucleotides encoding JAGGED1 for the treatment of Alagille syndrome
WO2024230934A1 (en) 2023-05-11 2024-11-14 CureVac SE Therapeutic nucleic acid for the treatment of ophthalmic diseases
WO2024238726A1 (en) 2023-05-16 2024-11-21 Omega Therapeutics, Inc. Methods and compositions for modulating methylation of a target gene
WO2024238723A1 (en) 2023-05-16 2024-11-21 Omega Therapeutics, Inc. Methods and compositions for modulating pcsk9 expression
US12151029B2 (en) 2018-09-19 2024-11-26 Modernatx, Inc. PEG lipids and uses thereof
US12173043B2 (en) 2015-10-05 2024-12-24 Immatics Biotechnologies Gmbh Peptides and combination of peptides for use in immunotherapy against small cell lung cancer and other cancers
US12186387B2 (en) 2021-11-29 2025-01-07 BioNTech SE Coronavirus vaccine
US12195505B2 (en) 2018-11-21 2025-01-14 Translate Bio, Inc. Treatment of cystic fibrosis by delivery of nebulized mRNA encoding CFTR
US12194108B2 (en) 2018-03-23 2025-01-14 University Of Massachusetts Gene therapeutics for treating bone disorders
WO2025019742A1 (en) 2023-07-19 2025-01-23 Omega Therapeutics, Inc. Methods and compositions for modulating ctnnb1 expression
US12246067B2 (en) 2018-06-19 2025-03-11 Biontech Us Inc. Neoantigens and uses thereof
WO2025059215A1 (en) 2023-09-12 2025-03-20 Aadigen, Llc Methods and compositions for treating or preventing cancer
WO2025072383A1 (en) 2023-09-25 2025-04-03 The Broad Institute, Inc. Viral open reading frames, uses thereof, and methods of detecting the same
US12270813B2 (en) 2017-06-09 2025-04-08 BioNTech SE Methods for predicting the usefulness of disease specific amino acid modifications for immunotherapy
WO2025097055A2 (en) 2023-11-02 2025-05-08 The Broad Institute, Inc. Compositions and methods of use of t cells in immunotherapy
US12295997B2 (en) 2020-07-06 2025-05-13 Janssen Biotech, Inc. Prostate neoantigens and their uses
US12303561B2 (en) 2017-04-03 2025-05-20 Biontech Us Inc. Protein antigens and uses thereof
US12318443B2 (en) 2016-11-11 2025-06-03 Modernatx, Inc. Influenza vaccine
US12385034B2 (en) 2016-06-24 2025-08-12 Modernatx, Inc. Methods and apparatus for filtration
US12383508B2 (en) 2018-09-19 2025-08-12 Modernatx, Inc. High-purity peg lipids and uses thereof
WO2025194138A1 (en) 2024-03-14 2025-09-18 Tessera Therapeutics, Inc. St1cas9 compositions and methods for modulating a genome
US12419948B2 (en) 2020-08-31 2025-09-23 The Broad Institute, Inc. Immunogenic compositions and use thereof
US12435372B2 (en) 2014-12-19 2025-10-07 The Broad Institute, Inc. Methods for profiling the T-cell-receptor repertoire
WO2025235563A1 (en) 2024-05-07 2025-11-13 Omega Therapeutics, Inc. Epigenetic modulation for upregulation of genes
US12480117B2 (en) 2019-03-25 2025-11-25 Flagship Pioneering Innovations Vi, Llc Compositions comprising modified circular polyribonucleotides and uses thereof

Families Citing this family (647)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9879266B2 (en) 2002-11-14 2018-01-30 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US9308181B2 (en) 2006-03-06 2016-04-12 Nuvo Research Inc. Topical formulations, systems and methods
US9642912B2 (en) 2006-03-06 2017-05-09 Crescita Therapeutics Inc. Topical formulations for treating skin conditions
CA2729096C (en) 2008-06-26 2020-04-28 Acceleron Pharma Inc. Methods for dosing an actriib antagonist and monitoring of treated patients
US10236078B2 (en) 2008-11-17 2019-03-19 Veracyte, Inc. Methods for processing or analyzing a sample of thyroid tissue
JP6078339B2 (ja) 2009-05-07 2017-02-08 ベラサイト インコーポレイテッド 甲状腺状態の診断のための方法および組成物
US9364414B2 (en) 2011-02-01 2016-06-14 Isp Investments Inc. Method to protect skin from ultraviolet radiation using novel peptides involved in the improvement of microparasol organization in keratinocytes
FR2970968A1 (fr) * 2011-02-01 2012-08-03 Isp Investments Inc Nouveaux peptides intervenant dans la voie de signalisation scf c-kit et compositions les comprenant
ES2987057T3 (es) 2011-06-08 2024-11-13 Translate Bio Inc Lípidos escindibles
PT2717898T (pt) 2011-06-10 2019-05-20 Bioverativ Therapeutics Inc Compostos pró-coagulantes e processos para a sua utilização
US9442092B2 (en) 2011-06-20 2016-09-13 Kerry Lane Methods for treatment of autism
ES2748038T3 (es) 2011-07-01 2020-03-12 Ngm Biopharmaceuticals Inc Composiciones, usos y métodos para el tratamiento de trastornos y enfermedades metabólicos
WO2013053076A1 (en) 2011-10-10 2013-04-18 Zensun （Shanghai）Science & Technology Limited Compositions and methods for treating heart failure
WO2013075008A1 (en) 2011-11-16 2013-05-23 University Of Florida Research Foundation Inc. Aav dual vector systems for gene therapy
US8497124B2 (en) 2011-12-05 2013-07-30 Factor Bioscience Inc. Methods and products for reprogramming cells to a less differentiated state
MX354995B (es) 2011-12-05 2018-03-27 Factor Bioscience Inc Metodos y productos para transfeccion de celulas.
EP2756093A4 (en) 2012-02-01 2015-07-01 Compugen Ltd C10RF32 ANTIBODIES AND USES THEREOF FOR THE TREATMENT OF CANCER
US10689609B2 (en) 2012-03-15 2020-06-23 Flodesign Sonics, Inc. Acoustic bioreactor processes
US9745548B2 (en) 2012-03-15 2017-08-29 Flodesign Sonics, Inc. Acoustic perfusion devices
US10322949B2 (en) 2012-03-15 2019-06-18 Flodesign Sonics, Inc. Transducer and reflector configurations for an acoustophoretic device
US10704021B2 (en) 2012-03-15 2020-07-07 Flodesign Sonics, Inc. Acoustic perfusion devices
US9458450B2 (en) 2012-03-15 2016-10-04 Flodesign Sonics, Inc. Acoustophoretic separation technology using multi-dimensional standing waves
US9950282B2 (en) 2012-03-15 2018-04-24 Flodesign Sonics, Inc. Electronic configuration and control for acoustic standing wave generation
US10967298B2 (en) 2012-03-15 2021-04-06 Flodesign Sonics, Inc. Driver and control for variable impedence load
US9752113B2 (en) 2012-03-15 2017-09-05 Flodesign Sonics, Inc. Acoustic perfusion devices
DK2830595T3 (da) 2012-03-29 2019-12-02 Translate Bio Inc Ioniserbare kationiske lipider
EP3865123A1 (en) 2012-03-29 2021-08-18 Translate Bio, Inc. Lipid-derived neutral nanoparticles
US10737953B2 (en) 2012-04-20 2020-08-11 Flodesign Sonics, Inc. Acoustophoretic method for use in bioreactors
US9534218B2 (en) * 2012-06-18 2017-01-03 Dow Agrosciences Llc Expression of maize codon optimized proteins in pseudomonas fluorescens
WO2014093924A1 (en) * 2012-12-13 2014-06-19 Moderna Therapeutics, Inc. Modified nucleic acid molecules and uses thereof
EP2913396B1 (en) 2012-10-29 2018-08-29 Saitama Medical University Method of manufacturing differentiated pluripotent stem cell
KR102315098B1 (ko) 2012-11-01 2021-10-21 팩터 바이오사이언스 인크. 세포에서 단백질을 발현시키는 방법들과 생성물들
US9290557B2 (en) 2012-11-28 2016-03-22 Ngm Biopharmaceuticals, Inc. Compositions comprising variants and fusions of FGF19 polypeptides
EP2925775B1 (en) 2012-11-28 2020-09-16 NGM Biopharmaceuticals, Inc. Compositions and methods for treatment of metabolic disorders and diseases
BR112015013784A2 (pt) 2012-12-12 2017-07-11 Massachusetts Inst Technology aplicação, manipulação e otimização de sistemas, métodos e composições para manipulação de sequência e aplicações terapêuticas
WO2014093701A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
US9273107B2 (en) 2012-12-27 2016-03-01 Ngm Biopharmaceuticals, Inc. Uses and methods for modulating bile acid homeostasis and treatment of bile acid disorders and diseases
EP2938740B1 (en) 2012-12-27 2022-04-20 NGM Biopharmaceuticals, Inc. Chimeric fgf19 peptides for use in treating bile acid disorders
EP2749569A1 (en) 2012-12-28 2014-07-02 Annibale Alessandro Puca Variant of BPIFB4 protein
PL2956477T5 (pl) 2013-02-15 2024-05-27 Bioverativ Therapeutics Inc. Zoptymalizowany gen czynnika viii
US10526655B2 (en) 2013-03-14 2020-01-07 Veracyte, Inc. Methods for evaluating COPD status
US9944918B2 (en) 2013-03-15 2018-04-17 The United States Of America, As Represented By The Secretary, Dept. Of Health & Human Services Synthetic methylmalonyl-CoA mutase transgene for the treatment of MUT class methylmalonic acidemia (MMA)
WO2014143884A2 (en) * 2013-03-15 2014-09-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Synthetic methylmalonyl-coa mutase transgene for the treatment of mut class methylmalonic acidemia (mma)
US11976329B2 (en) 2013-03-15 2024-05-07 Veracyte, Inc. Methods and systems for detecting usual interstitial pneumonia
EP3524618B1 (en) 2013-03-15 2023-03-08 GLAdiator Biosciences, Inc. Gla domains as targeting agents
BR112015029293A2 (pt) 2013-05-22 2018-04-24 Zensun Shanghai Science & Tech Ltd método e kit para prevenir, tratar ou retardar uma doença ou distúrbio cardiovascular em um mamífero
EP3011033B1 (en) 2013-06-17 2020-02-19 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
WO2014205338A2 (en) * 2013-06-21 2014-12-24 President And Fellows Of Harvard College Methods and compositions relating to modulation of the permeability of the blood brain barrier
EP3021834A1 (en) * 2013-07-18 2016-05-25 MannKind Corporation Heat-stable dry powder pharmaceutical compositions and methods
CA2919828C (en) 2013-07-30 2022-07-19 Phaserx, Inc. Block copolymers and their conjugates or complexes with oligonucleotides
SG10201801428RA (en) * 2013-08-21 2018-03-28 Curevac Ag Method for increasing expression of rna-encoded proteins
US9745569B2 (en) 2013-09-13 2017-08-29 Flodesign Sonics, Inc. System for generating high concentration factors for low cell density suspensions
US20160264614A1 (en) * 2013-10-02 2016-09-15 Moderna Therapeutics, Inc. Polynucleotide molecules and uses thereof
KR102178945B1 (ko) 2013-10-28 2020-11-13 엔지엠 바이오파마슈티컬스, 아이엔씨. 암 모델 및 관련 방법
EP3068378A4 (en) * 2013-11-12 2017-05-03 University Of Washington Through Its Center For Commercialization Random copolymer therapeutic agent carriers and assemblies thereof
US10772974B2 (en) 2013-11-18 2020-09-15 Beth Israel Deaconess Medical Center, Inc. Compositions and methods for cardiac regeneration
WO2015089473A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
KR20160089530A (ko) 2013-12-12 2016-07-27 더 브로드 인스티튜트, 인코퍼레이티드 Ｈｂｖ 및 바이러스 질병 및 질환을 위한 ｃｒｉｓｐｒ­ｃａｓ 시스템 및 조성물의 전달，용도 및 치료적 적용
WO2015089351A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
JP2017501149A (ja) * 2013-12-12 2017-01-12 ザ・ブロード・インスティテュート・インコーポレイテッド 粒子送達構成成分を用いた障害及び疾患の標的化のためのｃｒｉｓｐｒ−ｃａｓ系及び組成物の送達、使用及び治療適用
US9480731B2 (en) * 2013-12-12 2016-11-01 Medy-Tox, Inc. Long lasting effect of new botulinum toxin formulations
EP2918275B1 (en) * 2013-12-13 2016-05-18 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
GB201322574D0 (en) * 2013-12-19 2014-02-05 Equigerminal Sa Retroviral peptides
CN110946993A (zh) * 2014-01-03 2020-04-03 上海泽生科技开发股份有限公司 纽兰格林制剂的配方
US9725710B2 (en) 2014-01-08 2017-08-08 Flodesign Sonics, Inc. Acoustophoresis device with dual acoustophoretic chamber
RU2682335C2 (ru) * 2014-01-17 2019-03-19 Сидарс-Синай Медикал Сентр Рецептор-направленные конструкции и их применение
PE20170256A1 (es) 2014-01-24 2017-04-22 Ngm Biopharmaceuticals Inc Proteinas de union y sus metodos de uso
RU2714404C2 (ru) * 2014-01-31 2020-02-14 Фэктор Байосайенс Инк. Способы и продукты для получения и доставки нуклеиновых кислот
WO2015130832A1 (en) * 2014-02-25 2015-09-03 The Regents Of The University Of California Agents for enhancement of production of biofuel precursors in microalgae
SI3116900T1 (sl) 2014-03-09 2021-02-26 The Trustees Of The University Of Pennsylvania Sestavki uporabni pri zdravljenju pomanjkanja ornitin transkarbamilaze(OTC)
UA120050C2 (uk) 2014-03-21 2019-09-25 Джензайм Корпорейшн Генна терапія для лікування пігментного ретиніту
SG11201608389RA (en) * 2014-04-07 2016-11-29 Minerva Biotechnologies Corp Anti-nme antibody
CA2945965C (en) * 2014-04-15 2022-11-01 Applied Genetic Technologies Corporation Codon optimized nucleic acid encoding a retinitis pigmentosa gtpase regulator (rpgr)
KR101791296B1 (ko) * 2014-04-17 2017-10-27 제주대학교 산학협력단 알츠하이머병 관련 돌연변이 유전자를 포함하는 발현 카세트, 벡터, 및 이를 이용하여 형질전환된 세포주
KR102092225B1 (ko) 2014-04-30 2020-03-23 주식회사 엘지화학 고효율 분비능을 가지는 단백질 분비 인자 및 이를 포함하는 발현 벡터
WO2015175748A1 (en) * 2014-05-14 2015-11-19 Evorx Technologies, Inc. Methods and compositions for controlling gene expression and treating cancer
EP3143146B1 (en) * 2014-05-14 2020-05-20 Esteve Pharmaceuticals, S.A. Adenoassociated virus vectors for the treatment of lysosomal storage disorders
US10398758B2 (en) 2014-05-28 2019-09-03 Ngm Biopharmaceuticals, Inc. Compositions comprising variants of FGF19 polypeptides and uses thereof for the treatment of hyperglycemic conditions
EP3149167B1 (en) * 2014-05-30 2019-09-04 Academia Sinica Aptamer targeting mage-a3 peptide and uses thereof
CN106795224B (zh) * 2014-06-04 2021-05-18 阿塞勒隆制药公司 用促滤泡素抑制素多肽治疗病症的方法和组合物
US10010498B2 (en) 2014-06-04 2018-07-03 Acceleron Pharma Inc. Methods for treatment of amyotrophic lateral sclerosis with follistatin fusion proteins
CA2951707A1 (en) 2014-06-10 2015-12-17 Massachusetts Institute Of Technology Method for gene editing
EP3155129B1 (en) * 2014-06-10 2019-01-16 CureVac AG Method for enhancing rna production
WO2015195509A2 (en) 2014-06-16 2015-12-23 Ngm Biopharmaceuticals, Inc. Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases
US20170175129A1 (en) * 2014-06-19 2017-06-22 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
WO2016004113A1 (en) 2014-06-30 2016-01-07 Biogen Ma Inc. Optimized factor ix gene
US9744483B2 (en) 2014-07-02 2017-08-29 Flodesign Sonics, Inc. Large scale acoustic separation device
EP3166626B1 (en) 2014-07-11 2021-04-28 Biostrategies LC Materials and methods for treating disorders associated with sulfatase enzymes
US12297505B2 (en) 2014-07-14 2025-05-13 Veracyte, Inc. Algorithms for disease diagnostics
ES2715889T3 (es) * 2014-07-25 2019-06-06 Shire Human Genetic Therapies Estructura cristalina del dominio de tipo proteína de transferencia de glicolípidos de la proteína adaptadora de cuatro fosfatos 2 humana
WO2016027842A1 (ja) * 2014-08-20 2016-02-25 和光純薬工業株式会社 幹細胞の分化状態の判定方法及びこれに用いられる新規な分化マーカー
JP6643324B2 (ja) * 2014-09-02 2020-02-12 アメリカン シルヴァー リミテッド ライアビリティ カンパニー ボツリヌス毒素及びコロイド状銀粒子
TW201617368A (zh) 2014-09-05 2016-05-16 史坦森特瑞斯公司 新穎抗ｍｆｉ２抗體及使用方法
US20160090577A1 (en) * 2014-09-26 2016-03-31 Dow Agrosciences Llc Heterologous expression of glycine n-acyltransferase proteins
AU2015323944B2 (en) * 2014-10-01 2018-11-29 Inovio Pharmaceuticals, Inc. Vaccines having an antigen and interleukin-21 as an adjuvant
US10385380B2 (en) 2014-10-02 2019-08-20 The Regents Of The University Of California Personalized protease assay to measure protease activity in neoplasms
JP6842410B2 (ja) 2014-10-03 2021-03-17 ユニバーシティ オブ マサチューセッツ 新規の高効率ライブラリーにより同定されるａａｖベクター
WO2016054554A1 (en) 2014-10-03 2016-04-07 University Of Massachusetts Heterologous targeting peptide grafted aavs
JOP20200115A1 (ar) * 2014-10-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات))
CN105561298A (zh) 2014-10-17 2016-05-11 上海泽生科技开发有限公司 神经调节蛋白用于预防、治疗或延迟射血分数保留的心力衰竭的方法和组合物
IL251834B2 (en) 2014-10-23 2023-09-01 Ngm Biopharmaceuticals Inc Pharmaceutical compositions containing peptide variants and methods of using them
JP6384863B2 (ja) * 2014-10-24 2018-09-05 国立大学法人北海道大学 脂質膜構造体
EP3212793B1 (en) * 2014-11-02 2020-01-08 Arcturus Therapeutics, Inc. Messenger una molecules and uses thereof
US20170335396A1 (en) 2014-11-05 2017-11-23 Veracyte, Inc. Systems and methods of diagnosing idiopathic pulmonary fibrosis on transbronchial biopsies using machine learning and high dimensional transcriptional data
US11827680B2 (en) * 2014-11-06 2023-11-28 Case Western Reserve University Compounds and methods of treating usher syndrome III
US10434144B2 (en) 2014-11-07 2019-10-08 Ngm Biopharmaceuticals, Inc. Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders
KR102647743B1 (ko) * 2014-11-10 2024-03-14 에트리스 게엠베하 Bmp 인코딩 rna의 전달에 의한 골형성 유도
EP3218508A4 (en) 2014-11-10 2018-04-18 Modernatx, Inc. Multiparametric nucleic acid optimization
EP3461904A1 (en) 2014-11-10 2019-04-03 ModernaTX, Inc. Alternative nucleic acid molecules containing reduced uracil content and uses thereof
RU2597789C2 (ru) * 2014-11-10 2016-09-20 Илья Владимирович Духовлинов Анальгетическое средство на основе плазмидной днк, кодирующей hnp-1, либо hnp-2, либо hnp-3 (варианты)
WO2016077625A1 (en) 2014-11-12 2016-05-19 Stayton Patrick S Stabilized polymeric carriers for therapeutic agent delivery
US10653782B2 (en) * 2014-11-25 2020-05-19 Nortwestern University Retroviral particles expressing Sirt1 embedded within PPCN
EP3233107B1 (en) * 2014-12-09 2021-01-27 Wentao Zhang Nbp158 and uses thereof
ES2926020T3 (es) 2014-12-12 2022-10-21 Curevac Ag Moléculas de ácido nucleico artificiales para una expresión proteica mejorada
RU2709778C2 (ru) 2014-12-23 2019-12-20 Эйвон Продактс, Инк. Пептиды и их применение в уходе за кожей
WO2016105536A2 (en) * 2014-12-23 2016-06-30 University Of Maryland, Baltimore Muc1 decoy peptides for treatment and prevention of bacterial infections
EP3702456A1 (en) 2014-12-24 2020-09-02 The Broad Institute, Inc. Crispr having or associated with destabilization domains
US10335498B2 (en) * 2014-12-29 2019-07-02 University Of Iowa Research Foundation RNA based biomaterial for tissue engineering applications
WO2016118697A1 (en) 2015-01-21 2016-07-28 Phaserx, Inc. Methods, compositions, and systems for delivering therapeutic and diagnostic agents into cells
MA41414A (fr) 2015-01-28 2017-12-05 Centre Nat Rech Scient Protéines de liaison agonistes d' icos
CA2976376A1 (en) * 2015-02-13 2016-08-18 Factor Bioscience Inc. Nucleic acid products and methods of administration thereof
WO2016131009A1 (en) 2015-02-13 2016-08-18 University Of Massachusetts Compositions and methods for transient delivery of nucleases
WO2016138387A1 (en) * 2015-02-27 2016-09-01 The Charlotte-Mecklenburg Hospital Authority D/B/A Carolinas Healthcare System Methods and compositions for treating dystroglycanopathy disorders
WO2016141347A2 (en) * 2015-03-04 2016-09-09 Wayne State University Systems and methods to diagnose sarcoidosis and identify markers of the condition
WO2016153995A1 (en) * 2015-03-20 2016-09-29 The Trustees Of The University Of Pennsylvania Vaccines with cd40 ligand as an adjuvant
KR20170129233A (ko) 2015-03-26 2017-11-24 악셀레론 파마 인코포레이티드 폴리스타틴-관련된 융합 단백질 및 이들의 용도
GB201505305D0 (en) 2015-03-27 2015-05-13 Immatics Biotechnologies Gmbh Novel Peptides and combination of peptides for use in immunotherapy against various tumors
RS64397B1 (sr) 2015-03-27 2023-08-31 Immatics Biotechnologies Gmbh Novi peptidi i kombinacija peptida za upotrebu u imunoterapiji protiv raznih tumora (seq id 25 - mrax5-003)
GB201505585D0 (en) 2015-03-31 2015-05-13 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides and scaffolds for use in immunotherapy against renal cell carinoma (RCC) and other cancers
EP3286209B1 (en) 2015-04-24 2020-11-25 Ferring BV Method of production of gonadotrophin
US11377651B2 (en) 2016-10-19 2022-07-05 Flodesign Sonics, Inc. Cell therapy processes utilizing acoustophoresis
US11708572B2 (en) 2015-04-29 2023-07-25 Flodesign Sonics, Inc. Acoustic cell separation techniques and processes
US11021699B2 (en) 2015-04-29 2021-06-01 FioDesign Sonics, Inc. Separation using angled acoustic waves
CN104878091B (zh) * 2015-04-30 2019-05-17 北京大北农科技集团股份有限公司 用于检测玉米植物dbn9978的核酸序列及其检测方法
US20180346988A1 (en) * 2015-05-04 2018-12-06 The Brigham And Women's Hospital, Inc. Znf532 for diagnosis and treatment of cancer
WO2016180430A1 (en) * 2015-05-08 2016-11-17 Curevac Ag Method for producing rna
GB201508025D0 (en) 2015-05-11 2015-06-24 Ucl Business Plc Fabry disease gene therapy
BR112017024115A2 (pt) * 2015-05-12 2018-08-07 Sangamo Therapeutics Inc regulação de expressão genética mediada por nuclease
US20180245074A1 (en) * 2015-06-04 2018-08-30 Protiva Biotherapeutics, Inc. Treating hepatitis b virus infection using crispr
US10626393B2 (en) 2015-06-04 2020-04-21 Arbutus Biopharma Corporation Delivering CRISPR therapeutics with lipid nanoparticles
US11084852B2 (en) 2015-06-15 2021-08-10 Oklahoma Medical Research Foundation Ubiquitin interacting motif peptides as therapeutics
IL316159A (en) 2015-06-15 2024-12-01 Mpeg La Llc Defined Oligonucleotide Multimers and Methods for Manufacture Thereof
US9597274B2 (en) * 2015-06-17 2017-03-21 Avon Products, Inc. Peptides and their use in the treatment of skin
WO2016205759A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation
TWI747524B (zh) 2015-06-19 2021-11-21 德商英麥提克生物技術股份有限公司 用於免疫治療的新穎胜肽及胜肽組合物與產生用於抗胰臟癌及其他癌症的支架的方法
GB201510771D0 (en) 2015-06-19 2015-08-05 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy and methods for generating scaffolds for the use against pancreatic cancer
US12404552B2 (en) * 2015-07-17 2025-09-02 Allele Biotechnology & Pharmaceuticals, Inc. Methods of selecting antibodies and antibody fragments
US11364292B2 (en) 2015-07-21 2022-06-21 Modernatx, Inc. CHIKV RNA vaccines
MA42502A (fr) 2015-07-21 2018-05-30 Modernatx Inc Vaccins contre une maladie infectieuse
US11474085B2 (en) 2015-07-28 2022-10-18 Flodesign Sonics, Inc. Expanded bed affinity selection
US11459540B2 (en) 2015-07-28 2022-10-04 Flodesign Sonics, Inc. Expanded bed affinity selection
AU2016298108B2 (en) * 2015-07-28 2022-07-21 Lankenau Institute For Medical Research Methods and compositions for the treatment of immunomodulatory diseases and disorders
WO2017019957A2 (en) 2015-07-29 2017-02-02 Ngm Biopharmaceuticals, Inc. Binding proteins and methods of use thereof
WO2017020026A1 (en) 2015-07-30 2017-02-02 Modernatx, Inc. Concatemeric peptide epitopes rnas
GB201513921D0 (en) 2015-08-05 2015-09-23 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers
WO2017031232A1 (en) 2015-08-17 2017-02-23 Modernatx, Inc. Methods for preparing particles and related compositions
US10808242B2 (en) 2015-08-28 2020-10-20 Biontech Rna Pharmaceuticals Gmbh Method for reducing immunogenicity of RNA
GB201515321D0 (en) 2015-08-28 2015-10-14 Immatics Biotechnologies Gmbh Novel peptides, combination of peptides and scaffolds for use in immunotherapeutic treatment of various cancers
US12258567B2 (en) * 2015-08-28 2025-03-25 CureVac SE Artificial nucleic acid molecules
IL292864A (en) 2015-08-28 2022-07-01 Immatics Biotechnologies Gmbh Novel peptides, combination of peptides and scaffolds for use in immunotherapeutic treatment of various cancers
CN108026160A (zh) * 2015-09-07 2018-05-11 德国亥姆霍兹慕尼黑中心健康与环境研究中心（有限公司） 新型igfr-样受体及其用途
GB201516066D0 (en) * 2015-09-10 2015-10-28 Young & Co Llp D Treatment of retinitis pigmentosa
US20190054112A1 (en) * 2015-09-18 2019-02-21 Moderna Therapeutics, Inc. Polynucleotide formulations for use in the treatment of renal diseases
HUE065704T2 (hu) * 2015-09-21 2024-06-28 Trilink Biotechnologies Llc Készítmények és módszerek 5-sapkával ellátott RNS-ek szintetizálására
DK3353196T5 (da) * 2015-09-22 2024-09-30 Inst Nat Sante Rech Med Polypeptider, der er i stand til at inhibere bindingen mellem leptin og neuropilin-1
SG10201912736UA (en) 2015-10-01 2020-02-27 Potenza Therapeutics Inc Anti-tigit antigen-binding proteins and methods of use thereof
LT3359671T (lt) 2015-10-08 2021-12-10 Dna Twopointo Inc. Dnr vektoriai, transpozonai ir transpozazės, skirti eukariotinio genomo modifikacijai
EP4530350A3 (en) * 2015-10-09 2025-06-25 Genzyme Corporation Improved flare (flow cytometry attenuated reporter expression) technology for rapid bulk sorting
AU2016341131A1 (en) 2015-10-19 2018-05-10 University Of Massachusetts Anti-cancer and anti-inflammatory therapeutics and methods thereof
HUE054802T2 (hu) 2015-10-21 2021-09-28 Us Health Kodon-optimalizált, csökkentett méretû ATP7A cDNS és alkalmazások a rézszállítási zavarok kezelésére
AU2016341311B2 (en) * 2015-10-22 2023-11-16 Modernatx, Inc. Respiratory syncytial virus vaccine
EP3364950A4 (en) 2015-10-22 2019-10-23 ModernaTX, Inc. VACCINES AGAINST TROPICAL DISEASES
EP3364982A4 (en) 2015-10-22 2019-04-17 ModernaTX, Inc. VACCINES AGAINST SEXUALLY TRANSMITTED DISEASES
EA201890999A1 (ru) * 2015-10-22 2018-12-28 МОДЕРНАТиЭкс, ИНК. Вакцина против вируса простого герпеса
EP4349405A3 (en) 2015-10-22 2024-06-19 ModernaTX, Inc. Respiratory virus vaccines
EA201891001A1 (ru) * 2015-10-22 2018-11-30 МОДЕРНАТиЭкс, ИНК. Вакцины на основе нуклеиновых кислот против вируса ветряной оспы (vzv)
WO2017070613A1 (en) 2015-10-22 2017-04-27 Modernatx, Inc. Human cytomegalovirus vaccine
GB201518792D0 (en) * 2015-10-23 2015-12-09 Univ Manchester Production of proteins
AU2016347688A1 (en) * 2015-10-30 2018-06-21 The University Of Melbourne Methods and compositions for improving glucose metabolism
JP7037490B2 (ja) * 2015-11-05 2022-03-16 ザ ジェネラル ホスピタル コーポレイション 副腎脊髄ニューロパチーの治療のためのａｂｃｄ１をコードする核酸配列の髄腔内送達
ES2871036T3 (es) 2015-11-09 2021-10-28 Ngm Biopharmaceuticals Inc Método para el tratamiento de trastornos relacionados con ácidos biliares
IL259178B (en) 2015-11-12 2022-08-01 Res Inst Nationwide Childrens Hospital A vector encoding ano5 for the treatment of muscular dystrophy
HK1257955A1 (zh) 2015-11-16 2019-11-01 The Research Institute At Nationwide Children's Hospital 用於治疗肌联蛋白类肌病和其他肌联蛋白病变的材料和方法
US20190307857A1 (en) 2015-12-09 2019-10-10 Modernatx, Inc. MODIFIED mRNA ENCODING A URIDINE DIPHOPSPHATE GLUCURONOSYL TRANSFERASE AND USES THEREOF
HK1255541A1 (zh) * 2015-12-11 2019-08-23 Immatics Biotechnologies Gmbh 用於多种癌症免疫治疗的新型肽和肽组合物
RU2762747C2 (ru) 2015-12-14 2021-12-22 Зе Трастис Оф Зе Юниверсити Оф Пенсильвания Генная терапия офтальмологических нарушений
JP7061067B2 (ja) 2015-12-14 2022-04-27 ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア クリグラー・ナジャー症候群の処置のための組成物
GB201522243D0 (en) * 2015-12-16 2016-01-27 Ucl Business Plc Treatment
CA3007108A1 (en) 2015-12-17 2017-06-22 Modernatx, Inc. Polynucleotides encoding methylmalonyl-coa mutase
JOP20200228A1 (ar) 2015-12-21 2017-06-16 Novartis Ag تركيبات وطرق لخفض تعبير البروتين tau
US10465190B1 (en) 2015-12-23 2019-11-05 Modernatx, Inc. In vitro transcription methods and constructs
PL3394093T3 (pl) 2015-12-23 2022-05-16 Modernatx, Inc. Metody stosowania polinukleotydów kodujących ligand ox40
EP3400023A1 (en) 2016-01-10 2018-11-14 ModernaTX, Inc. Therapeutic mrnas encoding anti ctla-4 antibodies
HUE051774T2 (hu) * 2016-01-13 2021-03-29 Genzyme Corp Oszteoprotektív géneket, például HAS2-t és lubricint expresszáló rekombináns AAV vektorok, amelyek alkalmazhatók emlõsben oszteoartritisz és azzal kapcsolatos ízületi állapotok kezelésében
PT3411478T (pt) 2016-02-01 2022-09-13 Bioverativ Therapeutics Inc Genes do fator viii otimizados
WO2017136399A1 (en) * 2016-02-02 2017-08-10 Idera Pharmaceuticals, Inc. POTENTIATION OF mmRNA THERAPEUTICS
EP3410849B1 (en) 2016-02-05 2023-07-05 Institut Pasteur Use of inhibitors of adam12 as adjuvants in tumor therapies
CA3014773C (en) 2016-03-07 2025-11-18 Father Flanagan's Boys' Home Doing Business As Boys Town National Research Hospital NON-INVASIVE MOLECULAR WITRS
DK3436030T3 (da) 2016-04-01 2022-11-21 Kite Pharma Inc Kimæriske receptorer og fremgangsmåder til anvendelse deraf
US10603380B2 (en) 2016-04-01 2020-03-31 Kite Pharma, Inc. Chimeric antigen and T cell receptors and methods of use
TWI761831B (zh) 2016-04-01 2022-04-21 美商凱特製藥公司 嵌合抗原受體（ｃａｒ）和ｔ細胞受體（ｔｃｒ）及彼等之用途
IL262321B2 (en) * 2016-04-15 2024-09-01 Novartis Ag Preparations and methods for selective protein expression
CA3021057A1 (en) 2016-04-15 2017-10-19 Research Institute At Nationwide Children's Hospital Adeno-associated virus vector delivery of b-sarcoglycan and microrna-29 and the treatment of muscular dystrophy
JP7045362B2 (ja) 2016-04-20 2022-03-31 セントロ デ インベスティガシオンス エネルジェチカス メディオアンビエンタゥス イェ テクノロジカス オー．エイ． エム．ピー． Ｐｋｌｒの遺伝子発現増強のための組成物および方法
CR20200607A (es) 2016-04-21 2021-01-20 Immatics Biotechnologies Gmbh INMUNOTERAPIA CONTRA EL MELANOMA Y OTROS TIPOS DE CÁNCER (Divisional 2018-551)
PE20181897A1 (es) 2016-04-21 2018-12-11 Immatics Biotechnologies Gmbh Inmunoterapia contra el melanoma y otros tipos de cancer
US11596699B2 (en) 2016-04-29 2023-03-07 CureVac SE RNA encoding an antibody
GB2549798A (en) 2016-04-29 2017-11-01 Univ Bradford Peptides and nanoparticle formulations thereof
US11085035B2 (en) 2016-05-03 2021-08-10 Flodesign Sonics, Inc. Therapeutic cell washing, concentration, and separation utilizing acoustophoresis
US11214789B2 (en) 2016-05-03 2022-01-04 Flodesign Sonics, Inc. Concentration and washing of particles with acoustics
US20180126003A1 (en) * 2016-05-04 2018-05-10 Curevac Ag New targets for rna therapeutics
WO2017191274A2 (en) 2016-05-04 2017-11-09 Curevac Ag Rna encoding a therapeutic protein
US12123030B2 (en) 2016-05-18 2024-10-22 Modernatx, Inc. Polynucleotides encoding lipoprotein lipase for the treatment of hyperlipidemia
EP3896164A1 (en) 2016-05-18 2021-10-20 ModernaTX, Inc. Polynucleotides encoding alpha-galactosidase a for the treatment of fabry disease
AU2017266948B2 (en) 2016-05-18 2024-07-04 Fundacion Para La Investigacion Medica Aplicada Polynucleotides encoding porphobilinogen deaminase for the treatment of acute intermittent porphyria
MA45032A (fr) * 2016-05-18 2019-03-27 Fundacion Para La Investig Medica Aplicada Polynucléotides codant pour la porphobilinogène désaminase destinés au traitement de la porphyrie intermittente aiguë
US20190298657A1 (en) * 2016-05-18 2019-10-03 Modernatx, Inc. Polynucleotides Encoding Acyl-CoA Dehydrogenase, Very Long-Chain for the Treatment of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency
AU2017268394A1 (en) 2016-05-18 2019-01-03 Modernatx, Inc. Polynucleotides encoding relaxin
SG11201810162PA (en) 2016-05-18 2018-12-28 Modernatx Inc Polynucleotides encoding citrin for the treatment of citrullinemia type 2
EP3458108A4 (en) 2016-05-18 2020-04-22 ModernaTX, Inc. POLYNUCLEOTIDES ENCODING A CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR FOR THE TREATMENT OF CYSTIC FIBROSIS
MA45041A (fr) 2016-05-18 2019-03-27 Modernatx Inc Polynucléotides codant pour la galactose-1-phosphate uridylyltransférase destinés au traitement de la galactosémie de type 1
LT3458474T (lt) 2016-05-18 2022-10-10 Modernatx, Inc. Imunitetą moduliuojančius polipeptidus koduojančių mrnr deriniai ir jų naudojimas
US10925869B2 (en) 2016-05-26 2021-02-23 University of Pittsburgh—of the Commonwealth System of Higher Education Compositions and methods for treating pulmonary vascular disease
CA3025626A1 (en) * 2016-05-27 2017-11-30 Transcriptx, Inc. Treatment of primary ciliary dyskinesia with synthetic messenger rna
CN116606861A (zh) * 2016-06-07 2023-08-18 摩登纳特斯有限公司 编码vegf-a多肽的经修饰的rna、配制品和关于它们的用途
EP3472352A1 (en) 2016-06-17 2019-04-24 Alexion Pharmaceuticals, Inc. Lysosomal acid lipase deficiency compositions and methods
CA2971303A1 (en) 2016-06-21 2017-12-21 Bamboo Therapeutics, Inc. Optimized mini-dystrophin genes and expression cassettes and their use
PT109480B (pt) 2016-06-22 2020-03-13 Inst Superior Tecnico Polímero de polibenzimidazolo com cadeia espaçadora funcionalizada e seu método de obtenção para remoção de impurezas genotóxicas
CA3034681A1 (en) 2016-06-30 2018-01-04 Arbutus Biopharma Corporation Compositions and methods for delivering messenger rna
US10927383B2 (en) * 2016-06-30 2021-02-23 Ethris Gmbh Cas9 mRNAs
WO2018008319A1 (ja) 2016-07-08 2018-01-11 花王株式会社 核酸試料の調製方法
CN110191954B (zh) * 2016-07-08 2024-05-14 宾夕法尼亚州大学信托人 用于治疗涉及rdh12的病症和疾病的方法和组合物
CA3030534A1 (en) * 2016-07-11 2018-01-18 The National Institute For Biotechnology In The Negev, Ltd. Fusion proteins with extended serum half life
EP4512829A3 (en) 2016-07-14 2025-06-11 Bristol-Myers Squibb Company Antibodies against tim3 and uses thereof
WO2018022511A1 (en) * 2016-07-25 2018-02-01 The Trustees Of The University Of Pennsylvania Compositions comprising a lecithin cholesterol acyltransferase variant and uses thereof
EP3493834A1 (en) 2016-08-07 2019-06-12 Novartis AG Mrna-mediated immunization methods
BR112019002586A2 (pt) 2016-08-09 2019-05-21 Syngenta Participations Ag proteínas inseticidas
US10576167B2 (en) 2016-08-17 2020-03-03 Factor Bioscience Inc. Nucleic acid products and methods of administration thereof
WO2018039557A1 (en) 2016-08-26 2018-03-01 Ngm Biopharmaceuticals, Inc. Methods of treating fibroblast growth factor 19-mediated cancers and tumors
TW202304970A (zh) 2016-08-26 2023-02-01 德商英麥提克生物技術股份有限公司 用於頭頸鱗狀細胞癌和其他癌症免疫治療的新型肽和支架
US11339406B2 (en) 2016-09-12 2022-05-24 Genethon Acid-alpha glucosidase variants and uses thereof
EP3293259A1 (en) * 2016-09-12 2018-03-14 Genethon Acid-alpha glucosidase variants and uses thereof
CN109937253B (zh) 2016-09-14 2023-06-30 摩登纳特斯有限公司 高纯度rna组合物及其制备方法
WO2018067869A1 (en) * 2016-10-07 2018-04-12 Board Of Regents, The University Of Texas System Hla-restricted vgll1 peptides and use thereof
SG11201903018WA (en) 2016-10-07 2019-05-30 Genzyme Corp Early post-transfection isolation of cells (epic) for biologics production
US10633705B2 (en) 2016-10-14 2020-04-28 Alexion Pharmaceuticals, Inc. N-acetyl-alpha-D-glucosaminidase deficiency compositions and methods
KR101837856B1 (ko) 2016-10-18 2018-03-13 단국대학교 산학협력단 뎅기바이러스 혈청형 2 및 3의 메틸트랜스퍼라제 활성을 억제하는 rna 앱타머
JP2020513248A (ja) 2016-10-19 2020-05-14 フロデザイン ソニックス， インク．Ｆｌｏｄｅｓｉｇｎ Ｓｏｎｉｃｓ， Ｉｎｃ． 音響による親和性細胞抽出
MA46584A (fr) 2016-10-21 2019-08-28 Modernatx Inc Vaccin contre le cytomégalovirus humain
CN110402145A (zh) * 2016-10-26 2019-11-01 莫得纳特斯公司 用于增强免疫应答的信使核糖核酸及其使用方法
AR109844A1 (es) * 2016-10-27 2019-01-30 Syngenta Participations Ag Proteínas insecticidas
EP3323827A1 (en) * 2016-11-21 2018-05-23 Christian-Albrechts-Universität zu Kiel Cationic intrinsically disordered antimicrobial peptides
ES2912270T3 (es) * 2016-11-23 2022-05-25 Mayo Found Medical Education & Res Transporte de productos biológicos por medio de partículas
US10558661B2 (en) 2016-11-29 2020-02-11 Sap Se Query plan generation based on table adapter
WO2018102317A1 (en) 2016-11-29 2018-06-07 The Regents Of The University Of California Modulation of p53 for the treatment of cancer
MA50335A (fr) 2016-12-08 2020-08-19 Modernatx Inc Vaccins à acide nucléique contre des virus respiratoires
US11542490B2 (en) 2016-12-08 2023-01-03 CureVac SE RNAs for wound healing
US11384352B2 (en) 2016-12-13 2022-07-12 Modernatx, Inc. RNA affinity purification
CN108531497B (zh) * 2016-12-26 2021-06-15 中国农业科学院兰州兽医研究所 一种重组蛋白p35的制备方法
MX2019007876A (es) 2016-12-30 2019-10-15 Univ Pennsylvania Terapia genetica para tratar fenilcetonuria.
WO2018126084A1 (en) 2016-12-30 2018-07-05 Phaserx, Inc. Branched peg molecules and related compositions and methods
MX2019007873A (es) 2016-12-30 2019-11-18 Univ Pennsylvania Terapia génica para tratar la enfermedad de wilson.
WO2018138376A1 (en) 2017-01-30 2018-08-02 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Novel igfr-like 2 receptor and uses thereof
US20190351039A1 (en) 2017-02-01 2019-11-21 Modernatx, Inc. Immunomodulatory therapeutic mrna compositions encoding activating oncogene mutation peptides
EP3582790A4 (en) 2017-02-16 2020-11-25 ModernaTX, Inc. VERY POWERFUL IMMUNOGENIC COMPOSITIONS
EP3583124A1 (en) 2017-02-17 2019-12-25 Bristol-Myers Squibb Company Antibodies to alpha-synuclein and uses thereof
US10975369B2 (en) * 2017-02-27 2021-04-13 Translate Bio, Inc. Methods for purification of messenger RNA
EP3589290A4 (en) 2017-02-28 2020-12-30 Arcturus Therapeutics, Inc. Translatable molecules and synthesis thereof
JOP20190200A1 (ar) * 2017-02-28 2019-08-27 Univ Pennsylvania تركيبات نافعة في معالجة ضمور العضل النخاعي
CN110337305A (zh) * 2017-02-28 2019-10-15 赛诺菲 治疗性rna
US11266677B2 (en) 2017-03-10 2022-03-08 Memorial Sloan Kettering Cancer Center Methods for treatment or prevention of leukemia
WO2018170172A1 (en) * 2017-03-14 2018-09-20 Baylor College Of Medicine Dominant active yap, a hippo effector, induces chromatin accessiblity and cardiomyocyte renewal
EP3595713A4 (en) 2017-03-15 2021-01-13 ModernaTX, Inc. Respiratory syncytial virus vaccine
US11576961B2 (en) 2017-03-15 2023-02-14 Modernatx, Inc. Broad spectrum influenza virus vaccine
WO2018170270A1 (en) 2017-03-15 2018-09-20 Modernatx, Inc. Varicella zoster virus (vzv) vaccine
US11752206B2 (en) 2017-03-15 2023-09-12 Modernatx, Inc. Herpes simplex virus vaccine
GB201704192D0 (en) * 2017-03-16 2017-05-03 Nightstarx Ltd Treatment of Retinitis Pigmentosa
EP3595676A4 (en) 2017-03-17 2021-05-05 Modernatx, Inc. RNA VACCINES AGAINST ZOONOSES
JOP20190203A1 (ar) 2017-03-30 2019-09-03 Potenza Therapeutics Inc بروتينات رابطة لمولد ضد مضادة لـ tigit وطرق استخدامها
EP4019037A1 (en) * 2017-03-31 2022-06-29 Accanis Biotech F&E GmbH & Co KG Prevention and treatment of non-melanoma skin cancer (nmsc)
US11820999B2 (en) 2017-04-03 2023-11-21 American Gene Technologies International Inc. Compositions and methods for treating phenylketonuria
EP3607074A4 (en) 2017-04-05 2021-07-07 Modernatx, Inc. REDUCTION OR ELIMINATION OF IMMUNE RESPONSES TO NON-INTRAVENOUS THERAPEUTIC PROTEINS, FOR EXAMPLE SUBCUTANEOUSLY
US10640766B2 (en) 2017-04-12 2020-05-05 Tempo Bioscience, Inc. Biosensors for chloride ions
US10571480B2 (en) * 2017-04-12 2020-02-25 Tempo Bioscience, Inc. Biosensors for cellular osmolarity
EA038300B1 (ru) * 2017-04-18 2021-08-06 Юниверсити Оф Флорида Рисерч Фаундейшен, Инкорпорейтед Кднк il-1ra
CN110892062A (zh) 2017-05-05 2020-03-17 佛罗里达大学研究基金会 表达耳畸蛋白的组合物和方法
AU2018265432A1 (en) 2017-05-11 2019-12-19 The Research Foundation For The State University Of New York Compositions and methods for loading extracellular vesicles with chemical and biological agents/molecules
JP7235676B2 (ja) 2017-05-17 2023-03-08 ザ ジェネラル ホスピタル コーポレイション 結節性硬化症の遺伝子治療
US20180338929A1 (en) * 2017-05-23 2018-11-29 Soon Kap Hahn Method and Compounds for Treating Peripheral Neuropathy
CA3064890A1 (en) * 2017-05-26 2018-11-29 The Wistar Institute Of Anatomy And Biology Dtert vaccines and methods of treatment using the same
EP3630200A4 (en) 2017-05-31 2021-02-24 Arcturus Therapeutics, Inc. THERAPEUTICS FOR PHENYLKETONURIA
JP7284101B2 (ja) * 2017-05-31 2023-05-30 ウルトラジェニクス ファーマシューティカル インク． 糖原病ｉｉｉ型のための治療薬
US11015204B2 (en) 2017-05-31 2021-05-25 Arcturus Therapeutics, Inc. Synthesis and structure of high potency RNA therapeutics
WO2018226931A1 (en) * 2017-06-07 2018-12-13 David Weiner Mage-a vaccines and methods of treatment using the same
JP7766393B2 (ja) 2017-06-14 2025-11-10 ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア 眼疾患のための遺伝子療法
MA49395A (fr) 2017-06-14 2020-04-22 Modernatx Inc Polynucléotides codant pour le facteur viii de coagulation
WO2018232357A1 (en) * 2017-06-15 2018-12-20 Modernatx, Inc. Rna formulations
GB201709551D0 (en) * 2017-06-15 2017-08-02 Ucl Business Plc Expression vectors comprising engineered genes
US10034951B1 (en) 2017-06-21 2018-07-31 New England Biolabs, Inc. Use of thermostable RNA polymerases to produce RNAs having reduced immunogenicity
SG10202110492YA (en) 2017-06-22 2021-11-29 Catalyst Biosciences Inc Modified membrane type serine protease 1 (mtsp-1) polypeptides and methods of use
CA3067497A1 (en) * 2017-07-03 2019-01-10 Universite De Strasbourg Mtmr2-s polypeptide for use in the treatment of myopathies
CN107333755B (zh) * 2017-07-04 2021-03-16 南开大学 具有g-四链体结构的水凝胶制备方法及其在杀灭金黄色葡萄球菌和大肠杆菌中的应用
US11628227B2 (en) * 2017-07-05 2023-04-18 Wisconsin Alumni Research Foundation Mineral coated microparticles for gene delivery in chronic wound therapy
WO2019009979A1 (en) * 2017-07-06 2019-01-10 The Medical College Of Wisconsin, Inc. NEW IN VITRO AND IN VIVO ENRICHMENT STRATEGY TARGETING CSH-DERIVED LYMPHOCYTES TRANSDUCED BY A VECTOR FOR DISEASE THERAPY
KR20250007011A (ko) 2017-07-07 2025-01-13 이매틱스 바이오테크놀로지스 게엠베하 Nsclc, sclc 등 폐암 및 기타 암에 대한 면역요법에서의 사용을 위한 신규 펩티드 및 펩티드의 조합
US10800823B2 (en) 2017-07-07 2020-10-13 Immatics Biotechnologies Gmbh Peptides and combination of peptides for use in immunotherapy against lung cancer, including NSCLC, SCLC and other cancers
US11261447B2 (en) 2017-07-13 2022-03-01 Alnylam Pharmaceuticals, Inc. Methods for inhibition of HAO1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
EP3652203B1 (en) 2017-07-14 2025-07-02 The Johns Hopkins University Engineered tsc2
WO2019018765A1 (en) 2017-07-21 2019-01-24 Modernatx, Inc. MODIFIED mRNA ENCODING PROPIONYL-COA-CARBOXYLASE AND USES THEREOF
WO2019023179A1 (en) 2017-07-24 2019-01-31 Modernatx, Inc. MODIFIED mRNA ENCODING GLUCOSE-6-PHOSPHATASE AND USES THEREOF
IL272227B2 (en) 2017-07-27 2025-09-01 iTeos Belgium SA Anti-tigit antibodies
EP4445954A3 (en) * 2017-07-31 2025-01-08 Reflection Biotechnologies Limited Cellular models of and therapies for ocular diseases
US11299515B2 (en) 2017-08-02 2022-04-12 The Regents Of The University Of California Optimized peptides for targeting human nerves and their use in image guided surgery, diagnostics and therapeutic
WO2019036484A1 (en) * 2017-08-15 2019-02-21 The Trustees Of The University Of Pennsylvania COMPOSITIONS AND METHODS FOR THE TREATMENT OF ARGININOSUCCINIC ACIDURIA
EP3668979A4 (en) 2017-08-18 2021-06-02 Modernatx, Inc. METHOD OF HPLC ANALYSIS
EP4397757A3 (en) 2017-08-18 2024-10-23 ModernaTX, Inc. Rna polymerase variants
EP3668977A4 (en) 2017-08-18 2021-04-21 Modernatx, Inc. HPLC ANALYTICAL PROCESSES
HRP20240485T1 (hr) 2017-08-24 2024-07-05 Novo Nordisk A/S Pripravci glp-1 i njihova upotreba
US11744801B2 (en) 2017-08-31 2023-09-05 Modernatx, Inc. Methods of making lipid nanoparticles
AU2018328223A1 (en) 2017-09-05 2020-03-12 GLAdiator Biosciences, Inc. Delivery of payloads to stem cells
US11788093B2 (en) 2017-09-07 2023-10-17 University Of Florida Research Foundation, Inc. Chimeric antigen receptor t-cells expressing interleukin-8 receptor
CA3074839A1 (en) 2017-09-07 2019-03-14 Cue Biopharma, Inc. T-cell modulatory multimeric polypeptide with conjugation sites and methods of use thereof
EP3681514A4 (en) 2017-09-14 2021-07-14 ModernaTX, Inc. RNA VACZINE AGAINST ZIKA VIRUS
KR102709597B1 (ko) * 2017-10-03 2024-09-26 프리베일 테라퓨틱스, 인크. 리소좀 장애를 위한 유전자 요법
AU2018346102B2 (en) 2017-10-03 2023-05-11 Prevail Therapeutics, Inc. Gene therapies for lysosomal disorders
KR102726267B1 (ko) * 2017-10-16 2024-11-11 센트로 데 인베스띠가씨오네스 에너제티까스 메디오암비엔딸레스 와이 테크놀로지까스, 오.에이., 엠.피. 피루베이트 키나제 결핍증을 치료하기 위한 pklr 전달용 렌티바이러스 벡터
EP3697401B1 (en) * 2017-10-18 2025-12-03 Washington University Dominant negative sarm1 molecules as a therapeutic strategy for neurodegenerative diseases or disorders
WO2019089818A1 (en) * 2017-10-31 2019-05-09 Modernatx, Inc. Lipid nanoparticles for delivering modified rna encoding a vegf-a polypeptide
WO2019104160A2 (en) 2017-11-22 2019-05-31 Modernatx, Inc. Polynucleotides encoding phenylalanine hydroxylase for the treatment of phenylketonuria
WO2019104195A1 (en) 2017-11-22 2019-05-31 Modernatx, Inc. Polynucleotides encoding propionyl-coa carboxylase alpha and beta subunits for the treatment of propionic acidemia
EP3713569B1 (en) * 2017-11-22 2024-03-13 University of Pittsburgh- Of the Commonwealth System of Higher Education Therapeutic particle comprising a yap1/wwrt1 inhibiting agent and the glutaminase inhibiting agent 2-cyclopropyl-n-[5-(4-{ [5-(2-phenylacetamido)-1,3,4-thiadiazol-2-yl]amino}piperidin-1-yl)-1,3,4-thiadiazol-2-yl] acetamide and use thereof for treating a pulmonary disease
JP7423522B2 (ja) 2017-11-22 2024-01-29 モダーナティエックス・インコーポレイテッド 尿素サイクル異常症の治療のためのオルニチントランスカルバミラーゼをコードするポリヌクレオチド
US20190248881A1 (en) * 2017-12-04 2019-08-15 Precithera, Inc. TGF-ß RECEPTOR FUSION PROTEINS AND OTHER TGF-ß ANTAGONISTS FOR REDUCING TGF-ß SIGNALING
GB201720224D0 (en) * 2017-12-05 2018-01-17 Royal Holloway & Bedford New College Treatment of muscular dystrophies
JP2021505144A (ja) 2017-12-05 2021-02-18 シンセティック ジェノミクス インコーポレーテッド シグナル伝達タンパク質の遺伝子改変を介した藻類脂質生産性の改善方法
AU2018384824B2 (en) * 2017-12-13 2022-08-04 Inovio Pharmaceuticals, Inc. Cancer vaccines targeting LEMD1 and uses thereof
WO2019118760A1 (en) * 2017-12-13 2019-06-20 Inovio Pharmaceuticals, Inc. Cancer vaccines targeting mesothelin and uses thereof
US10785574B2 (en) 2017-12-14 2020-09-22 Flodesign Sonics, Inc. Acoustic transducer driver and controller
US11802146B2 (en) 2018-01-05 2023-10-31 Modernatx, Inc. Polynucleotides encoding anti-chikungunya virus antibodies
GB201800620D0 (en) * 2018-01-15 2018-02-28 Univ Manchester C3b Binding Polypeptide
MA54676A (fr) 2018-01-29 2021-11-17 Modernatx Inc Vaccins à base d'arn contre le vrs
KR102824021B1 (ko) 2018-01-31 2025-06-24 더 리서치 인스티튜트 앳 네이션와이드 칠드런스 하스피탈 2c형 지대근이영양증에 대한 유전자 치료
CA3091047A1 (en) 2018-02-14 2019-08-22 Yale University Compositions for modulation of a trem or treml protein and methods of use
US11707510B2 (en) * 2018-02-16 2023-07-25 Preclinics Discovery Gmbh Nucleic acid-based botulinum neurotoxin for therapeutic use
WO2019162521A1 (en) * 2018-02-26 2019-08-29 Ablynx Nv Improved nucleotide sequences encoding peptide linkers
US12162994B2 (en) 2018-03-02 2024-12-10 Sigilon Therapeutics, Inc. Biocompatible hydrogel capsules and process for preparing same
US20210002668A1 (en) * 2018-03-07 2021-01-07 Icahn School Of Medicine At Mount Sinai Sphingolipid-metabolizing proteins enhance the efficiency of gene editing in cells
US20240226322A1 (en) * 2018-04-04 2024-07-11 North Carolina State University Fibrin-specific materials and methods of using thereof
UY38160A (es) 2018-04-04 2019-11-29 Sigilon Therapeutics Inc Partículas implantables y métodos relacionados
US12122811B2 (en) 2018-04-06 2024-10-22 Northwestern University BDNF mimetic peptide amphiphiles
US12378576B2 (en) * 2018-04-27 2025-08-05 Spacecraft Seven, Llc Gene therapy for CNS degeneration
MX2020011257A (es) * 2018-04-27 2021-01-15 Krystal Biotech Inc Ácidos nucleicos recombinantes que codifican una o más proteínas cosméticas para usos estéticos.
WO2019210301A1 (en) 2018-04-27 2019-10-31 The Medical College Of Wisconsin, Inc. Use of lentivector-transduced t-rapa cells for amelioration of lysosomal storage disorders
US20210095001A1 (en) 2018-05-02 2021-04-01 The Trustees Of The University Of Pennsylvania Compositions and methods of phospholipase a2 receptor chimeric autoantibody receptor t cells
GB201807831D0 (en) * 2018-05-15 2018-06-27 Univ College Cardiff Consultants Ltd Cancer Vaccine
SG11202011191WA (en) * 2018-05-16 2020-12-30 Spark Therapeutics Inc Codon-optimized acid αlpha-glucosidase expression cassettes and methods of using same
MX2020014119A (es) 2018-06-29 2021-06-18 Res Inst Nationwide Childrens Hospital Productos y métodos de virus adenoasociado recombinante para el tratamiento de la distrofia muscular de cinturas 2a.
CN111073899B (zh) * 2018-10-19 2021-01-01 武汉纽福斯生物科技有限公司 一种编码人nadh脱氢酶亚单位4蛋白的核酸及其应用
US20210244827A1 (en) 2018-06-29 2021-08-12 Icahn School Of Medicine At Mount Sinai Anc80 encoding sphingolipid-metabolizing proteins
CA3103740A1 (en) * 2018-06-29 2020-01-02 Wuhan Neurophth Biotechnology Limited Company Compositions and methods for treating leber's hereditary optic neuropathy
WO2020001657A1 (en) 2018-06-29 2020-01-02 Wuhan Neurophth Biological Technology Limited Company Compositions and methods for treating leber's hereditary optic neuropathy
CN112312921A (zh) 2018-07-02 2021-02-02 美国西门子医学诊断股份有限公司 新型甲状腺过氧化物酶自身抗体免疫测定
KR20210044774A (ko) * 2018-07-04 2021-04-23 사이토이뮨 테라퓨틱스 인코퍼레이티드 Flt3, pd-1 및/또는 pd-l1을 표적으로 하는 면역요법을 위한 조성물 및 방법
CN110699367B (zh) * 2018-07-09 2021-06-11 武汉纽福斯生物科技有限公司 编码人nadh脱氢酶亚单位4蛋白的核酸及其应用
JP2021532082A (ja) 2018-07-11 2021-11-25 オハイオ ユニバーシティ 成長ホルモン作用のペプチドベースの阻害剤及びその使用方法
CA3106838A1 (en) * 2018-07-20 2020-01-23 University Of Utah Research Foundation Gene therapy for macular degeneration
WO2020023390A1 (en) 2018-07-25 2020-01-30 Modernatx, Inc. Mrna based enzyme replacement therapy combined with a pharmacological chaperone for the treatment of lysosomal storage disorders
TWI764022B (zh) * 2018-07-30 2022-05-11 中央研究院 凝聚複合物的治療性奈米粒子及其治療細菌的用途
CN119752801A (zh) * 2018-08-01 2025-04-04 南克维斯特公司 用于免疫疗法的基因修饰的包含归巢受体或细胞因子和嵌合抗原受体的四顺反子系统
CA3109236A1 (en) * 2018-08-13 2020-02-20 Aarhus Universitet Genetically altered lysm receptors with altered agonist specificity and affinity
WO2020041500A1 (en) * 2018-08-21 2020-02-27 Georgia State University Research Foundation, Inc. Treatment of flavivirus infections in humans using mus musculus resistant 2'-5' oligoadenylate synthetase 1b
CA3110103A1 (en) * 2018-08-22 2020-02-27 Blueallele, Llc Methods for delivering gene editing reagents to cells within organs
WO2020041142A1 (en) * 2018-08-23 2020-02-27 Rutgers, The State University Of New Jersey Treating spinal cord injury (sci) and brain injury using gsx1
JP2021534196A (ja) 2018-08-23 2021-12-09 シージェン インコーポレイテッド 抗ｔｉｇｉｔ抗体
WO2020047476A1 (en) * 2018-08-31 2020-03-05 University Of Florida Research Foundation, Incorporated Adeno-associated viral vectors for the treatment of best disease
WO2020047201A1 (en) 2018-09-02 2020-03-05 Modernatx, Inc. Polynucleotides encoding very long-chain acyl-coa dehydrogenase for the treatment of very long-chain acyl-coa dehydrogenase deficiency
CN109385487B (zh) * 2018-09-11 2022-04-01 浙江省食品药品检验研究院 贵细中草药西洋参的重组酶介导扩增恒温检测方法及试剂盒
MA53608A (fr) 2018-09-13 2021-07-21 Modernatx Inc Polynucléotides codant pour les sous-unités e1-alpha, e1-beta et e2 du complexe alpha-cétoacide déshydrogénase à chaîne ramifiée pour le traitement de la leucinose
MA53609A (fr) 2018-09-13 2021-07-21 Modernatx Inc Polynucléotides codant la glucose-6-phosphatase pour le traitement de la glycogénose
US20220401584A1 (en) 2018-09-14 2022-12-22 Modernatx, Inc. Polynucleotides encoding uridine diphosphate glycosyltransferase 1 family, polypeptide a1 for the treatment of crigler-najjar syndrome
JP7344300B2 (ja) 2018-09-18 2023-09-13 ブイエヌブイ ニューコ インク． Ａｒｃベースのカプシドおよびその使用
CN109106948B (zh) * 2018-09-19 2022-03-29 天康制药(苏州)有限公司 一种口蹄疫抗原保护剂及其应用
WO2020061457A1 (en) 2018-09-20 2020-03-26 Modernatx, Inc. Preparation of lipid nanoparticles and methods of administration thereof
CA3113435A1 (en) 2018-09-25 2020-04-02 Emory University Nucleic acids for cell recognition and integration
US20220152225A1 (en) 2018-09-27 2022-05-19 Modernatx, Inc. Polynucleotides encoding arginase 1 for the treatment of arginase deficiency
AU2019355177A1 (en) 2018-10-04 2021-05-06 New England Biolabs, Inc. Methods and compositions for increasing capping efficiency of transcribed RNA
US11072808B2 (en) 2018-10-04 2021-07-27 New England Biolabs, Inc. Methods and compositions for increasing capping efficiency of transcribed RNA
CN113166783B (zh) 2018-10-09 2024-10-11 不列颠哥伦比亚大学 包含无有机溶剂和去污剂的转染活性囊泡的组合物和系统以及与之相关的方法
US12331320B2 (en) 2018-10-10 2025-06-17 The Research Foundation For The State University Of New York Genome edited cancer cell vaccines
CA3116098A1 (en) * 2018-10-12 2020-04-16 Vivet Therapeutics Codon-optimized transgene for the treatment of progressive familiar intrahepatic cholestasis type 3 (pfic3)
KR20210086662A (ko) * 2018-10-29 2021-07-08 오타와 하스피털 리서치 인스티튜트 Aoah를 과발현하는 유전자조작된 중간엽 줄기 세포 및 이의 용도
CN111118016B (zh) 2018-10-30 2022-04-15 上海朗昇生物科技有限公司 治疗视网膜色素变性疾病的基因治疗载体
US20210395751A1 (en) * 2018-10-31 2021-12-23 The University Of Sydney Compositions and methods for treating viral infections
WO2020093018A1 (en) * 2018-11-01 2020-05-07 University Of Florida Research Foundation, Incorporated A codon optimized otoferlin aav dual vector gene therapy
BR112021006074A2 (pt) 2018-11-05 2021-07-20 The University Of North Carolina At Chapel Hill genes e cassetes de expressão fig4 otimizados e seu uso
AU2019375450A1 (en) * 2018-11-07 2021-06-17 Vivet Therapeutics Codon-optimized ABCB11 transgene for the treatment of progressive familial intrahepatic cholestasis type 2 (PFIC2)
US20220016265A1 (en) * 2018-11-09 2022-01-20 Translate Bio, Inc. Messenger rna therapy for treatment of ocular diseases
EP3880229A2 (en) 2018-11-14 2021-09-22 Urovant Sciences GmbH Compositions and methods for the treatment of smooth muscle dysfunction
WO2020117715A1 (en) 2018-12-03 2020-06-11 Board Of Regents, The University Of Texas System Oligo-benzamide analogs and their use in cancer treatment
AR117327A1 (es) 2018-12-20 2021-07-28 23Andme Inc Anticuerpos anti-cd96 y métodos de uso de estos
EP3884057A4 (en) 2018-12-21 2022-09-07 The University of North Carolina at Chapel Hill OPTIMIZED GALC GENES AND EXPRESSION CASSETTE AND THEIR USE
GB201821089D0 (en) * 2018-12-21 2019-02-06 Gyroscope Therapeutics Ltd Codon-optimised complement factor I
CA3124721A1 (en) 2018-12-24 2020-07-02 Xiaoyi Zhou Recombinant human 21g-b7-h3 protein coding gene, recombinant vector, host cell comprising the same, pharmaceutical composition and use thereof
WO2020029521A1 (zh) * 2018-12-25 2020-02-13 深圳晶泰科技有限公司 有机分子的立体异构全集自动化生成方法
US12338450B2 (en) 2019-01-04 2025-06-24 Ultragenyx Pharmaceutical Inc. Gene therapy constructs for treating Wilson disease
WO2020146625A1 (en) * 2019-01-09 2020-07-16 The Johns Hopkins University Engineered tuberous sclerosis complex 2 polypeptides
WO2020150402A2 (en) * 2019-01-15 2020-07-23 Caerus Therapeutics, Corp. Advanced chimeric antigen receptor vectors for targeting solid tumors
EP3911355A4 (en) * 2019-01-15 2022-06-01 Cornell University RECOMBINANT LUBRICINS AND COMPOSITIONS AND METHODS OF USE THEREOF
CA3128384A1 (en) 2019-02-04 2020-08-13 Minerva Biotechnologies Corporation Anti-nme antibody and method of treating cancer or cancer metastasis
US20220118060A1 (en) * 2019-02-04 2022-04-21 The Regents Of The University Of California Exercise-induced circulatory factors for amelioration of cognitive, neurological, and regenerative dysfunction during aging
MX2021009305A (es) * 2019-02-04 2021-11-04 Freeline Therapeutics Ltd Polinucleotidos.
EP3693457A1 (en) * 2019-02-05 2020-08-12 Pharmaq AS Novel fish totivirus
WO2020163743A1 (en) 2019-02-08 2020-08-13 Decibel Therapeutics, Inc. Compositions and methods for treating sensorineural hearing loss using otoferlin dual vector systems
US11351242B1 (en) 2019-02-12 2022-06-07 Modernatx, Inc. HMPV/hPIV3 mRNA vaccine composition
MA55037A (fr) 2019-02-20 2021-12-29 Modernatx Inc Variants d'arn polymérase pour le coiffage co-transcriptionnel
US11851694B1 (en) 2019-02-20 2023-12-26 Modernatx, Inc. High fidelity in vitro transcription
US20220054655A1 (en) * 2019-02-22 2022-02-24 University Of Massachusetts Oxr1 gene therapy
MX2021010356A (es) 2019-02-26 2022-03-04 Res Inst Nationwide Childrens Hospital SUMINISTRO DE ß-SARCOGLICANO MEDIANTE VECTORES DE VIRUS ADENOASOCIADO Y EL TRATAMIENTO DE LA DISTROFIA MUSCULAR.
AU2020232238B2 (en) * 2019-03-01 2025-10-30 Flagship Pioneering Innovations Vi, Llc Polyribonucleotides and cosmetic uses thereof
MX2021011031A (es) 2019-03-11 2021-12-10 Modernatx Inc Proceso de transcripción in vitro en lotes alimentados.
US12070495B2 (en) 2019-03-15 2024-08-27 Modernatx, Inc. HIV RNA vaccines
WO2020198685A1 (en) * 2019-03-27 2020-10-01 Sigilon Therapeutics, Inc. Compositions, devices and methods for treating fabry disease
US20230123802A1 (en) * 2019-03-27 2023-04-20 Sigilon Therapeutics, Inc. Compositions, devices, and methods for factor vii therapy
US10967119B1 (en) 2019-04-01 2021-04-06 Azizi Bilal Wearable medication injecting device
CN109998055B (zh) * 2019-04-09 2022-03-25 黑龙江省科学院大庆分院 一种汉麻籽抗氧化多肽咀嚼片及其制备方法
WO2020214694A1 (en) * 2019-04-15 2020-10-22 The Regents Of The University Of California Treatment for restoring ureagenesis in carbamoyl phosphate synthetase 1 deficiency
US12357695B2 (en) 2019-04-17 2025-07-15 Aadigen, Llc Peptides and nanoparticles for intracellular delivery of molecules
JP2022530095A (ja) * 2019-04-24 2022-06-27 ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア レット症候群の治療に有用な組成物
WO2020222858A1 (en) * 2019-04-27 2020-11-05 Ocugen, Inc. Adeno-associated virus vector mediated gene therapy for ophthalmic diseases
BR112021021908A2 (pt) 2019-05-03 2022-02-01 Univ Pennsylvania Composições úteis no tratamento da leucodistrofia metacromática
EP3965797A1 (en) 2019-05-08 2022-03-16 AstraZeneca AB Compositions for skin and wounds and methods of use thereof
WO2020227542A1 (en) * 2019-05-08 2020-11-12 The Regents Of The University Of California A method to prevent the myelin abnormalites associated with arginase deficiency
CN114072514A (zh) * 2019-05-14 2022-02-18 杜克大学 用于治疗atp酶介导的疾病的组合物和方法
EP3973291A1 (en) * 2019-05-21 2022-03-30 Regeneron Pharmaceuticals, Inc. Methods for identifying and quantitating host cell protein
BR112021024124A2 (pt) * 2019-05-31 2022-01-11 American Gene Tech Int Inc Expressão otimizada de fenilalanina hidroxilase
JP2022536364A (ja) 2019-06-13 2022-08-15 ザ ジェネラル ホスピタル コーポレイション 操作されたヒト内在性ウイルス様粒子および細胞への送達のためのその使用方法
EP3997241A4 (en) * 2019-06-20 2023-09-27 The Trustees of The University of Pennsylvania Compositions and methods for treatment of maple syrup urine disease
CN110256578B (zh) * 2019-06-24 2021-04-23 王跃驹 植物生产人霍乱毒素b亚基(ctb)与胰岛素原的融合蛋白速效口服降糖胶囊的应用
CN110327307B (zh) * 2019-06-26 2020-06-23 浙江大学 一种丝素载药纳米微囊的制备方法及产品
US20210052776A1 (en) 2019-07-02 2021-02-25 Nevin Witman Mesenchymal stem cells or stromal cells harboring modified rnas encoding vegf and bmp polypeptides
CN114450265B (zh) 2019-07-03 2024-12-24 菲克特生物科学股份有限公司 阳离子脂质及其用途
US20220257725A1 (en) * 2019-07-11 2022-08-18 University Of Utah Research Foundation Compositions and methods for treating peroxisomal biogenesis disorders
US11377655B2 (en) 2019-07-16 2022-07-05 Pacific Biosciences Of California, Inc. Synthetic nucleic acids having non-natural structures
US10501404B1 (en) 2019-07-30 2019-12-10 Factor Bioscience Inc. Cationic lipids and transfection methods
CN120400170A (zh) 2019-08-21 2025-08-01 全国儿童医院研究所 Α-肌聚糖的腺相关病毒载体递送和肌营养不良症的治疗
US11644463B2 (en) * 2019-08-30 2023-05-09 Euroimmun Medizinische Labordiagnostika Ag Detection of an autoantibody
US20230172858A1 (en) 2019-08-30 2023-06-08 Glaxosmithkline Biologicals Sa Jet mixing lipid nanoparticle manufacturing process
EP4025686A4 (en) * 2019-09-03 2023-09-13 Myeloid Therapeutics, Inc. Methods and compositions for genomic integration
CA3153980A1 (en) * 2019-09-13 2021-03-18 Regeneron Pharmaceuticals, Inc. Transcription modulation in animals using crispr/cas systems delivered by lipid nanoparticles
WO2021067389A1 (en) 2019-09-30 2021-04-08 Bioverativ Therapeutics Inc. Lentiviral vector formulations
WO2021067687A1 (en) * 2019-10-03 2021-04-08 Board Of Regents, The University Of Texas System Vcx/y peptides and use thereof
JP2022552378A (ja) * 2019-10-15 2022-12-15 モデルナティエックス インコーポレイテッド パーキンソン病を治療するための顆粒球マクロファージコロニー刺激因子をコードするｍＲＮＡ
CA3158516A1 (en) * 2019-10-22 2021-04-29 Applied Genetic Technologies Corporation Adeno-associated virus (aav) systems for treatment of progranulin associated neurodegeneative diseases or disorders
CN110684751B (zh) * 2019-10-23 2021-06-25 江南大学 一种催化能力提高的淀粉分支酶突变体
IL292372A (en) * 2019-10-23 2022-06-01 Univ Pennsylvania Compositions for drg-specific reduction of transgene expression
EP4073231A4 (en) * 2019-10-30 2024-06-05 Amicus Therapeutics, Inc. RECOMBINANT CDKL5 PROTEINS, GENE THERAPY AND METHODS OF PRODUCTION
CN110669104B (zh) * 2019-10-30 2021-11-05 上海交通大学 一组来源于人外周血单核细胞的标志物及其应用
WO2021092440A1 (en) * 2019-11-07 2021-05-14 Icahn School Of Medicine At Mount Sinai Synthetic modified rna and uses thereof
WO2021097088A1 (en) * 2019-11-12 2021-05-20 University Of Virginia Patent Foundation Optidicer construct for age-related macular degeneration
CA3158582A1 (en) * 2019-11-22 2021-05-27 Critical Outcome Technologies Inc. Peptides, compounds, compositions and methods for inhibiting sox9 dimerization
BR112022010680A2 (pt) 2019-12-03 2022-08-16 Evotec Int Gmbh Proteínas de ligação ao antígeno associado ao interferon e uso das mesmas
CN113025633B (zh) * 2019-12-09 2024-08-27 武汉纽福斯生物科技有限公司 编码人nadh脱氢酶亚单位1蛋白的核酸及其应用
US11904006B2 (en) 2019-12-11 2024-02-20 University Of Iowa Research Foundation Poly(diaminosulfide) particle-based vaccine
CA3161668A1 (en) 2019-12-20 2021-06-24 Nammi Therapeutics, Inc. Formulated and/or co-formulated liposome compositions containing toll-like receptor ("tlr") agonist prodrugs useful in the treatment of cancer and methods thereof
JP7500193B2 (ja) * 2019-12-27 2024-06-17 小林製薬株式会社 乳化組成物
CN113115821B (zh) * 2019-12-30 2024-07-05 丰益(上海)生物技术研发中心有限公司 含多肽的结构化乳液
CN111004787B (zh) * 2020-01-06 2022-05-10 江南大学 一种链霉菌磷脂酶d突变体、改造方法及其应用
US20230054941A1 (en) * 2020-01-13 2023-02-23 University Of Kentucky Research Foundation Inhibition of dennd5b expression for treating hepatic steatosis
CN111166884B (zh) * 2020-01-15 2021-12-03 广州中医药大学第一附属医院 Foxf1基因在制备用于骨质疏松症药物中的应用
KR102114880B1 (ko) * 2020-01-15 2020-05-26 서울대학교병원 코돈 최적화된 TIF1γ 폴리뉴클레오티드를 포함하는 재조합 벡터 및 이의 용도
IL294708A (en) * 2020-01-17 2022-09-01 Univ New York Adeno-associated viral vector, compositions, methods of promoting muscle regeneration, and treatment methods
WO2021151001A1 (en) 2020-01-22 2021-07-29 Outpace Bio, Inc. Chimeric polypeptides
US11230699B2 (en) 2020-01-28 2022-01-25 Immunitybio, Inc. Chimeric antigen receptor-modified NK-92 cells targeting EGFR super-family receptors
US12194089B2 (en) 2020-02-04 2025-01-14 CureVac SE Coronavirus vaccine
US20230235008A1 (en) * 2020-02-14 2023-07-27 H. Lee Moffitt Cancer Center And Research Institute, Inc. Novel t cell receptors (tcrs) that react to neoantigens
MX2022009844A (es) 2020-02-18 2022-09-05 Novo Nordisk As Composiciones y usos del peptido similar al glucagon-1 (glp-1).
AU2021223138A1 (en) * 2020-02-21 2022-09-29 Sky Perfect International Limited Methods and compositions for modulating arginine levels in immune cells
US12497612B2 (en) 2020-03-09 2025-12-16 University Of Massachusetts Gene replacement therapy for FOXG1 syndrome
US20230150926A1 (en) 2020-03-17 2023-05-18 Genevant Sciences Gmbh Cationic lipids for lipid nanoparticle delivery of therapeutics to hepatic stellate cells
JP2021147353A (ja) * 2020-03-19 2021-09-27 国立大学法人信州大学 組成物、脂質粒子製造用キット、物質送達方法及び検出方法
IL295741A (en) 2020-04-01 2022-10-01 Univ Florida Dual aav-myo7a vectors with improved safety for the treatment of ush1b
WO2021207077A1 (en) * 2020-04-06 2021-10-14 Homology Medicines, Inc. Adeno-associated virus compositions for ids gene transfer and methods of use thereof
EP4135777A4 (en) 2020-04-14 2025-03-12 University Of Florida Research Foundation, Incorporated AAV-BASED GENE THERAPIES FOR THE TREATMENT OF AUTOIMMUNE DISEASES
IL297635A (en) * 2020-04-27 2022-12-01 Univ Pennsylvania Compositions useful in treatment of cdkl5 deficiency disorder (cdd)
CN111665361B (zh) * 2020-04-29 2023-02-28 中南林业科技大学 一种溶酶体标记磁性荧光淀粉纳米颗粒及其制备方法
WO2021222801A2 (en) * 2020-05-01 2021-11-04 Arcturus Therapeutics, Inc. Nucleic acids and methods of treatment for cystic fibrosis
CN116234902A (zh) * 2020-05-04 2023-06-06 利兰·斯坦福青年大学托管委员会 用于激活和沉默基因表达的效应物结构域的生成、鉴定和表征的组合物、系统和方法
US20240043835A1 (en) * 2020-05-11 2024-02-08 The Board Of Trustees Of The Leland Stanford Junior University Systems and Methods for Enhancing Gene Expression
AU2021271317A1 (en) 2020-05-15 2023-01-19 Crispr Therapeutics Ag Messenger RNA encoding Cas9 for use in genome-editing systems
US11129892B1 (en) 2020-05-18 2021-09-28 Vnv Newco Inc. Vaccine compositions comprising endogenous Gag polypeptides
CN116157140A (zh) * 2020-05-29 2023-05-23 贝索制药有限责任公司 具有肾酶促效剂活性的稳定胜肽
JP2023527875A (ja) 2020-06-01 2023-06-30 モダーナティエックス・インコーポレイテッド フェニルアラニンヒドロキシラーゼバリアント及びその使用
CA3181655A1 (en) 2020-06-08 2021-12-16 Minerva Biotechnologies Corporation Anti-nme antibody and method of treating cancer or cancer metastasis
JP2023529457A (ja) * 2020-06-09 2023-07-10 ロシュ イノベーション センター コペンハーゲン エーエス 治療用ポリヌクレオチドに使用するためのグアノシン類似体
CN116194755A (zh) * 2020-06-23 2023-05-30 总医院公司 隧道纳米管细胞及其用于递送生物分子的方法
US12173307B2 (en) 2020-06-24 2024-12-24 Bioverativ Therapeutics Inc. Methods for the purification of viral vectors
US20230242678A1 (en) 2020-06-26 2023-08-03 Minerva Biotechnologies Corporation Anti-nme antibody and method of treating cancer or cancer metastasis
US20240350492A1 (en) 2020-07-10 2024-10-24 Ting Therapeutics Llc Methods for the Prevention and Treatment of Hearing Loss
JP2023536067A (ja) * 2020-07-23 2023-08-23 ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル 最適化されたｓｌｃ１３ａ５遺伝子および発現カセットならびにそれらの使用
WO2022020800A2 (en) 2020-07-24 2022-01-27 The General Hospital Corporation Enhanced virus-like particles and methods of use thereof for delivery to cells
EP4189095A1 (en) * 2020-07-27 2023-06-07 Voyager Therapeutics, Inc. Compositions and methods for the treatment of neurological disorders related to glucosylceramidase beta deficiency
MX2023001137A (es) * 2020-07-29 2023-02-22 Freeline Therapeutics Ltd Beta-glucocerebrosidasa mutada con estabilidad mejorada.
EP4188404A4 (en) 2020-07-29 2025-02-26 The Board Of Regents Of The University Of Texas System TRANSGENIC CASSETTES, AAV VECTORS AND AAV VIRUS VECTORS FOR THE EXPRESSION OF HUMAN CODON-OPTIMIZED CSTB
BR112023001788A2 (pt) * 2020-08-03 2023-02-23 Prevail Therapeutics Inc Vetores aav que codificam parkina e usos da mesma
CN114053165B (zh) * 2020-08-06 2023-10-20 大江生医股份有限公司 生物活性物质用于制备改善皮肤状态的组合物的用途
TWI784298B (zh) * 2020-08-06 2022-11-21 大江生醫股份有限公司 生物活性物質用於製備促進肌膚膠原蛋白質生成及提升肌膚膠原蛋白質密度的組合物的用途
US11406703B2 (en) 2020-08-25 2022-08-09 Modernatx, Inc. Human cytomegalovirus vaccine
WO2022046840A1 (en) * 2020-08-26 2022-03-03 Arizona Board Of Regents On Behalf Of The University Of Arizona Hybrid allosteric receptor-engineered stem cells
JP2023542867A (ja) 2020-09-11 2023-10-12 グリンプス バイオ， インコーポレイテッド 疾患の検出／診断、病期分類、モニタリング及び処置のための生体外でのプロテアーゼ活性検出
WO2022066757A1 (en) * 2020-09-23 2022-03-31 Myeloid Therapeutics, Inc. Improved methods and compositions for expression of nucleic acids in cells
CN112063625A (zh) * 2020-09-24 2020-12-11 武汉纽福斯生物科技有限公司 编码arl2bp的核酸及其应用
CA3197178A1 (en) * 2020-09-29 2022-04-07 NeuExcell Therapeutics Inc. Neurod1 combination vector
AU2021360494A1 (en) 2020-10-14 2023-05-18 George Mason Research Foundation, Inc. Ionizable lipids and methods of manufacture and use thereof
JP2023554540A (ja) * 2020-10-28 2023-12-27 ザ チルドレンズ メディカル センター コーポレーション 切断型修飾組換えａｄａｍｔｓ１３およびその使用
US11771652B2 (en) 2020-11-06 2023-10-03 Sanofi Lipid nanoparticles for delivering mRNA vaccines
US20220145302A1 (en) * 2020-11-09 2022-05-12 Battle Biotech, LLC Targets and methods for treating epstein-barr virus mediated neurodegeneration
US20230405109A1 (en) * 2020-11-11 2023-12-21 City Of Hope Nucleic acids, proteins, and vaccines of sars-cov-2
CA3199784A1 (en) 2020-11-13 2022-05-19 Modernatx, Inc. Polynucleotides encoding cystic fibrosis transmembrane conductance regulator for the treatment of cystic fibrosis
CN112402592B (zh) * 2020-12-04 2023-06-02 中国人民解放军陆军军医大学 Spink7蛋白在制备促进过度炎症创面愈合的药物中的应用
CN112480242B (zh) * 2020-12-04 2023-06-06 中国人民解放军陆军军医大学 Spink7蛋白在制备预防和/或治疗溃疡性结肠炎的药物中的应用
CN112552375B (zh) * 2020-12-11 2022-12-23 中国水产科学研究院南海水产研究所 一种罗非鱼副产物抗菌肽及其筛选方法和应用
CN112592902B (zh) * 2020-12-16 2022-03-29 熊猫乳品集团股份有限公司 一种生物活性肽aseppvldvkrpflc及其制备方法和应用
AU2021403156A1 (en) 2020-12-18 2023-07-13 Genevant Sciences Gmbh Peg lipids and lipid nanoparticles
US11596589B2 (en) 2020-12-19 2023-03-07 Purvala Bioscience, Inc. Compositions and method of use for hair straightening and shaping
US11918643B2 (en) 2020-12-22 2024-03-05 CureVac SE RNA vaccine against SARS-CoV-2 variants
EP4271390A4 (en) * 2020-12-30 2025-12-10 Mayo Found Medical Education & Res DELETION-REPLACEMENT GENE THERAPY
US12329811B2 (en) 2021-01-11 2025-06-17 Modernatx, Inc. Seasonal RNA influenza virus vaccines
US20240301380A1 (en) * 2021-01-14 2024-09-12 Spark Therapeutics, Inc. Compositions and Methods for Treating Fabry Disease
EP4277667A1 (en) 2021-01-14 2023-11-22 Alume Biosciences, Inc. Methods and compositions for visualizing a ureter in a surgical procedure
WO2022156939A1 (en) * 2021-01-22 2022-07-28 HigherSteaks Limited Products for cell conversion
CN112725346A (zh) * 2021-01-22 2021-04-30 青岛大学 一种增加尿酸排泄的修饰mRNA序列及其应用
WO2022165027A2 (en) * 2021-01-27 2022-08-04 Spark Therapeutics, Inc. Compositions and methods for treating hereditary angioedema
US20240123040A1 (en) * 2021-02-05 2024-04-18 Sigilon Therapeutics, Inc. Compositions, devices and methods for treating mps vi disease
US20240158833A1 (en) * 2021-02-19 2024-05-16 New England Biolabs, Inc. Compositions and Methods for Labeling Modified Nucleotides in Nucleic Acids
US12144827B2 (en) 2021-02-25 2024-11-19 Lyell Immunopharma, Inc. ROR1 targeting chimeric antigen receptor
KR20230150834A (ko) * 2021-02-25 2023-10-31 라이엘 이뮤노파마, 인크. Ap-1 전사 인자를 인코딩하는 코돈-최적화된 뉴클레오티드 서열
MX2023010461A (es) * 2021-03-08 2023-09-14 Eyegene Inc Composicion para la entrega in vivo de arn y metodo de preparacion para la misma.
CN117295530A (zh) * 2021-03-19 2023-12-26 世代生物公司 非病毒dna载体及其用于表达pfic治疗剂的用途
US20240123087A1 (en) * 2021-03-19 2024-04-18 Recode Therapeutics, Inc. Polynucleotide compositions, related formulations, and methods of use thereof
EP4313110A4 (en) * 2021-03-22 2025-06-25 The Johns Hopkins University K-ras inhibitor
KR20230175196A (ko) 2021-03-23 2023-12-29 리코드 테라퓨틱스, 인크. 폴리뉴클레오티드 조성물, 관련된 제제, 및 이의 사용 방법
WO2022204371A1 (en) 2021-03-24 2022-09-29 Modernatx, Inc. Lipid nanoparticles containing polynucleotides encoding glucose-6-phosphatase and uses thereof
WO2022204390A1 (en) 2021-03-24 2022-09-29 Modernatx, Inc. Lipid nanoparticles containing polynucleotides encoding phenylalanine hydroxylase and uses thereof
WO2022204380A1 (en) 2021-03-24 2022-09-29 Modernatx, Inc. Lipid nanoparticles containing polynucleotides encoding propionyl-coa carboxylase alpha and beta subunits and uses thereof
US20240226025A1 (en) 2021-03-24 2024-07-11 Modernatx, Inc. Polynucleotides encoding methylmalonyl-coa mutase for the treatment of methylmalonic acidemia
WO2022204370A1 (en) 2021-03-24 2022-09-29 Modernatx, Inc. Lipid nanoparticles and polynucleotides encoding ornithine transcarbamylase for the treatment of ornithine transcarbamylase deficiency
US12104181B2 (en) * 2021-03-31 2024-10-01 The Board Of Regents Of The University Of Texas System Compositions and methods for treating viral infections targeting TRIM7
WO2022217037A1 (en) * 2021-04-09 2022-10-13 Board Of Regents, The University Of Texas System Compositions and methods for treatment of chronic lung diseases
CN117178057A (zh) * 2021-04-12 2023-12-05 加利福尼亚大学董事会 用于致心律失常性右心室心肌病的基因治疗
CN115385998B (zh) * 2021-04-13 2025-08-05 杭州先为达生物科技股份有限公司 稳定的iii型干扰素蛋白及其融合蛋白
WO2022226020A2 (en) * 2021-04-20 2022-10-27 Walking Fish Therapeutics Engineering b cell-based protein factories to treat serious diseases
CN115025247A (zh) * 2021-04-23 2022-09-09 上海交通大学医学院 包载促血小板生成素mRNA的组合物及其用途
EP4082560B1 (en) * 2021-04-27 2025-02-26 Academia Sinica Prap1 polypeptide for use in treating hypertriglyceridemia
EP4085932A1 (en) * 2021-05-03 2022-11-09 H.M.Z. Privatstiftung Stabilized, modified rna for use in the treatment of a disease associated with the cystic fibrosis transmembrane conductance regulator (cftr) gene
EP4333903A4 (en) * 2021-05-03 2025-03-19 North Carolina State University COMPOSITIONS AND METHODS RELATED TO THE TREATMENT OF OPHTHALMIC DISEASES IN HORSES
US20220363937A1 (en) 2021-05-14 2022-11-17 Armstrong World Industries, Inc. Stabilization of antimicrobial coatings
WO2022251096A1 (en) * 2021-05-23 2022-12-01 Oregon Health & Science University Promoter sequence and related products and uses thereof
WO2022251644A1 (en) 2021-05-28 2022-12-01 Lyell Immunopharma, Inc. Nr4a3-deficient immune cells and uses thereof
US20230052243A1 (en) 2021-06-02 2023-02-16 Lyell Immunopharma, Inc. Nr4a-deficient cells expressing c-jun and uses thereof
WO2022271776A1 (en) 2021-06-22 2022-12-29 Modernatx, Inc. Polynucleotides encoding uridine diphosphate glycosyltransferase 1 family, polypeptide a1 for the treatment of crigler-najjar syndrome
CN113577303B (zh) * 2021-07-05 2023-06-02 四川大学 三分枝rgd修饰的脑胶质瘤靶向脂质材料的制备和应用
WO2023288325A2 (en) * 2021-07-16 2023-01-19 Ptc Therapeutics Inc. Recombinant reelin gene therapy
US20230280334A1 (en) * 2021-07-30 2023-09-07 Whitehead Institute For Biomedical Research Cdc20 variants resistant to anti-mitotic drugs and related methods and compositions
AU2022327172A1 (en) * 2021-08-11 2024-01-18 The Trustees Of Indiana University Epigenetic modulators for tissue reprogramming
EP4392570A4 (en) * 2021-08-25 2025-07-16 Canbridge Pharmaceuticals Inc AAV PARTICLES COMPRISING A LIVER-TROPIC CAPSID PROTEIN AND AN ACID ALPHA-GLUCOSIDASE (GAA) AND THEIR USE FOR TREATING POMPE DISEASE
EP4405469A4 (en) * 2021-09-24 2025-09-10 Univ Pennsylvania COMPOSITIONS FOR THE TREATMENT OF CHARCOT-MARIE-TOOTH DISEASE
EP4408482A4 (en) * 2021-09-29 2025-11-12 Sirt6 Ltd METHOD OF TREATING A DISEASE
EP4408871A1 (en) 2021-10-01 2024-08-07 ModernaTX, Inc. Polynucleotides encoding relaxin for the treatment of fibrosis and/or cardiovascular disease
US20240382528A1 (en) * 2021-10-05 2024-11-21 The Board Of Trustees Of The Leland Stanford Junior University Treatment of polycythemia vera via crispr/aav6 genome editing
WO2023060126A1 (en) * 2021-10-06 2023-04-13 Dana-Farber Cancer Institute, Inc. Engineered cytokine receptors for tunable adoptive cell therapy
WO2023061985A2 (en) 2021-10-12 2023-04-20 Modernatx, Inc. Compositions comprising modified rna encoding vegf-a and methods of use
EP4219726A1 (en) 2021-10-15 2023-08-02 Research Institute at Nationwide Children's Hospital Self-complementary adeno-associated virus vector and its use in treatment of muscular dystrophy
CA3235208A1 (en) * 2021-10-18 2023-04-27 Logicbio Therapeutics, Inc. Gene therapy for the treatment of ht1
JP2024540170A (ja) 2021-11-01 2024-10-31 モデルナティエックス インコーポレイテッド インテグリンベータ－６をコードするポリヌクレオチド及びその使用方法
US12371666B2 (en) * 2021-11-08 2025-07-29 Boston Medical Center Corporation Nucleoside modified mRNA and uses thereof
WO2023086830A1 (en) * 2021-11-09 2023-05-19 The Trustees Of The University Of Pennsylvania Intraspinal delivery of therapeutic agents
WO2023084013A1 (en) 2021-11-12 2023-05-19 Modernatx, Inc. Compositions comprising modified rna encoding vegf-a and methods of use
WO2023091907A1 (en) * 2021-11-16 2023-05-25 Mayo Foundation For Medical Education And Research Methods and materials for assessing and treating neurologic autoimmune disorders and/or cancer
WO2023122632A1 (en) * 2021-12-21 2023-06-29 Sri International Dual targeting for cell-specific delivery to the central nervous system
WO2023133575A2 (en) * 2022-01-10 2023-07-13 Mahana Therapeutics, Inc. Methods and systems for treating chronic itch conditions using digital therapeutics in combination with other therapies
WO2023141376A2 (en) * 2022-01-20 2023-07-27 Mahana Therapeutics, Inc. Methods and systems for treating respiratory conditions using digital therapeutics in combination with other therapies
ES3017428T3 (en) 2022-01-31 2025-05-12 Genevant Sciences Gmbh Ionizable cationic lipids for lipid nanoparticles
CN114533569B (zh) * 2022-02-16 2023-08-25 杭州诺莘科技有限责任公司 适用于眼部皮肤的细胞穿膜肽/磷脂聚合物修饰的脂质体乳液及其制备和应用
TW202345864A (zh) 2022-02-18 2023-12-01 美商現代公司 編碼檢查點癌症疫苗之ｍＲＮＡ及其用途
CA3245352A1 (en) * 2022-03-04 2023-09-14 Proof Diagnostics, Inc. METHODS AND COMPONENTS FOR DIAGNOSING DISEASES
US20250221931A1 (en) 2022-03-25 2025-07-10 Modernatx, Inc. Polynucleotides encoding fanconi anemia, complementation group proteins for the treatment of fanconi anemia
CN119654166A (zh) 2022-04-01 2025-03-18 内诺维什疗法股份有限公司 mRNA递送方法及其组合物
WO2023196399A1 (en) 2022-04-06 2023-10-12 Modernatx, Inc. Lipid nanoparticles and polynucleotides encoding argininosuccinate lyase for the treatment of argininosuccinic aciduria
AU2023249274A1 (en) * 2022-04-07 2024-10-24 Aleta Biotherapeutics Inc. Compositions and methods for treatment of cancer
WO2023212654A2 (en) * 2022-04-27 2023-11-02 The Regents Of The University Of Colorado A Body Corporate Non-endogenous protein production in plant systems
WO2023218278A1 (en) 2022-05-12 2023-11-16 Urovant Sciences Gmbh Long-term gene therapy for overactive bladder
WO2023220428A1 (en) * 2022-05-12 2023-11-16 Wave Life Sciences Ltd. Compositions for editing ass1 transcripts and methods thereof
JP2025515206A (ja) 2022-05-13 2025-05-13 上海瑞宏迪医薬有限公司 Ｕｔｒを含む核酸構築物及びその使用
EP4525892A1 (en) 2022-05-19 2025-03-26 Lyell Immunopharma, Inc. Polynucleotides targeting nr4a3 and uses thereof
WO2023230003A1 (en) * 2022-05-23 2023-11-30 Yale University Compositions and methods for treating liver disease
CN114920806B (zh) * 2022-06-07 2023-09-12 中南大学 多肽及其抗体、以及检测它们的试剂在制备鼻咽癌诊断、预后或治疗制剂中的应用
PT118087A (pt) 2022-07-06 2024-01-08 I3S Instituto De Investig E Inovacao Em Saude Associacao Supressores de ttl e mcak para uso no tratamento do cancro através da sensibilização à resposta ao taxol
CN117264096A (zh) * 2022-07-21 2023-12-22 杭州诺莘科技有限责任公司 一种超分子聚集体及其制备方法和应用
WO2024026336A2 (en) * 2022-07-26 2024-02-01 The Board Of Trustees Of The Leland Stanford Junior University Methods and reagents for detection, quantitation, and genotyping of epstein-barr virus
WO2024026295A1 (en) * 2022-07-27 2024-02-01 Aera Therapeutics, Inc. Endogenous gag-based and pnma family capsids and uses thereof
CN119895032A (zh) * 2022-07-29 2025-04-25 阿迪塞特治疗公司 针对cd70的亲和结合实体及其使用方法
CN119836437A (zh) * 2022-08-19 2025-04-15 舒泰神(加州)生物科技有限公司 特异性识别程序性细胞死亡1配体1的抗体及其用途
EP4327829A1 (en) 2022-08-26 2024-02-28 Ethris GmbH Stabilization of lipid or lipidoid nanoparticle suspensions
EP4577243A1 (en) 2022-08-26 2025-07-02 Ethris GmbH Stable lipid or lipidoid nanoparticle suspensions
AU2023274159A1 (en) * 2022-09-07 2024-03-21 Eyegene Inc. COMPOSITION FOR IN-VIVO DELIVERING mRNA CONTAINING MODIFIED NUCLEOTIDE
KR102785258B1 (ko) * 2022-09-07 2025-03-26 아이진 주식회사 변형핵산 함유 mRNA의 체내 전달용 조성물
TW202426652A (zh) * 2022-09-14 2024-07-01 美商奧伊斯特普安生物製藥公司 編碼氧化還原酶之aav載體及其用途
WO2024091694A1 (en) * 2022-10-28 2024-05-02 Mary Hitchcock Memorial Hospital, For Itself And On Behalf Of Dartmouth-Hitchcock Clinic Chimeric human receptor for pathogenic viruses
JP2025537125A (ja) * 2022-11-01 2025-11-14 プリベイル・セラピューティクス・インコーポレイテッド フリードライヒ運動失調症の治療のための組成物及び方法
WO2024097737A1 (en) * 2022-11-01 2024-05-10 Ohio State Innovation Foundation Gene therapy for bves-related disorders
EP4630033A1 (en) * 2022-12-09 2025-10-15 Institut National de la Santé et de la Recherche Médicale Novel human antiviral genes related to the eleos and lamassu prokaryotic systems
WO2024130158A1 (en) 2022-12-16 2024-06-20 Modernatx, Inc. Lipid nanoparticles and polynucleotides encoding extended serum half-life interleukin-22 for the treatment of metabolic disease
KR20250133812A (ko) * 2022-12-16 2025-09-08 더 클리브랜드 클리닉 파운데이션 Sfts 바이러스 백신
EP4410316A1 (en) * 2023-02-01 2024-08-07 4basebio UK Ltd Nanoparticles for delivery of nucleic acid cargos
EP4410828A1 (en) 2023-02-02 2024-08-07 Eberhard-Karls-Universität Tübingen Oligonucleotide encoding a tissue inhibitor of metalloproteases protein for medical use in mammals
WO2024182301A2 (en) 2023-02-27 2024-09-06 Modernatx, Inc. Lipid nanoparticles and polynucleotides encoding galactose-1-phosphate uridylyltransferase (galt) for the treatment of galactosemia
WO2024193638A1 (en) * 2023-03-22 2024-09-26 Skyline Therapeutics (Shanghai) Co., Ltd. Recombinant aav for the gene therapy of wilson disease
EP4434534A1 (en) 2023-03-22 2024-09-25 ADvantage Therapeutics, Inc. Klotho mrna
WO2024206329A1 (en) 2023-03-27 2024-10-03 Modernatx, Inc. Nucleic acid molecules encoding bi-specific secreted engagers and uses thereof
WO2024220378A2 (en) * 2023-04-17 2024-10-24 University Of Massachusetts Raav vector for the treatment of cox20 deficiency
WO2024226729A2 (en) * 2023-04-26 2024-10-31 Astellas Gene Therapies, Inc. Compositions and methods for opa1 gene therapy
WO2024223948A1 (en) * 2023-04-28 2024-10-31 Ospedale San Raffaele S.R.L. Vector production
WO2024227231A1 (en) * 2023-05-03 2024-11-07 Monash University Nampt fusion proteins
WO2024229321A1 (en) 2023-05-03 2024-11-07 Modernatx, Inc. Polynucleotides encoding cystic fibrosis transmembrane conductance regulator for the treatment of cystic fibrosis
WO2024236504A1 (en) * 2023-05-15 2024-11-21 Takeda Pharmaceutical Company Limited Sequences and methods for delivery of dna and rna
WO2024240962A1 (en) * 2023-05-25 2024-11-28 Ethris Gmbh Gm-csf-encoding nucleic acids, pharmaceutical compositions, methods and uses thereof
CN119264236A (zh) * 2023-07-05 2025-01-07 中国医学科学院药物研究所 一种角蛋白cf2、制法和其药物组合物与用途
CN117069821B (zh) * 2023-07-14 2024-07-19 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） 靶向人pkm1蛋白的nudt13多肽及其在制备药物中的应用
CN119320441A (zh) * 2023-07-17 2025-01-17 中国医学科学院药物研究所 一种角蛋白cf5、制法和其药物组合物与用途
WO2025045767A1 (en) 2023-08-25 2025-03-06 Ethris Gmbh Stabilized lipid and lipidoid nanoparticle formulations with specific surfactant properties for enhanced pharmaceutical applications
WO2025052278A1 (en) 2023-09-05 2025-03-13 Genevant Sciences Gmbh Pyrrolidine based cationic lipids for lipid nanoparticle delivery of therapeutics to hepatic stellate cells
WO2025072675A1 (en) * 2023-09-29 2025-04-03 Siemens Healthcare Diagnostics Inc. COMPOSITIONS AND METHODS FOR REVERSE TRANSCRIBING MATURE miRNA FOR qPCR
CN119841928A (zh) * 2023-10-18 2025-04-18 中国医学科学院药物研究所 一种角蛋白cf6、制法和其药物组合物与用途
US12364773B2 (en) 2023-12-01 2025-07-22 Recode Therapeutics, Inc. Lipid nanoparticle compositions and uses thereof
WO2025122940A1 (en) * 2023-12-06 2025-06-12 Oyster Point Pharma, Inc. Aav vector encoding diamine oxidase and uses thereof
CN117756911B (zh) * 2023-12-26 2024-07-02 无锡佰翱得生物科学股份有限公司 一种溶质载体蛋白urat1及其制备方法和应用
CN117471107B (zh) * 2023-12-27 2024-04-26 湖南家辉生物技术有限公司 检测先天性无毛症的hr突变基因、蛋白、试剂、试剂盒及应用
CN117959323B (zh) * 2024-01-12 2025-01-21 南方医科大学南方医院 环状rna在制备防治放射性肝纤维化的药物中的应用
WO2025155751A1 (en) * 2024-01-17 2025-07-24 Nutcracker Therapeutics, Inc. Improved method for isolating and characterizing proteins
TW202530250A (zh) * 2024-01-25 2025-08-01 大陸商四川至善唯新生物科技有限公司 編碼卵泡抑素的核酸及其用途
KR20250128903A (ko) * 2024-02-20 2025-08-28 가천대학교 산학협력단 통증 치료용 의약 조성물
WO2025212858A1 (en) * 2024-04-03 2025-10-09 Children's Hospital Medical Center Ivt messenger rna and methods of treating or preventing pfic type iv
WO2025233431A1 (en) 2024-05-07 2025-11-13 Immatics Biotechnologies Gmbh Heteromeric proteins comprising three heteromerization improving substitution, production, combinations and applications thereof
CN118406133B (zh) * 2024-05-30 2025-02-28 徐州医科大学 一种多肽5-HT4R-peptide及其应用
WO2025255199A1 (en) 2024-06-05 2025-12-11 Modernatx, Inc. Argininosuccinate synthase 1 and argininosuccinate lyase polypeptides and polynucleotides and uses thereof
CN119345218A (zh) * 2024-10-18 2025-01-24 中南大学湘雅医院 腺苷在治疗蛇毒神经毒性中的应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE202007018832U1 (de) 2006-04-19 2009-09-17 Arcelormittal France Geschweißtes Teil mit sehr hohen mechanischen Eigenschaften aus einem gewalzten und beschichteten Blech
EP2942143A1 (en) 2014-05-09 2015-11-11 Gestamp HardTech AB Methods for joining two blanks and blanks and products obtained
US20170253941A1 (en) 2014-07-30 2017-09-07 Arcelormittal Method for Fabricating Steel Sheet for Press Hardening, and Parts Obtained by this Method
EP3222745A1 (en) 2014-11-19 2017-09-27 Nippon Steel & Sumitomo Metal Corporation Laser welded joint, automotive part, method for producing laser welded joint, and method for manufacturing automotive part

Family Cites Families (1469)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2008526A (en) 1932-11-03 1935-07-16 Wappler Frederick Charles Method and means for treating living tissue
US3467096A (en) 1966-04-12 1969-09-16 Ferrell S Horn Multiple hypodermic syringe arrangement
BE757653A (fr) 1969-10-21 1971-04-16 Ugine Kuhlmann Nouveaux medicaments derives d'acides nucleiques et procedes pour leur preparation
BE786542A (fr) 1971-07-22 1973-01-22 Dow Corning Dispositif d'aspiration permettant d'obtenir des echantillons de cellules
US3906092A (en) 1971-11-26 1975-09-16 Merck & Co Inc Stimulation of antibody response
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US5132418A (en) 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4411657A (en) 1980-05-19 1983-10-25 Anibal Galindo Hypodermic needle
US4973679A (en) 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US4668777A (en) 1981-03-27 1987-05-26 University Patents, Inc. Phosphoramidite nucleoside compounds
US4415732A (en) 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4401796A (en) 1981-04-30 1983-08-30 City Of Hope Research Institute Solid-phase synthesis of polynucleotides
US4373071A (en) 1981-04-30 1983-02-08 City Of Hope Research Institute Solid-phase synthesis of polynucleotides
US4474569A (en) 1982-06-28 1984-10-02 Denver Surgical Developments, Inc. Antenatal shunt
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
US4737462A (en) 1982-10-19 1988-04-12 Cetus Corporation Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β
US4588585A (en) 1982-10-19 1986-05-13 Cetus Corporation Human recombinant cysteine depleted interferon-β muteins
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US4579849A (en) 1984-04-06 1986-04-01 Merck & Co., Inc. N-alkylguanine acyclonucleosides as antiviral agents
US4957735A (en) 1984-06-12 1990-09-18 The University Of Tennessee Research Corporation Target-sensitive immunoliposomes- preparation and characterization
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
US4959314A (en) 1984-11-09 1990-09-25 Cetus Corporation Cysteine-depleted muteins of biologically active proteins
US5036006A (en) 1984-11-13 1991-07-30 Cornell Research Foundation, Inc. Method for transporting substances into living cells and tissues and apparatus therefor
US5116943A (en) 1985-01-18 1992-05-26 Cetus Corporation Oxidation-resistant muteins of Il-2 and other protein
CA1288073C (en) 1985-03-07 1991-08-27 Paul G. Ahlquist Rna transformation vector
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
EP0204401A1 (en) 1985-04-09 1986-12-10 Biogen, Inc. Method of improving the yield of polypeptides produced in a host cell by stabilizing mRNA
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US5017691A (en) 1986-07-03 1991-05-21 Schering Corporation Mammalian interleukin-4
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
US5153319A (en) 1986-03-31 1992-10-06 University Patents, Inc. Process for preparing polynucleotides
US4879111A (en) 1986-04-17 1989-11-07 Cetus Corporation Treatment of infections with lymphokines
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
US6090591A (en) 1987-07-31 2000-07-18 The Board Of Trustees Of The Leland Stanford Junior University Selective amplification of target polynucleotide sequences
FI891436L (fi) 1987-07-31 1989-03-23 Univ Leland Stanford Junior Selektivt flerfaldigande av targetpolynukleotidsekvenser.
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
CA1327358C (en) 1987-11-17 1994-03-01 Morio Fujiu Fluoro cytidine derivatives
JP2846018B2 (ja) 1988-01-21 1999-01-13 ジェネンテク，インコーポレイテッド 核酸配列の増幅および検出
JP2650159B2 (ja) 1988-02-24 1997-09-03 アクゾ・ノベル・エヌ・ベー 核酸増幅方法
CA1340807C (en) 1988-02-24 1999-11-02 Lawrence T. Malek Nucleic acid amplification process
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
DE68923027D1 (de) 1988-03-04 1995-07-20 Cancer Res Campaign Tech Antigene.
FI895955A7 (fi) 1988-04-15 1989-12-13 Protein Design Labs Inc Il-2-reseptorispesifisiä "kimeerisiä" vasta-aineita
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5021335A (en) 1988-06-17 1991-06-04 The Board Of Trustees Of The Leland Stanford Junior University In situ transcription in cells and tissues
US5168038A (en) 1988-06-17 1992-12-01 The Board Of Trustees Of The Leland Stanford Junior University In situ transcription in cells and tissues
US5130238A (en) 1988-06-24 1992-07-14 Cangene Corporation Enhanced nucleic acid amplification process
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
US5759802A (en) 1988-10-26 1998-06-02 Tonen Corporation Production of human serum alubumin A
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5221732A (en) 1988-12-06 1993-06-22 The United States Of America As Represented By The Department Of Health And Human Services Antimicrobial magainin modified peptides
US5262530A (en) 1988-12-21 1993-11-16 Applied Biosystems, Inc. Automated system for polynucleotide synthesis and purification
US5047524A (en) 1988-12-21 1991-09-10 Applied Biosystems, Inc. Automated system for polynucleotide synthesis and purification
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US6673776B1 (en) 1989-03-21 2004-01-06 Vical Incorporated Expression of exogenous polynucleotide sequences in a vertebrate, mammal, fish, bird or human
US5703055A (en) 1989-03-21 1997-12-30 Wisconsin Alumni Research Foundation Generation of antibodies through lipid mediated DNA delivery
DE69034078T2 (de) 1989-03-21 2004-04-01 Vical, Inc., San Diego Expression von exogenen Polynukleotidsequenzen in Wirbeltieren
US6214804B1 (en) 1989-03-21 2001-04-10 Vical Incorporated Induction of a protective immune response in a mammal by injecting a DNA sequence
US5693622A (en) 1989-03-21 1997-12-02 Vical Incorporated Expression of exogenous polynucleotide sequences cardiac muscle of a mammal
US6867195B1 (en) 1989-03-21 2005-03-15 Vical Incorporated Lipid-mediated polynucleotide administration to reduce likelihood of subject's becoming infected
US5012818A (en) 1989-05-04 1991-05-07 Joishy Suresh K Two in one bone marrow surgical needle
IE66597B1 (en) 1989-05-10 1996-01-24 Akzo Nv Method for the synthesis of ribonucleic acid (RNA)
US5332671A (en) 1989-05-12 1994-07-26 Genetech, Inc. Production of vascular endothelial cell growth factor and DNA encoding same
US5240855A (en) 1989-05-12 1993-08-31 Pioneer Hi-Bred International, Inc. Particle gun
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
CA2020958C (en) 1989-07-11 2005-01-11 Daniel L. Kacian Nucleic acid sequence amplification methods
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5545522A (en) 1989-09-22 1996-08-13 Van Gelder; Russell N. Process for amplifying a target polynucleotide sequence using a single primer-promoter complex
AU638762B2 (en) 1989-10-05 1993-07-08 Optein Inc Cell-free synthesis and isolation of novel genes and polypeptides
DE69034150T2 (de) 1989-10-24 2005-08-25 Isis Pharmaceuticals, Inc., Carlsbad 2'-Modifizierte Oligonukleotide
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
US5215899A (en) 1989-11-09 1993-06-01 Miles Inc. Nucleic acid amplification employing ligatable hairpin probe and transcription
NO904633L (no) 1989-11-09 1991-05-10 Molecular Diagnostics Inc Amplifikasjon av nukleinsyrer ved transkriberbar haarnaalsprobe.
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5633076A (en) 1989-12-01 1997-05-27 Pharming Bv Method of producing a transgenic bovine or transgenic bovine embryo
US5697901A (en) 1989-12-14 1997-12-16 Elof Eriksson Gene delivery by microneedle injection
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US6783931B1 (en) 1990-01-11 2004-08-31 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
US7037646B1 (en) 1990-01-11 2006-05-02 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
CA2028849A1 (en) 1990-03-08 1991-09-09 Michinao Mizugaki Monoclonal antibodies, assay method, reagent kit, sarching method and drug missiles using them
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
DK0455905T3 (da) 1990-05-11 1998-12-07 Microprobe Corp Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider
US5194370A (en) 1990-05-16 1993-03-16 Life Technologies, Inc. Promoter ligation activated transcription amplification of nucleic acid sequences
CA2042448A1 (en) 1990-06-05 1991-12-06 Jonathan P. Duvick Antimicrobial peptides and plant disease resistance based thereon
US5637459A (en) 1990-06-11 1997-06-10 Nexstar Pharmaceuticals, Inc. Systematic evolution of ligands by exponential enrichment: chimeric selex
US5447914A (en) 1990-06-21 1995-09-05 Emory University Antimicrobial peptides
AU649066B2 (en) 1990-07-25 1994-05-12 Syngene, Inc. Circular extension for generating multiple nucleic acid complements
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US6140496A (en) 1990-10-09 2000-10-31 Benner; Steven Albert Precursors for deoxyribonucleotides containing non-standard nucleosides
ATE198598T1 (de) 1990-11-08 2001-01-15 Hybridon Inc Verbindung von mehrfachreportergruppen auf synthetischen oligonukleotiden
US5527288A (en) 1990-12-13 1996-06-18 Elan Medical Technologies Limited Intradermal drug delivery device and method for intradermal delivery of drugs
AU648140B2 (en) 1991-02-01 1994-04-14 Virtual Drug Development, Inc. Reverse antimicrobial peptides and antimicrobial compositions
US6100024A (en) 1991-02-08 2000-08-08 Promega Corporation Methods and compositions for nucleic acid detection by target extension and probe amplification
EP1681305A3 (en) 1991-03-18 2008-02-27 New York University Monoclonal and chimeric antibodies specific for human tumor necrosis factor
US5426180A (en) 1991-03-27 1995-06-20 Research Corporation Technologies, Inc. Methods of making single-stranded circular oligonucleotides
TW205553B (enExample) 1991-04-25 1993-05-11 Chugai Pharmaceutical Co Ltd
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5169766A (en) 1991-06-14 1992-12-08 Life Technologies, Inc. Amplification of nucleic acid molecules
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5199441A (en) 1991-08-20 1993-04-06 Hogle Hugh H Fine needle aspiration biopsy apparatus and method
EP0538194B1 (de) 1991-10-17 1997-06-04 Novartis AG Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5298422A (en) 1991-11-06 1994-03-29 Baylor College Of Medicine Myogenic vector systems
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5824307A (en) 1991-12-23 1998-10-20 Medimmune, Inc. Human-murine chimeric antibodies against respiratory syncytial virus
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
EP0625049A4 (en) 1992-01-23 1995-07-12 Vical Inc EX VIVO GENTRANSFER.
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
JP3368603B2 (ja) 1992-02-28 2003-01-20 オリンパス光学工業株式会社 遺伝子治療用処置具
ES2149768T3 (es) 1992-03-25 2000-11-16 Immunogen Inc Conjugados de agentes enlazantes de celulas derivados de cc-1065.
US6174666B1 (en) 1992-03-27 2001-01-16 The United States Of America As Represented By The Department Of Health And Human Services Method of eliminating inhibitory/instability regions from mRNA
US6132419A (en) 1992-05-22 2000-10-17 Genetronics, Inc. Electroporetic gene and drug therapy
US5514545A (en) 1992-06-11 1996-05-07 Trustees Of The University Of Pennsylvania Method for characterizing single cells based on RNA amplification for diagnostics and therapeutics
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US6670178B1 (en) 1992-07-10 2003-12-30 Transkaryotic Therapies, Inc. In Vivo production and delivery of insulinotropin for gene therapy
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
WO1994003637A1 (en) 1992-07-31 1994-02-17 Syntex (Usa) Inc. Method for introducing defined sequences at the 3' end of polynucleotides
US5273525A (en) 1992-08-13 1993-12-28 Btx Inc. Injection and electroporation apparatus for drug and gene delivery
US5240885A (en) 1992-09-21 1993-08-31 Corning Incorporated Rare earth-doped, stabilized cadmium halide glasses
AU5665694A (en) 1992-11-04 1994-05-24 Denver Biomaterials Inc. Apparatus for removal of pleural effusion fluid
DE69303494T2 (de) 1992-11-13 1997-01-16 Idec Pharma Corp Therapeutische verwendung von chimerischen und markierten antikörper gegen menschlichen b lymphozyt beschränkter differenzierung antigen für die behandlung von b-zell-lymphoma
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US5429923A (en) * 1992-12-11 1995-07-04 President And Fellows Of Harvard College Method for detecting hypertrophic cardiomyophathy associated mutations
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
SG44845A1 (en) 1993-01-12 1997-12-19 Biogen Inc Recombitant anti-vla4 antibody molecules
US5607914A (en) 1993-01-13 1997-03-04 Pioneer Hi-Bred International, Inc. Synthetic antimicrobial peptides
US5459235A (en) 1993-03-19 1995-10-17 The Regents Of The University Of California Antimicrobial peptides antibodies and nucleic acid molecules from bovine neutrophils
ES2107205T3 (es) 1993-03-30 1997-11-16 Sanofi Sa Analogos de nucleosidos aciclicos y secuencias oligonucleotidas que los contienen.
FR2703253B1 (fr) 1993-03-30 1995-06-23 Centre Nat Rech Scient Applicateur d'impulsions electriques pour traitement de tissus biologiques.
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
US7135312B2 (en) 1993-04-15 2006-11-14 University Of Rochester Circular DNA vectors for synthesis of RNA and DNA
US5773244A (en) 1993-05-19 1998-06-30 Regents Of The University Of California Methods of making circular RNA
US6541498B2 (en) 1993-05-20 2003-04-01 Texas Biotechnology Benzenesulfonamides and the use thereof to modulate the activity of endothelin
US5851829A (en) 1993-07-16 1998-12-22 Dana-Farber Cancer Institute Method of intracellular binding of target molecules
US6294664B1 (en) 1993-07-29 2001-09-25 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides
US5672491A (en) 1993-09-20 1997-09-30 The Leland Stanford Junior University Recombinant production of novel polyketides
US6432711B1 (en) 1993-11-03 2002-08-13 Diacrin, Inc. Embryonic stem cells capable of differentiating into desired cell lines
US6096503A (en) 1993-11-12 2000-08-01 The Scripps Research Institute Method for simultaneous identification of differentially expresses mRNAs and measurement of relative concentrations
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US7435802B2 (en) 1994-01-25 2008-10-14 Elan Pharaceuticals, Inc. Humanized anti-VLA4 immunoglobulins
US5840299A (en) 1994-01-25 1998-11-24 Athena Neurosciences, Inc. Humanized antibodies against leukocyte adhesion molecule VLA-4
EP0668350B2 (en) 1994-02-16 2008-12-03 The Government of the United States of America, as represented by the Secretary, Department of Health and Human Services Melanoma associated antigenic polypeptide, epitopes thereof and vaccines against melanoma
IL112820A0 (en) 1994-03-07 1995-05-26 Merck & Co Inc Coordinate in vivo gene expression
WO1995025814A1 (en) 1994-03-18 1995-09-28 Lynx Therapeutics, Inc. Oligonucleotide n3'→p5' phosphoramidates: synthesis and compounds; hybridization and nuclease resistance properties
WO1995026204A1 (en) 1994-03-25 1995-10-05 Isis Pharmaceuticals, Inc. Immune stimulation by phosphorothioate oligonucleotide analogs
US5457041A (en) 1994-03-25 1995-10-10 Science Applications International Corporation Needle array and method of introducing biological substances into living cells using the needle array
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US6074642A (en) 1994-05-02 2000-06-13 Alexion Pharmaceuticals, Inc. Use of antibodies specific to human complement component C5 for the treatment of glomerulonephritis
RU2201963C2 (ru) 1994-05-18 2003-04-10 Плант Тек Биотехнологи Гмбх Форшунг Унд Энтвиклунг ПОСЛЕДОВАТЕЛЬНОСТЬ ДНК (ВАРИАНТЫ), РЕКОМБИНАНТНАЯ ДНК, ПРОТЕИН, СПОСОБ ПОЛУЧЕНИЯ ПРОТЕИНА, СПОСОБ ПОЛУЧЕНИЯ МИКРООРГАНИЗМОВ, СПОСОБ ПОЛУЧЕНИЯ КЛЕТОК ГРИБА, СПОСОБ ПОЛУЧЕНИЯ ЛИНЕЙНЫХ α-1,4-ГЛЮКАНОВ И/ИЛИ ФРУКТОЗЫ И СПОСОБ ПОЛУЧЕНИЯ ЛИНЕЙНЫХ α-1,4-ГЛЮКАНОВ И/ИЛИ ФРУКТОЗЫ IN VITRO
US5550109A (en) 1994-05-24 1996-08-27 Magainin Pharmaceuticals Inc. Inducible defensin peptide from mammalian epithelia
EP0802980A1 (en) 1994-06-02 1997-10-29 Chiron Corporation Nucleic acid immunization using a virus-based infection/transfection system
GB9412230D0 (en) 1994-06-17 1994-08-10 Celltech Ltd Interleukin-5 specific recombiant antibodies
US6239116B1 (en) 1994-07-15 2001-05-29 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
WO1996004925A1 (en) 1994-08-12 1996-02-22 Immunomedics, Inc. Immunoconjugates and humanized antibodies specific for b-cell lymphoma and leukemia cells
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5665545A (en) 1994-11-28 1997-09-09 Akzo Nobel N.V. Terminal repeat amplification method
US5641665A (en) 1994-11-28 1997-06-24 Vical Incorporated Plasmids suitable for IL-2 expression
US5588960A (en) 1994-12-01 1996-12-31 Vidamed, Inc. Transurethral needle delivery device with cystoscope and method for treatment of urinary incontinence
US5807718A (en) 1994-12-02 1998-09-15 The Scripps Research Institute Enzymatic DNA molecules
US5585108A (en) 1994-12-30 1996-12-17 Nanosystems L.L.C. Formulations of oral gastrointestinal therapeutic agents in combination with pharmaceutically acceptable clays
JP3840259B2 (ja) 1995-01-06 2006-11-01 プラント リサーチ インターナショナル ベスローテン フェンノートシャップ 炭水化物ポリマー合成酵素をコードするｄｎａ配列及びトランスジェニック植物を製造するための方法
US5795587A (en) 1995-01-23 1998-08-18 University Of Pittsburgh Stable lipid-comprising drug delivery complexes and methods for their production
US5824497A (en) 1995-02-10 1998-10-20 Mcmaster University High efficiency translation of mRNA molecules
EP0727187B1 (en) 1995-02-15 2003-08-06 Joseph Eldor Multiple hole spinal needle
DE69621507T2 (de) 1995-03-28 2003-01-09 Japan Science And Technology Corp., Kawaguchi Verfahren zur molekularen Indexierung von Genen unter Verwendung von Restriktionsenzymen
US5869230A (en) 1995-03-30 1999-02-09 Beth Israel Hospital Association Gene transfer into the kidney
US6020139A (en) * 1995-04-25 2000-02-01 Oridigm Corporation S-adenosyl methionine regulation of metabolic pathways and its use in diagnosis and therapy
US5986054A (en) 1995-04-28 1999-11-16 The Hospital For Sick Children, Hsc Research And Development Limited Partnership Genetic sequences and proteins related to alzheimer's disease
FR2733762B1 (fr) 1995-05-02 1997-08-01 Genset Sa Methode de couplage specifique de la coiffe de l'extremite 5' d'un fragment d'arnm et preparation d'arnm et d'adnc complet
US5700642A (en) 1995-05-22 1997-12-23 Sri International Oligonucleotide sizing using immobilized cleavable primers
US6057291A (en) 1995-06-02 2000-05-02 University Of British Columbia Antimicrobial cationic peptides
US6051429A (en) 1995-06-07 2000-04-18 Life Technologies, Inc. Peptide-enhanced cationic lipid transfections
US6111095A (en) 1995-06-07 2000-08-29 Merck & Co., Inc. Capped synthetic RNA, analogs, and aptamers
US5889136A (en) 1995-06-09 1999-03-30 The Regents Of The University Of Colorado Orthoester protecting groups in RNA synthesis
US5734015A (en) 1995-06-19 1998-03-31 Magainin Pharmaceuticals Inc. Family of linear antimicrobial peptides from hagfish intestine
US5766903A (en) 1995-08-23 1998-06-16 University Technology Corporation Circular RNA and uses thereof
AU6940796A (en) 1995-08-23 1997-03-19 University Of British Columbia, The Antimicrobial cationic peptides and methods of screening for the same
US6265389B1 (en) 1995-08-31 2001-07-24 Alkermes Controlled Therapeutics, Inc. Microencapsulation and sustained release of oligonucleotides
AU7073096A (en) 1995-09-19 1997-04-09 University Of Massachusetts Inhibited biological degradation of oligodeoxynucleotides
US5830879A (en) 1995-10-02 1998-11-03 St. Elizabeth's Medical Center Of Boston, Inc. Treatment of vascular injury using vascular endothelial growth factor
US6265387B1 (en) 1995-10-11 2001-07-24 Mirus, Inc. Process of delivering naked DNA into a hepatocyte via bile duct
US5871697A (en) 1995-10-24 1999-02-16 Curagen Corporation Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing
US6132988A (en) 1995-10-27 2000-10-17 Takeda Chemical Industries, Ltd. DNA encoding a neuronal cell-specific receptor protein
CU22584A1 (es) 1995-11-17 1999-11-03 Centro Inmunologia Molecular Composiciones farmacéuticas que contienen un anticuerpo monoclonal que reconoce el antígeno de diferenciación leucocitario humano cd6 y sus usos para el diagnóstico y tratamiento de la psoriasis
US6090382A (en) 1996-02-09 2000-07-18 Basf Aktiengesellschaft Human antibodies that bind human TNFα
JP2000502254A (ja) 1995-12-13 2000-02-29 ゼネカ・リミテッド 抗真菌タンパク質
US5962271A (en) 1996-01-03 1999-10-05 Cloutech Laboratories, Inc. Methods and compositions for generating full-length cDNA having arbitrary nucleotide sequence at the 3'-end
US5789578A (en) 1996-01-11 1998-08-04 Massey University Methods for the preparation of resins with ligands attached thereto through a linking group comprising sulfide, sulfoxide or sulfone functionality
US7291463B2 (en) 1996-01-23 2007-11-06 Affymetrix, Inc. Nucleic acid labeling compounds
US5714577A (en) 1996-01-26 1998-02-03 University Of Pittsburgh Antimicrobial peptides
US6261584B1 (en) 1996-02-02 2001-07-17 Alza Corporation Sustained delivery of an active agent using an implantable system
US6395292B2 (en) 1996-02-02 2002-05-28 Alza Corporation Sustained delivery of an active agent using an implantable system
AU1874397A (en) 1996-02-16 1997-09-02 Stichting Rega Vzw Hexitol containing oligonucleotides and their use in antisense strategies
US6534312B1 (en) 1996-02-22 2003-03-18 Merck & Co., Inc. Vaccines comprising synthetic genes
US6090391A (en) 1996-02-23 2000-07-18 Aviron Recombinant tryptophan mutants of influenza
US5994308A (en) 1996-02-28 1999-11-30 Board Of Trustees Of Southern Illinois University Broad spectrum antimicrobial peptides containing a tryptophan triplet and methods of use
US6300487B1 (en) 1996-03-19 2001-10-09 Cell Therapuetics, Inc. Mammalian lysophosphatidic acid acyltransferase
SE9601245D0 (sv) 1996-03-29 1996-03-29 Pharmacia Ab Chimeric superantigens and their use
US5773696A (en) 1996-03-29 1998-06-30 Monsanto Company Antifungal polypeptide and methods for controlling plant pathogenic fungi
TW517061B (en) 1996-03-29 2003-01-11 Pharmacia & Amp Upjohn Ab Modified/chimeric superantigens and their use
JPH09278726A (ja) * 1996-04-11 1997-10-28 Takeshi Imanishi 新規リポソーム
US5712127A (en) 1996-04-29 1998-01-27 Genescape Inc. Subtractive amplification
US5853719A (en) 1996-04-30 1998-12-29 Duke University Methods for treating cancers and pathogen infections using antigen-presenting cells loaded with RNA
US7329741B2 (en) 1996-06-05 2008-02-12 Chiron Corporation Polynucleotides that hybridize to DP-75 and their use
US6300484B1 (en) 1996-06-05 2001-10-09 Chiron Corporation DNA encoding DP. 75 and a process for its use
WO1997048370A2 (en) 1996-06-21 1997-12-24 Merck & Co., Inc. Vaccines comprising synthetic genes
JP2002515786A (ja) 1996-06-28 2002-05-28 ソントラ メディカル，エル．ピー． 経皮輸送の超音波増強
US5677124A (en) 1996-07-03 1997-10-14 Ambion, Inc. Ribonuclease resistant viral RNA standards
US5939262A (en) 1996-07-03 1999-08-17 Ambion, Inc. Ribonuclease resistant RNA preparation and utilization
US5856127A (en) 1996-07-26 1999-01-05 The Research Foundation Of State University Of New York Antimicrobial peptides
US7288266B2 (en) 1996-08-19 2007-10-30 United States Of America As Represented By The Secretary, Department Of Health And Human Services Liposome complexes for increased systemic delivery
EP0960191A4 (en) 1996-08-22 2003-07-23 Univ Pennsylvania COMPOSITIONS AND METHOD FOR USE OF DEFENSIN
US5849546A (en) 1996-09-13 1998-12-15 Epicentre Technologies Corporation Methods for using mutant RNA polymerases with reduced discrimination between non-canonical and canonical nucleoside triphosphates
US6114148C1 (en) 1996-09-20 2012-05-01 Gen Hospital Corp High level expression of proteins
ES2263181T5 (es) 1996-09-24 2011-04-07 Genentech, Inc. Una familia de genes que codifican péptidos relacionados con la apoptosis, péptidos codificados por ellos y los métodos de uso de los mismos.
US6214966B1 (en) 1996-09-26 2001-04-10 Shearwater Corporation Soluble, degradable poly(ethylene glycol) derivatives for controllable release of bound molecules into solution
US6610661B1 (en) 1996-10-11 2003-08-26 The Regents Of The University Of California Immunostimulatory polynucleotide/immunomodulatory molecule conjugates
EP0839912A1 (en) 1996-10-30 1998-05-06 Instituut Voor Dierhouderij En Diergezondheid (Id-Dlo) Infectious clones of RNA viruses and vaccines and diagnostic assays derived thereof
GB9623051D0 (en) 1996-11-06 1997-01-08 Schacht Etienne H Delivery of DNA to target cells in biological systems
US5980887A (en) 1996-11-08 1999-11-09 St. Elizabeth's Medical Center Of Boston Methods for enhancing angiogenesis with endothelial progenitor cells
US6121436A (en) 1996-12-13 2000-09-19 Monsanto Company Antifungal polypeptide and methods for controlling plant pathogenic fungi
US5759179A (en) 1996-12-31 1998-06-02 Johnson & Johnson Medical, Inc. Needle and valve assembly for use with a catheter
KR100566859B1 (ko) 1997-01-21 2006-04-03 제너럴 하스피톨 코포레이션 Ｒｎａ-단백질 융합물을 이용한 단백질의 선별
EP0855184A1 (en) 1997-01-23 1998-07-29 Grayson B. Dr. Lipford Pharmaceutical composition comprising a polynucleotide and an antigen especially for vaccination
IL131131A0 (en) 1997-02-07 2001-01-28 Merck & Co Inc Synthetic hiv gag genes
US6228640B1 (en) 1997-02-07 2001-05-08 Cem Cezayirli Programmable antigen presenting cell of CD34 lineage
US6251665B1 (en) 1997-02-07 2001-06-26 Cem Cezayirli Directed maturation of stem cells and production of programmable antigen presenting dentritic cells therefrom
US6696291B2 (en) 1997-02-07 2004-02-24 Merck & Co., Inc. Synthetic HIV gag genes
US6576752B1 (en) 1997-02-14 2003-06-10 Isis Pharmaceuticals, Inc. Aminooxy functionalized oligomers
US5998374A (en) 1997-02-28 1999-12-07 The Regents Of University Of California Clavaspirins
US5837860A (en) 1997-03-05 1998-11-17 Molecular Tool, Inc. Covalent attachment of nucleic acid molecules onto solid-phases via disulfide bonds
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US6406705B1 (en) 1997-03-10 2002-06-18 University Of Iowa Research Foundation Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant
US6306393B1 (en) 1997-03-24 2001-10-23 Immunomedics, Inc. Immunotherapy of B-cell malignancies using anti-CD22 antibodies
US6261281B1 (en) 1997-04-03 2001-07-17 Electrofect As Method for genetic immunization and introduction of molecules into skeletal muscle and immune cells
US5914269A (en) 1997-04-04 1999-06-22 Isis Pharmaceuticals, Inc. Oligonucleotide inhibition of epidermal growth factor receptor expression
GB2324370B (en) 1997-04-14 1999-03-03 Stuart Harbron Detection of hybrid double-stranded DNA with antibody after enzyme degradation of excess single-standed DNA
WO1998047913A2 (en) 1997-04-18 1998-10-29 The University Of Medicine And Dentistry Of New Jersey Inhibition of hiv-1 replication by a tat rna-binding domain peptide analog
US5958688A (en) 1997-04-28 1999-09-28 The Trustees Of The University Of Pennsylvania Characterization of mRNA patterns in neurites and single cells for medical diagnosis and therapeutics
US6235883B1 (en) 1997-05-05 2001-05-22 Abgenix, Inc. Human monoclonal antibodies to epidermal growth factor receptor
US5989911A (en) 1997-05-09 1999-11-23 University Of Massachusetts Site-specific synthesis of pseudouridine in RNA
EP2113247A3 (en) * 1997-05-14 2010-05-05 The University Of British Columbia High efficiency encapsulation of nucleic acids in lipid vesicles
AU7600098A (en) * 1997-05-27 1998-12-30 Icos Corporation Novel lysophosphatidic acid acyltransferase
NL1006164C2 (nl) 1997-05-29 1998-12-01 Univ Leiden Antimicrobiële peptiden.
US6124091A (en) 1997-05-30 2000-09-26 Research Corporation Technologies, Inc. Cell growth-controlling oligonucleotides
US6589940B1 (en) 1997-06-06 2003-07-08 Dynavax Technologies Corporation Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof
ATE432348T1 (de) 1997-06-06 2009-06-15 Univ California Inhibitoren von immunstimulatorischen dna sequenz aktivität
DE19726167B4 (de) * 1997-06-20 2008-01-24 Sanofi-Aventis Deutschland Gmbh Insulin, Verfahren zu seiner Herstellung und es enthaltende pharmazeutische Zubereitung
JP2002510319A (ja) 1997-07-01 2002-04-02 アイシス・ファーマシューティカルス・インコーポレーテッド オリゴヌクレオチドの消化管を介したデリバリーのための組成物及び方法
US5994511A (en) 1997-07-02 1999-11-30 Genentech, Inc. Anti-IgE antibodies and methods of improving polypeptides
FR2766191B1 (fr) 1997-07-21 2000-11-10 Ifremer Peptides anti-microbiens de crustaces
ES2284209T3 (es) 1997-07-21 2007-11-01 Active Biotech Ab Citolisis de celulas diana por conjugados de superantigenos que inducen la activacion de celulas t.
US20030073640A1 (en) 1997-07-23 2003-04-17 Ribozyme Pharmaceuticals, Inc. Novel compositions for the delivery of negatively charged molecules
JP2001512140A (ja) 1997-07-31 2001-08-21 アカデミック・ジーケヌース・ビーアイジェイ・デ・ユニバーシティト・ヴァン・アムステルダム 敗血症治療のための抗菌性及びエンドトキシン不活性化能を有する新規な合成ペプチド
WO1999006073A1 (en) 1997-07-31 1999-02-11 St. Elizabeth's Medical Center Of Boston, Inc. Method for the treatment of grafts
GB9718908D0 (en) * 1997-09-05 1997-11-12 Rowett Research Services Limit Proteins
US6576755B1 (en) 1997-09-10 2003-06-10 Zymogenetics, Inc. Beta-defensins
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
AU752725B2 (en) 1997-09-18 2002-09-26 Trustees Of The University Of Pennsylvania, The Attenuated vif DNA immunization cassettes for genetic vaccines
JP2002508299A (ja) * 1997-09-19 2002-03-19 セクイター， インク． センスｍＲＮＡ治療
JP2001517422A (ja) 1997-09-25 2001-10-09 アカデミス・ジーケンハイス・ベイ・デ・ウニフェルジテイト・ファン・アムステルダム 単離したおよび組換えによる抗菌ペプチドトロンボシジン−１（ｔｃ−１）およびトロンボシジン−２（ｔｃ−２）またはその変異体
US6004573A (en) 1997-10-03 1999-12-21 Macromed, Inc. Biodegradable low molecular weight triblock poly(lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties
WO1999018221A1 (en) 1997-10-07 1999-04-15 University Of Maryland Biotechnology Institute Method for introducing and expressing rna in animal cells
JP2001520041A (ja) 1997-10-20 2001-10-30 ジェンザイム トランスジェニックス コーポレイション 新規な改変核酸配列並びに細胞システムにおいてｍＲＮＡレベル及び蛋白質発現を増大させる方法
US6019747A (en) 1997-10-21 2000-02-01 I-Flow Corporation Spring-actuated infusion syringe
JP2001520889A (ja) 1997-10-24 2001-11-06 バレンティス，インコーポレイティド ポリヌクレオチドトランスフェクション複合体を調製する方法
WO1999024596A1 (en) 1997-11-12 1999-05-20 Valentis, Inc. Expression plasmids for multiepitope nucleic acid-based vaccines
US6548633B1 (en) 1998-12-22 2003-04-15 Genset, S.A. Complementary DNA's encoding proteins with signal peptides
JP2001523480A (ja) 1997-11-20 2001-11-27 バイカル インコーポレイテッド サイトカイン発現ポリヌクレオチドおよびそれらの組成物を用いた癌の処置
US7655777B2 (en) 1997-11-24 2010-02-02 Monsanto Technology Llc Nucleic acid molecules associated with the tocopherol pathway
US6267987B1 (en) 1997-12-12 2001-07-31 Samyang Corporation Positively charged poly[alpha-(omega-aminoalkyl) glycolic acid] for the delivery of a bioactive agent via tissue and cellular uptake
US6517869B1 (en) 1997-12-12 2003-02-11 Expression Genetics, Inc. Positively charged poly(alpha-(omega-aminoalkyl)lycolic acid) for the delivery of a bioactive agent via tissue and cellular uptake
WO1999033982A2 (en) 1997-12-23 1999-07-08 Chiron Corporation Human genes and gene expression products i
US6320017B1 (en) 1997-12-23 2001-11-20 Inex Pharmaceuticals Corp. Polyamide oligomers
US6383811B2 (en) 1997-12-30 2002-05-07 Mirus Corporation Polyampholytes for delivering polyions to a cell
EP1044021B1 (en) 1998-01-05 2009-09-23 The University of Washington Enhanced transport using membrane disruptive agents
WO1999034857A1 (en) 1998-01-08 1999-07-15 Sontra Medical, Inc. Sonophoretic enhanced transdermal transport
US8287483B2 (en) 1998-01-08 2012-10-16 Echo Therapeutics, Inc. Method and apparatus for enhancement of transdermal transport
NL1008139C2 (nl) 1998-01-27 1999-07-28 Stichting Tech Wetenschapp Antimicrobiële peptiden.
JP2002503701A (ja) 1998-02-18 2002-02-05 ハーバー−ユーシーエルエイ リサーチ アンド エデュケーション インスティテュート 抗菌性ペプチドおよび誘導したメタペプチド
US6365346B1 (en) 1998-02-18 2002-04-02 Dade Behring Inc. Quantitative determination of nucleic acid amplification products
US5888793A (en) * 1998-02-25 1999-03-30 Incyte Pharmaceuticals, Inc. Human lysophosphatidic acid acyltransferase
US5955310A (en) 1998-02-26 1999-09-21 Novo Nordisk Biotech, Inc. Methods for producing a polypeptide in a bacillus cell
AU3549799A (en) * 1998-04-06 1999-10-25 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The Mammalian selenoprotein differentially expressed in tumor cells
US6849417B1 (en) * 1998-04-06 2005-02-01 The United States Of America As Represented By The Department Of Health And Human Services Mammalian selenoprotein differentially expressed in tumor cells
US6432925B1 (en) 1998-04-16 2002-08-13 John Wayne Cancer Institute RNA cancer vaccine and methods for its use
US6429301B1 (en) 1998-04-17 2002-08-06 Whitehead Institute For Biomedical Research Use of a ribozyme to join nucleic acids and peptides
GB9808327D0 (en) 1998-04-20 1998-06-17 Chiron Spa Antidiotypic compounds
CN1637146A (zh) 1998-04-23 2005-07-13 宝生物工程株式会社 Dna的合成方法
US6395253B2 (en) 1998-04-23 2002-05-28 The Regents Of The University Of Michigan Microspheres containing condensed polyanionic bioactive agents and methods for their production
US20020064517A1 (en) 1998-04-30 2002-05-30 Stewart A. Cederholm-Williams Fibrin sealant as a transfection/transformation vehicle for gene therapy
US20090208418A1 (en) 2005-04-29 2009-08-20 Innexus Biotechnology Internaltional Ltd. Superantibody synthesis and use in detection, prevention and treatment of disease
KR20010071279A (ko) 1998-05-20 2001-07-28 추후제출 간세포를 표적으로하는 폴리에틸렌 글리콜-접합된폴리-ｌ-리신 고분자로된 유전자 운반체
US6503231B1 (en) 1998-06-10 2003-01-07 Georgia Tech Research Corporation Microneedle device for transport of molecules across tissue
US7091192B1 (en) 1998-07-01 2006-08-15 California Institute Of Technology Linear cyclodextrin copolymers
EP1117720A4 (en) 1998-07-13 2001-11-14 Expression Genetics Inc POLYESTER POLY-L-LYSINE ANALOG USED AS A BIODEGRADABLE SOLUBLE GENE CONVEYOR
US6222030B1 (en) 1998-08-03 2001-04-24 Agilent Technologies, Inc. Solid phase synthesis of oligonucleotides using carbonate protecting groups and alpha-effect nucleophile deprotection
KR101063278B1 (ko) 1998-08-11 2011-09-07 바이오겐 아이덱 인크. Ｂ-세포 림프종을 치료하기 위한 항-ｃｄ２０ 항체를 포함하는 약제
US6476189B1 (en) 1998-08-12 2002-11-05 National Institute Of Agrobiological Sciences Antibacterial peptides and antibacterial agents containing such peptides as an effective ingredient
GB9817662D0 (en) 1998-08-13 1998-10-07 Crocker Peter J Substance delivery
US6288212B1 (en) 1998-08-28 2001-09-11 The University Of British Columbia Anti-endotoxic, antimicrobial cationic peptides and methods of use therefor
US20020065236A1 (en) * 1998-09-09 2002-05-30 Yew Nelson S. CpG reduced plasmids and viral vectors
US20090017533A1 (en) 1998-09-29 2009-01-15 Shire Human Genetic Therapies, Inc., A Delaware Corporation Optimized messenger rna
US6924365B1 (en) 1998-09-29 2005-08-02 Transkaryotic Therapies, Inc. Optimized messenger RNA
EP1133513A4 (en) 1998-11-03 2002-07-03 Univ Yale MULTI-DOMAIN POLYNUCLEOTIDE MOLECULAR DETECTORS
EP1131093A4 (en) 1998-11-09 2002-05-02 Idec Pharma Corp TREATMENT OF HEMATOLOGICAL VILTIES ASSOCIATED WITH CIRCULATING TUMOR CELLS USING CHIMERIC ANTI-CD20 ANTIBODIES
AU761516B2 (en) 1998-11-09 2003-06-05 Biogen Inc. Chimeric anti-CD20 antibody treatment of patients receiving BMT or PBSC transplants
WO2000027340A2 (en) 1998-11-12 2000-05-18 The Children's Medical Center Corporation USE OF t-RNA AND FRAGMENTS FOR INHIBITING ANGIOGENESIS AND COMPOSITIONS THEREOF
JP3141107B2 (ja) 1998-11-16 2001-03-05 工業技術院長 ヒト由来ブラディオン蛋白質、それをコードするｄｎａ及びそれらの使用
US6248268B1 (en) 1998-11-16 2001-06-19 Xc Corporation Process of making microparticles of a thermally-gelled polysaccharide
US6210931B1 (en) 1998-11-30 2001-04-03 The United States Of America As Represented By The Secretary Of Agriculture Ribozyme-mediated synthesis of circular RNA
JP2000175684A (ja) * 1998-12-14 2000-06-27 Eiken Chem Co Ltd 新規アシルトランスフェラーゼをコードする遺伝子
US20040171980A1 (en) 1998-12-18 2004-09-02 Sontra Medical, Inc. Method and apparatus for enhancement of transdermal transport
EP1141376A4 (en) 1998-12-23 2002-03-13 Human Genome Sciences PEPTIDOGLYCANE RECOGNITION PROTEINS
EP2314700A1 (en) 1999-01-28 2011-04-27 Medical College of Georgia Research Institute, Inc Composition and method for in vivo and in vitro attenuation of gene expression using double stranded RNA
GB9902000D0 (en) * 1999-01-30 1999-03-17 Delta Biotechnology Ltd Process
WO2000050586A2 (en) 1999-02-22 2000-08-31 European Molecular Biology Laboratory In vitro translation system
US6255476B1 (en) 1999-02-22 2001-07-03 Pe Corporation (Ny) Methods and compositions for synthesis of labelled oligonucleotides and analogs on solid-supports
US7629311B2 (en) 1999-02-24 2009-12-08 Edward Lewis Tobinick Methods to facilitate transmission of large molecules across the blood-brain, blood-eye, and blood-nerve barriers
EP1574210B1 (en) 1999-02-26 2016-04-06 Novartis Vaccines and Diagnostics, Inc. Microemulsions with adsorbed macromolecules
US6107460A (en) 1999-03-01 2000-08-22 The Board Of Regents Of The University Of Oklahoma Antimicrobial peptides and methods of use thereof
US8410248B2 (en) 1999-03-12 2013-04-02 Human Genome Sciences Inc. HWBAO62 polypeptides
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
US7244710B2 (en) 2002-05-21 2007-07-17 Zengen, Inc. Treatment of ophthalmic infections using antimicrobial peptides
AU778809B2 (en) 1999-03-29 2004-12-23 Statens Serum Institut Method for producing a nucleotide sequence construct with optimised codons for an HIV genetic vaccine based on primary, early HIV isolate and synthetic envelope BX08 constructs
EP1177231B1 (en) 1999-04-09 2009-08-19 Invitrogen Dynal AS Process for the preparation of monodisperse polymer particles
AU776362B2 (en) 1999-05-04 2004-09-09 Roche Innovation Center Copenhagen A/S L-ribo-LNA analogues
KR20020027311A (ko) 1999-05-07 2002-04-13 제넨테크, 인크. Ｂ 세포 표면 마커에 결합하는 길항물질을 이용한자가면역 질환의 치료
KR20020011985A (ko) 1999-05-07 2002-02-09 파르마솔 게엠베하 액상 및 고체상 지질 혼합물에 기초한 지질입자들 및 그의제조방법
US7582301B1 (en) 1999-05-17 2009-09-01 Conjuchem Biotechnologies, Inc. Long-lasting antiviral fusion inhibitor peptide conjugates comprising albumin and human immunodeficiency virus (HIV) peptides
US6346382B1 (en) 1999-06-01 2002-02-12 Vanderbilt University Human carbamyl phosphate synthetase I polymorphism and diagnostic methods related thereto
US6611707B1 (en) 1999-06-04 2003-08-26 Georgia Tech Research Corporation Microneedle drug delivery device
US6743211B1 (en) 1999-11-23 2004-06-01 Georgia Tech Research Corporation Devices and methods for enhanced microneedle penetration of biological barriers
WO2000075356A1 (en) 1999-06-04 2000-12-14 Lin Shi Lung Rna polymerase chain reaction
US6303573B1 (en) 1999-06-07 2001-10-16 The Burnham Institute Heart homing peptides and methods of using same
AU776268B2 (en) 1999-06-08 2004-09-02 Aventis Pasteur Immunostimulant oligonucleotide
EP1194167B1 (en) 1999-06-09 2009-08-19 Immunomedics, Inc. Immunotherapy of autoimmune disorders using antibodies which target b-cells
US6949245B1 (en) 1999-06-25 2005-09-27 Genentech, Inc. Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies
US20030153050A1 (en) 1999-06-28 2003-08-14 Conklin Darrell C. Helical polypeptide zalpha29
NZ516236A (en) 1999-06-30 2004-12-24 Advanced Cell Tech Inc Altering life span of a recipient cell by transferring cell cytoplasm from a donor cell for use in gene therapy and cloning
US6514948B1 (en) 1999-07-02 2003-02-04 The Regents Of The University Of California Method for enhancing an immune response
FR2796072B1 (fr) 1999-07-08 2003-09-19 Centre Nat Rech Scient Peptides anti-microbiens de mollusques
BR0012325A (pt) 1999-07-09 2002-05-21 American Home Prod Métodos e composições para prevenção da formação de rna anormal durante a transcrição de uma sequência de plasmìdeo
CA2311201A1 (en) 1999-08-05 2001-02-05 Genset S.A. Ests and encoded human proteins
US8557244B1 (en) 1999-08-11 2013-10-15 Biogen Idec Inc. Treatment of aggressive non-Hodgkins lymphoma with anti-CD20 antibody
US7071293B1 (en) 1999-08-18 2006-07-04 The University Of Iowa Research Foundation Alpha helical peptides with broad spectrum antimicrobial activity that are insensitive to salt
JP2002300878A (ja) 1999-08-19 2002-10-15 Chugai Pharmaceut Co Ltd 新規ｂＨＬＨ型転写因子遺伝子、ＤＥＣ２
CN1371416B (zh) 1999-08-24 2012-10-10 梅达里克斯公司 人ctla-4抗体及其应用
US20050112141A1 (en) 2000-08-30 2005-05-26 Terman David S. Compositions and methods for treatment of neoplastic disease
US20040106567A1 (en) 1999-09-07 2004-06-03 Hagstrom James E. Intravascular delivery of non-viral nucleic acid
ATE289630T1 (de) 1999-09-09 2005-03-15 Curevac Gmbh Transfer von mrnas unter verwendung von polykationischen verbindungen
WO2001021810A1 (en) 1999-09-17 2001-03-29 Aventis Pasteur Limited Chlamydia antigens and corresponding dna fragments and uses thereof
US6623457B1 (en) 1999-09-22 2003-09-23 Becton, Dickinson And Company Method and apparatus for the transdermal administration of a substance
WO2002064799A2 (en) 1999-09-28 2002-08-22 Transkaryotic Therapies, Inc. Optimized messenger rna
US6511832B1 (en) 1999-10-06 2003-01-28 Texas A&M University System In vitro synthesis of capped and polyadenylated mRNAs using baculovirus RNA polymerase
IL148922A0 (en) 1999-10-06 2002-09-12 Quark Biotech Inc Method for enrichment of natural antisense messenger rna
EP1101771A1 (en) 1999-11-15 2001-05-23 Korea Kumho Petrochemical Co. Ltd. Pathogen-induced genes from Capsicum annuum
US7060291B1 (en) 1999-11-24 2006-06-13 Transave, Inc. Modular targeted liposomal delivery system
US6573361B1 (en) 1999-12-06 2003-06-03 Monsanto Technology Llc Antifungal proteins and methods for their use
US6613026B1 (en) 1999-12-08 2003-09-02 Scimed Life Systems, Inc. Lateral needle-less injection apparatus and method
US6277974B1 (en) 1999-12-14 2001-08-21 Cogent Neuroscience, Inc. Compositions and methods for diagnosing and treating conditions, disorders, or diseases involving cell death
EP1240182A2 (en) 1999-12-15 2002-09-18 Cubist Pharmaceuticals, Inc. Daptomycin analogs and their use as antibacterial agents
US6245929B1 (en) 1999-12-20 2001-06-12 General Electric Company Catalyst composition and method for producing diaryl carbonates, using bisphosphines
DE60015090T2 (de) 1999-12-22 2006-03-02 Basell Poliolefine Italia S.P.A. Alpha-olefin enthaltendes polymerisationskatalysatorsystem, das ein aromatisches silan enthält
WO2001051092A2 (en) 2000-01-07 2001-07-19 University Of Washington Enhanced transport of agents using membrane disruptive agents
AU2001232485A1 (en) 2000-01-13 2001-07-24 Amsterdam Support Diagnostics B.V. A universal nucleic acid amplification system for nucleic acids in a sample
DE10001377A1 (de) * 2000-01-14 2001-08-02 Univ Mainz Johannes Gutenberg bHLH-Transkriptionsfaktor ASCL3 und diesen enthaltendes Arzneimittel
CA2395811A1 (en) 2000-01-31 2001-08-02 Human Genome Sciences, Inc. Nucleic acids, proteins, and antibodies
EP1253947A4 (en) 2000-01-31 2005-01-05 Univ California IMMUNOMODULATORY POLYNUCLEOTIDES FOR THE TREATMENT OF INFECTION BY AN INTRACELLULAR PATHOGEN
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
AU2001238595A1 (en) 2000-02-22 2001-09-03 Shearwater Corporation N-maleimidyl polymer derivatives
DE1257584T1 (de) 2000-02-24 2003-05-28 Lilly Co Eli Humanisierte antikörper, die amyloid beta peptid demarkieren
EP1130091A3 (en) 2000-03-01 2001-11-14 Message Pharmaceuticals, Inc. Bacterial RNaseP Proteins and their use in identifying antibacterial compounds
AU2001245427A1 (en) 2000-03-03 2001-09-17 Valentis, Inc. Nucleic acid formulations for gene delivery and methods of use
GB0006572D0 (en) 2000-03-17 2000-05-10 Isis Innovation Novel transcription transactivator protein
JP2003529774A (ja) * 2000-03-31 2003-10-07 ジェネンテック・インコーポレーテッド 遺伝子発現を検出し定量するための構成物及び方法
KR20020091170A (ko) 2000-03-31 2002-12-05 아이덱 파마슈티칼즈 코포레이션 Ｂ 세포 림프종의 치료를 위한 항-사이토카인 항체 또는길항제 및 항-ｃｄ２０의 조합된 사용
US6565572B2 (en) 2000-04-10 2003-05-20 Sdgi Holdings, Inc. Fenestrated surgical screw and method
US6368801B1 (en) 2000-04-12 2002-04-09 Molecular Staging, Inc. Detection and amplification of RNA using target-mediated ligation of DNA by RNA ligase
EP2275557A1 (en) 2000-04-12 2011-01-19 Human Genome Sciences, Inc. Albumin fusion proteins
US20010046496A1 (en) 2000-04-14 2001-11-29 Brettman Lee R. Method of administering an antibody
US6375972B1 (en) 2000-04-26 2002-04-23 Control Delivery Systems, Inc. Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof
US7871598B1 (en) 2000-05-10 2011-01-18 Novartis Ag Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use
US20040229271A1 (en) 2000-05-19 2004-11-18 Williams Richard B. Compositions and methods for the identification and selection of nucleic acids and polypeptides
WO2001092523A2 (en) 2000-05-30 2001-12-06 Curagen Corporation Human polynucleotides and polypeptides encoded thereby
WO2001093902A2 (en) 2000-06-07 2001-12-13 Biosynexus Incorporated Immunostimulatory rna/dna hybrid molecules
ATE343589T1 (de) 2000-06-23 2006-11-15 Wyeth Corp Modofiziertes morbillivirus v proteine
US6337317B1 (en) 2000-06-27 2002-01-08 The University Of British Columbia Antimicrobial peptides and methods of use thereof
US6492328B2 (en) 2000-06-28 2002-12-10 The University Of Iowa Research Foundation Novispirins: antimicrobial peptides
WO2002002606A2 (en) 2000-07-03 2002-01-10 Chiron S.P.A. Immunisation against chlamydia pneumoniae
US6440096B1 (en) 2000-07-14 2002-08-27 Becton, Dickinson And Co. Microdevice and method of manufacturing a microdevice
AU7569501A (en) 2000-07-21 2002-02-05 Glaxo Group Ltd Codon-optimized papilloma virus sequences
US6696238B2 (en) 2000-07-28 2004-02-24 Christopher J. Murphy Transplant media
US6727066B2 (en) 2000-07-28 2004-04-27 Incyte Corporation Genes expressed in treated human C3A liver cell cultures
US6902734B2 (en) 2000-08-07 2005-06-07 Centocor, Inc. Anti-IL-12 antibodies and compositions thereof
US7052888B2 (en) * 2000-08-21 2006-05-30 Millennium Pharmaceuticals, Inc. ACTR-1 a novel human acyltransferase and uses thereof
US6875907B2 (en) 2000-09-13 2005-04-05 Pioneer Hi-Bred International, Inc. Antimicrobial peptides and methods of use
US6696038B1 (en) 2000-09-14 2004-02-24 Expression Genetics, Inc. Cationic lipopolymer as biocompatible gene delivery agent
US20040142474A1 (en) 2000-09-14 2004-07-22 Expression Genetics, Inc. Novel cationic lipopolymer as a biocompatible gene delivery agent
AU2001290078A1 (en) 2000-09-20 2002-04-02 Ruggero Della Bitta Stem cell therapy
JP4413493B2 (ja) 2000-10-04 2010-02-10 サンタリス ファーマ アー／エス プリンｌｎａ類似体の改善された合成方法
WO2002028165A2 (en) 2000-10-04 2002-04-11 The Trustees Of The University Of Pennsylvania Compositions and methods of using capsid protein from flaviviruses and pestiviruses
DE10050274A1 (de) * 2000-10-09 2002-04-18 Henkel Kgaa Verfahren zur in vitro Bestimmung der Hautalterung
US6998115B2 (en) 2000-10-10 2006-02-14 Massachusetts Institute Of Technology Biodegradable poly(β-amino esters) and uses thereof
US6649138B2 (en) 2000-10-13 2003-11-18 Quantum Dot Corporation Surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media
US7202226B2 (en) 2000-10-23 2007-04-10 Detroit R & D Augmentation of wound healing by elF-4E mRNA and EGF mRNA
US20030077604A1 (en) 2000-10-27 2003-04-24 Yongming Sun Compositions and methods relating to breast specific genes and proteins
GB0026924D0 (en) 2000-11-03 2000-12-20 Univ Cambridge Tech Antibacterial agents
US20020132788A1 (en) 2000-11-06 2002-09-19 David Lewis Inhibition of gene expression by delivery of small interfering RNA to post-embryonic animal cells in vivo
WO2002040545A2 (en) 2000-11-17 2002-05-23 The Government Of The United States, As Represented By The Secretary Of The Department Of Health And Human Services Reduction of the nonspecific animal toxicity of immunotoxins by mutating the framework regions of the fv to lower the isoelectric point
WO2002044399A2 (en) 2000-11-28 2002-06-06 Rosetta Inpharmatics, Inc. In vitro transcription method for rna amplification
JP2004535765A (ja) 2000-12-07 2004-12-02 カイロン コーポレイション 前立腺癌においてアップレギュレートされた内因性レトロウイルス
US20020130430A1 (en) 2000-12-29 2002-09-19 Castor Trevor Percival Methods for making polymer microspheres/nanospheres and encapsulating therapeutic proteins and other products
US7708915B2 (en) 2004-05-06 2010-05-04 Castor Trevor P Polymer microspheres/nanospheres and encapsulating therapeutic proteins therein
DK1351981T3 (da) 2001-01-19 2012-11-26 Vironovative Bv Et virus, der forårsager luftvejssygdom hos modtagelige pattedyr
EP1224943A1 (en) 2001-01-19 2002-07-24 Crucell Holland B.V. Fibronectin as a tumor marker detected by phage antibodies
US20040110191A1 (en) 2001-01-31 2004-06-10 Winkler Matthew M. Comparative analysis of nucleic acids using population tagging
US20040142433A1 (en) 2001-02-02 2004-07-22 Padgett Hal S. Polynucleotide sequence variants
JP2004527236A (ja) 2001-02-14 2004-09-09 ベイラー　カレッジ　オブ　メディスン Ｒｎａ増幅の方法及び組成物
US6652886B2 (en) 2001-02-16 2003-11-25 Expression Genetics Biodegradable cationic copolymers of poly (alkylenimine) and poly (ethylene glycol) for the delivery of bioactive agents
US6887847B2 (en) 2001-02-16 2005-05-03 University Of Pittsburgh Virus derived antimicrobial peptides
US6835713B2 (en) 2001-02-16 2004-12-28 University Of Pittsburgh Virus derived antimicrobial peptides
DE10109897A1 (de) 2001-02-21 2002-11-07 Novosom Ag Fakultativ kationische Liposomen und Verwendung dieser
US7232425B2 (en) 2001-03-02 2007-06-19 Sorenson Development, Inc. Apparatus and method for specific interstitial or subcutaneous diffusion and dispersion of medication
AU2002242474B2 (en) 2001-03-09 2004-05-20 Gene Stream Pty Ltd Novel expression vectors
JP2002262882A (ja) 2001-03-12 2002-09-17 Nisshinbo Ind Inc Ｒｎａの増幅法
FR2822164B1 (fr) 2001-03-19 2004-06-18 Centre Nat Rech Scient Polypeptides derives des arn polymerases, et leurs utilisations
US6520949B2 (en) 2001-04-02 2003-02-18 Martin St. Germain Method and apparatus for administering fluid to animals subcutaneously
WO2003008537A2 (en) * 2001-04-06 2003-01-30 Mannkind Corporation Epitope sequences
DE10119005A1 (de) 2001-04-18 2002-10-24 Roche Diagnostics Gmbh Verfahren zur Proteinexpression ausgehend von stabilisierter linearer kurzer DNA in zellfreien in vitro-Transkription/Translations-Systemen mit Exonuklease-haltigen Lysaten oder in einem zellulären System enthaltend Exonukleasen
US7314858B2 (en) 2001-04-18 2008-01-01 The Regents Of The University Of California Retrocyclins: antiviral and antimicrobial peptides
US20030171253A1 (en) 2001-04-19 2003-09-11 Averil Ma Methods and compositions relating to modulation of A20
ES2295351T3 (es) 2001-04-21 2008-04-16 Curevac Gmbh Dispositivo para la inyeccion de rnam.
CA2445260C (en) 2001-04-23 2011-02-01 Amaxa Gmbh Buffer solution for electroporation and a method comprising the use of the same
US7560424B2 (en) 2001-04-30 2009-07-14 Zystor Therapeutics, Inc. Targeted therapeutic proteins
US6777187B2 (en) 2001-05-02 2004-08-17 Rubicon Genomics, Inc. Genome walking by selective amplification of nick-translate DNA library and amplification from complex mixtures of templates
GB0111015D0 (en) * 2001-05-04 2001-06-27 Norsk Hydro As Genetic material
AU2002308623A1 (en) 2001-05-08 2002-11-18 Magnatech International, L.P. Electronic length control wire pay-off system and method
US20050137155A1 (en) 2001-05-18 2005-06-23 Sirna Therapeutics, Inc. RNA interference mediated treatment of Parkinson disease using short interfering nucleic acid (siNA)
US8137911B2 (en) 2001-05-22 2012-03-20 Cellscript, Inc. Preparation and use of single-stranded transcription substrates for synthesis of transcription products corresponding to target sequences
US7514098B2 (en) 2001-05-30 2009-04-07 The Board Of Trustees Of The Leland Stanford Junior University Use of targeted cross-linked nanoparticles for in vivo gene delivery
PT1857122E (pt) 2001-06-05 2011-03-07 Curevac Gmbh Arnm estabilizado com teor de g/c aumentado, codificando para um antigénio viral
US7235358B2 (en) 2001-06-08 2007-06-26 Expression Diagnostics, Inc. Methods and compositions for diagnosing and monitoring transplant rejection
WO2002102839A2 (en) 2001-06-18 2002-12-27 Novartis Ag Novel g-protein coupled receptors and dna sequences thereof
US7785610B2 (en) 2001-06-21 2010-08-31 Dynavax Technologies Corporation Chimeric immunomodulatory compounds and methods of using the same—III
US7547551B2 (en) 2001-06-21 2009-06-16 University Of Antwerp. Transfection of eukaryontic cells with linear polynucleotides by electroporation
EP1270732A1 (en) 2001-06-21 2003-01-02 Schuler, Gerold Improved transfection of eukaryontic cells with linear polynucleotides by electroporation
WO2003002604A2 (en) 2001-06-26 2003-01-09 Novartis Ag G protein coupled receptors and dna sequences thereof
SE0102327D0 (sv) 2001-06-28 2001-06-28 Active Biotech Ab A novel engineered superantigen for human therapy
US6872705B2 (en) 2001-07-13 2005-03-29 Allergan, Inc. Use of antimicrobial peptides as preservatives in ophthalmic preparations, including solutions, emulsions, and suspensions
US20040236092A1 (en) 2001-07-13 2004-11-25 Roman Dziarski Peptidologlycan recognition protein encoding nucleic acids and methods of use thereof
US6586524B2 (en) 2001-07-19 2003-07-01 Expression Genetics, Inc. Cellular targeting poly(ethylene glycol)-grafted polymeric gene carrier
AU2002354893A1 (en) * 2001-07-20 2003-03-03 Technion Research And Development Foundation Ltd. Methods of generating human cardiac cells and tissues and uses thereof
ATE502119T1 (de) * 2001-07-25 2011-04-15 Oncomedx Inc Verfahren zur bewertung pathologischer krankheitszustände unter verwendung extrazellulärer rna
US7169750B2 (en) 2001-07-31 2007-01-30 Anormed, Inc. Methods to mobilize progenitor/stem cells
ATE481497T1 (de) 2001-08-01 2010-10-15 Univ Utah Am n-terminus trunkierte isoformen von zyklischen phosphodiesterasen pde3a
AU2002335668A1 (en) 2001-08-08 2003-02-24 The Research Foundation Of The State University Of New York Muc7d1 peptides as antifungal and antibacterial agents
US6743598B2 (en) 2001-08-10 2004-06-01 Mycologics, Inc. Methods for the identification of fungal glucose utilization inhibitors and antifungal agents
US6835536B2 (en) 2001-08-21 2004-12-28 Micrologix Biotech Inc. Antimicrobial cationic peptides and formulations thereof
WO2003018798A2 (en) 2001-08-27 2003-03-06 Novartis Ag G-protein coupled receptor and dna sequences thereof
US7456335B2 (en) * 2001-09-03 2008-11-25 Basf Plant Science Gmbh Nucleic acid sequences and their use in methods for achieving pathogen resistance in plants
US20040142325A1 (en) 2001-09-14 2004-07-22 Liat Mintz Methods and systems for annotating biomolecular sequences
AU2002336746A1 (en) 2001-09-21 2003-04-01 Message Pharmaceuticals, Inc. Inhibitors of rnase p proteins as antibacterial compounds
IL161100A0 (en) 2001-09-28 2004-08-31 Max Planck Gesellschaft Identification of novel genes coding for small temporal rnas
WO2003028657A2 (en) 2001-10-03 2003-04-10 The Johns Hopkins University Compositions for oral gene therapy and methods of using same
AR045702A1 (es) 2001-10-03 2005-11-09 Chiron Corp Composiciones de adyuvantes.
DE10148886A1 (de) 2001-10-04 2003-04-30 Avontec Gmbh Inhibition von STAT-1
US7276489B2 (en) 2002-10-24 2007-10-02 Idera Pharmaceuticals, Inc. Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5′ ends
CN1318586C (zh) 2001-11-05 2007-05-30 詹森药业有限公司 短的双链RNAs的体外合成方法
WO2003042383A1 (en) 2001-11-14 2003-05-22 Toyo Boseki Kabushiki Kaisha Dna synthesis promoters, dna polymerase-associated factors and utilization thereof
US20040076978A1 (en) 2001-11-14 2004-04-22 Catherine Verfaillie Method to identify genes associated with chronic myelogenous leukemia
WO2003044482A2 (en) 2001-11-16 2003-05-30 The University Of Tennessee Research Corporation Recombinant antibody fusion proteins and methods for detection of apoptotic cells
US6478825B1 (en) 2001-11-28 2002-11-12 Osteotech, Inc. Implant, method of making same and use of the implant for the treatment of bone defects
US20050032062A1 (en) 2001-11-29 2005-02-10 Salah-Dine Chibout Methods for the assessment and prognosis of sarcoidosis
CA2409775C (en) 2001-12-03 2010-07-13 F. Hoffmann-La Roche Ag Reversibly modified thermostable enzymes for dna synthesis and amplification in vitro
DE60235413D1 (de) 2001-12-07 2010-04-01 Novartis Vaccines & Diagnostic Bei prostatakrebs hochreguliertes endogenes retrovirus
US20060275747A1 (en) 2001-12-07 2006-12-07 Hardy Stephen F Endogenous retrovirus up-regulated in prostate cancer
JP4822490B2 (ja) 2001-12-07 2011-11-24 ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド 腫瘍形成形質転換に関連する内因性レトロウイルスポリペプチド
WO2003051923A2 (en) 2001-12-17 2003-06-26 Novartis Ag Novel g-protein coupled receptors and dna sequences thereof
DE10162480A1 (de) 2001-12-19 2003-08-07 Ingmar Hoerr Die Applikation von mRNA für den Einsatz als Therapeutikum gegen Tumorerkrankungen
JP2005514429A (ja) 2001-12-21 2005-05-19 アルコン、インコーポレイテッド 眼／耳用薬物のキャリヤーとしての合成無機質ナノ粒子の使用
AU2003235707A1 (en) 2002-01-18 2003-07-30 Curevac Gmbh Immunogenic preparations and vaccines on the basis of mrna
AU2003303082B2 (en) 2002-01-30 2009-07-02 Dana-Farber Cancer Institute, Inc. Compositions and methods related to TIM-3, a Th1-specific cell surface molecule
EP1474432A1 (en) 2002-02-04 2004-11-10 Biomira Inc. Immunostimulatory, covalently lipidated oligonucleotides
CA2473144C (en) 2002-02-05 2013-05-28 Genentech, Inc. Protein purification
FR2835749B1 (fr) 2002-02-08 2006-04-14 Inst Nat Sante Rech Med Composition pharmaceutique ameliorant le transfert de gene in vivo
DE10207178A1 (de) 2002-02-19 2003-09-04 Novosom Ag Komponenten für die Herstellung amphoterer Liposomen
AR038568A1 (es) 2002-02-20 2005-01-19 Hoffmann La Roche Anticuerpos anti-a beta y su uso
US20050222064A1 (en) 2002-02-20 2005-10-06 Sirna Therapeutics, Inc. Polycationic compositions for cellular delivery of polynucleotides
US7354742B2 (en) 2002-02-22 2008-04-08 Ortho-Mcneil Pharmaceutical, Inc. Method for generating amplified RNA
NZ535690A (en) 2002-02-26 2009-04-30 Maxygen Inc Novel flavivirus antigens
ATE475431T1 (de) 2002-03-04 2010-08-15 Imclone Llc Kdr-spezifische humane antikörper und deren anwendung
US20060088532A1 (en) * 2002-03-07 2006-04-27 Kari Alitalo Lymphatic and blood endothelial cell genes
JP4679822B2 (ja) 2002-03-13 2011-05-11 ノバルティス アーゲー 医薬微粒子
WO2003078593A2 (en) 2002-03-15 2003-09-25 Epigenomics Ag Discovery and diagnostic methods using 5-methylcytosine dna glycosylase
US7074596B2 (en) 2002-03-25 2006-07-11 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Synthesis and use of anti-reverse mRNA cap analogues
IL164376A0 (en) * 2002-04-03 2005-12-18 Applied Research Systems Ox4or binding agents, their preparation and pharmaceutical compositions containing them
ES2543710T3 (es) 2002-04-04 2015-08-21 Zoetis Belgium S.A. Oligorribonucleótidos inmunoestimulantes que contienen G y U
JP4761710B2 (ja) * 2002-04-05 2011-08-31 アムジェン インコーポレイテッド 選択的ｏｐｇｌ経路インヒビターとしてのヒト抗ｏｐｇｌ中和抗体
EP1497327A2 (en) 2002-04-17 2005-01-19 Novartis AG Method for the identification of inhibitors of the binding of are-containing mrna and an hur protein
GB0209539D0 (en) 2002-04-26 2002-06-05 Avecia Ltd Monomer Polymer and process
EP1361277A1 (en) 2002-04-30 2003-11-12 Centre National De La Recherche Scientifique (Cnrs) Optimization of transgene expression in mammalian cells
AU2003217531A1 (en) 2002-05-02 2003-11-17 Massachusetts Eye And Ear Infirmary Ocular drug delivery systems and use thereof
PT2371392E (pt) 2002-05-02 2015-10-07 Wyeth Holdings Llc Conjugados de derivado da caliqueamicina - transportador
US20040018525A1 (en) 2002-05-21 2004-01-29 Bayer Aktiengesellschaft Methods and compositions for the prediction, diagnosis, prognosis, prevention and treatment of malignant neoplasma
US7374930B2 (en) 2002-05-21 2008-05-20 Expression Genetics, Inc. GLP-1 gene delivery for the treatment of type 2 diabetes
DE10224200C1 (de) 2002-05-31 2003-08-21 Artus Ges Fuer Molekularbiolog Vermehrung von Ribonukleinsäuren
AU2003237367A1 (en) 2002-06-03 2003-12-19 Chiron Corporation Use of nrg4, or inhibitors thereof, in the treatment of colon and pancreatic cancer
SE0201907D0 (sv) 2002-06-19 2002-06-19 Atos Medical Ab Plaster for tracheostoma valves
EP1527175B1 (en) 2002-06-24 2009-05-27 Exiqon A/S Methods and systems for detection and isolation of a nucleotide sequence
DK1519714T3 (da) 2002-06-28 2011-01-31 Protiva Biotherapeutics Inc Fremgangsmåde og apparat til fremstilling af liposomer
EP1552298A4 (en) 2002-07-01 2006-11-08 Kenneth S Warren Inst Inc RECOMBINANT TISSUE-PROOFING CYTOKINS AND NUCLEIC ACIDS COORDINATING THEREOF FOR THE PROTECTION, RECOVERY AND IMPROVEMENT OF CELLS, TISSUE AND ORGANS THEREOF
DE10229872A1 (de) 2002-07-03 2004-01-29 Curevac Gmbh Immunstimulation durch chemisch modifizierte RNA
GB0215509D0 (en) 2002-07-04 2002-08-14 Novartis Ag Marker genes
DE60336736D1 (de) 2002-07-16 2011-05-26 VGX Pharmaceuticals LLC Codon-optimierte synthetische plasmide
EP1543157A4 (en) 2002-07-24 2006-11-15 Ptc Therapeutics Inc METHODS FOR IDENTIFYING SMALL MOLECULES MODULATING PREMATURE TRANSLATION TERMINATION AND DEGRADATION OF INDUCED MRNA BY NON-SENSE MUTATION
EP1393745A1 (en) 2002-07-29 2004-03-03 Hybridon, Inc. Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5'ends
EP1386925A1 (en) 2002-07-31 2004-02-04 Girindus AG Method for preparing oligonucleotides
US6653468B1 (en) 2002-07-31 2003-11-25 Isis Pharmaceuticals, Inc. Universal support media for synthesis of oligomeric compounds
US20040220127A1 (en) 2002-08-09 2004-11-04 Paul Sternberg Methods and compositions relating to 5'-chimeric ribonucleic acids
EP1873180B1 (en) 2002-08-14 2014-05-07 Novartis AG Ophthalmic device made from a radiation-curable prepolymer
BR122012021252B8 (pt) 2002-09-06 2021-05-25 Cerulean Pharma Inc polímeros à base de ciclodextrina para o fornecimento de agentes terapêuticos ligados a eles por covalência
MXPA05002632A (es) 2002-09-09 2005-09-20 Nektar Therapeutics Al Corp Metodo para preparar derivados de polimeros solubles en agua que portan un acido carboxilico terminal.
US7534872B2 (en) 2002-09-27 2009-05-19 Syngen, Inc. Compositions and methods for the use of FMOC derivatives in DNA/RNA synthesis
KR100932340B1 (ko) 2002-10-17 2009-12-16 젠맵 에이/에스 Ｃｄ20에 대한 인간 모노클로날 항체
ATE492636T1 (de) 2002-10-22 2011-01-15 Eisai R&D Man Co Ltd Spezifisch in postmitotischen dopamin- produzierenden neuronalen vorläuferzellen exprimiertes gen
US7892793B2 (en) * 2002-11-04 2011-02-22 University Of Massachusetts Allele-specific RNA interference
AU2003291726A1 (en) 2002-11-04 2004-06-07 Xenoport, Inc. Gemcitabine prodrugs, pharmaceutical compositions and uses thereof
AU2003297557B2 (en) 2002-11-21 2009-02-26 Cellscript, Inc. Methods for using primers that encode one strand of a double-stranded promoter
US7491234B2 (en) 2002-12-03 2009-02-17 Boston Scientific Scimed, Inc. Medical devices for delivery of therapeutic agents
CN103833854B (zh) 2002-12-16 2017-12-12 健泰科生物技术公司 免疫球蛋白变体及其用途
AU2003302743B2 (en) 2002-12-23 2008-09-04 Dynavax Technologies Corporation Branched immunomodulatory compounds and methods of using the same
US7169892B2 (en) 2003-01-10 2007-01-30 Astellas Pharma Inc. Lipid-peptide-polymer conjugates for long blood circulation and tumor specific drug delivery systems
US7851453B2 (en) 2003-01-16 2010-12-14 Idera Pharmaceuticals, Inc. Modulation of immunostimulatory properties of oligonucleotide-based compounds by utilizing modified immunostimulatory dinucleotides
US20080227085A1 (en) 2003-01-17 2008-09-18 Pellegrini Matthew C Methods and Systems for the Identification of Rna Regulatory Sequences and Compounds that Modulate their Function
US9068234B2 (en) 2003-01-21 2015-06-30 Ptc Therapeutics, Inc. Methods and agents for screening for compounds capable of modulating gene expression
US8426194B2 (en) 2003-01-21 2013-04-23 Ptc Therapeutics, Inc. Methods and agents for screening for compounds capable of modulating VEGF expression
US8460864B2 (en) 2003-01-21 2013-06-11 Ptc Therapeutics, Inc. Methods for identifying compounds that modulate untranslated region-dependent gene expression and methods of using same
US20040147027A1 (en) 2003-01-28 2004-07-29 Troy Carol M. Complex for facilitating delivery of dsRNA into a cell and uses thereof
RU2358763C2 (ru) 2003-02-10 2009-06-20 Элан Фармасьютикалз, Инк. Композиции иммуноглобулина и способ их получения
US20040167090A1 (en) 2003-02-21 2004-08-26 Monahan Sean D. Covalent modification of RNA for in vitro and in vivo delivery
US7091185B2 (en) 2003-02-24 2006-08-15 Dow Global Technologies Inc. Periodic antimicrobial peptides
WO2004076655A1 (en) * 2003-02-27 2004-09-10 Basf Aktiengesellschaft Modified nitrilases and their use in methods for the production of carboxylic acids
CA2450289A1 (en) 2003-03-20 2005-05-19 Imclone Systems Incorporated Method of producing an antibody to epidermal growth factor receptor
US7320961B2 (en) 2003-03-24 2008-01-22 Abbott Laboratories Method for treating a disease, disorder or adverse effect caused by an elevated serum concentration of an UGT1A1 substrate
US7704712B2 (en) 2003-03-25 2010-04-27 Stratagene California DNA polymerase fusions and uses thereof
US20040242502A1 (en) 2003-04-08 2004-12-02 Galenica Pharmaceuticals, Inc. Semi-synthetic saponin analogs with carrier and immune stimulatory activities for DNA and RNA vaccines
EP1613350B1 (en) 2003-04-09 2009-03-18 Genentech, Inc. Therapy of autoimmune disease in a patient with an inadequate response to a tnf-alpha inhibitor
CA2522349A1 (en) 2003-04-17 2004-11-04 Alnylam Pharmaceuticals, Inc. Protected monomers
JP2006525405A (ja) 2003-05-05 2006-11-09 ベン‐グリオン ユニバーシティ オブ ザ ネゲヴ リサーチ アンド デベロップメント オーソリティ 注入可能な架橋されたポリマー調製物およびその使用
PT1624891E (pt) 2003-05-06 2010-01-05 Syntonix Pharmaceuticals Inc Proteínas quiméricas de factor de coagulação-fc destinadas ao tratamento da hemofilia
TWI353991B (en) 2003-05-06 2011-12-11 Syntonix Pharmaceuticals Inc Immunoglobulin chimeric monomer-dimer hybrids
US7348004B2 (en) 2003-05-06 2008-03-25 Syntonix Pharmaceuticals, Inc. Immunoglobulin chimeric monomer-dimer hybrids
US9567591B2 (en) 2003-05-15 2017-02-14 Mello Biotechnology, Inc. Generation of human embryonic stem-like cells using intronic RNA
GB0313132D0 (en) 2003-06-06 2003-07-09 Ich Productions Ltd Peptide ligands
WO2004108883A2 (en) * 2003-06-10 2004-12-16 Toolgen, Inc. Transducible dna-binding proteins
EP1636385A4 (en) 2003-06-24 2010-06-02 Mirus Bio Corp INHIBITION OF GENE FUNCTION BY IN VIVO DISTRIBUTION OF GENE EXPRESSION INHIBITORS BASED ON POLYNUCLEOTIDES IN MAMMALIAN CELLS
GB0316089D0 (en) 2003-07-09 2003-08-13 Xo Bioscience Ltd Differentiation method
KR100992646B1 (ko) 2003-07-09 2010-11-05 제이에스알 가부시끼가이샤 파장판
US8592197B2 (en) 2003-07-11 2013-11-26 Novavax, Inc. Functional influenza virus-like particles (VLPs)
US7575572B2 (en) 2003-07-15 2009-08-18 Spinal Generations, Llc Method and device for delivering medicine to bone
US20050013870A1 (en) 2003-07-17 2005-01-20 Toby Freyman Decellularized extracellular matrix of conditioned body tissues and uses thereof
TW201319088A (zh) 2003-07-18 2013-05-16 Amgen Inc 對肝細胞生長因子具專一性之結合劑
DE10334371A1 (de) 2003-07-25 2005-02-17 Bavarian Nordic A/S Reaktorboden eines Reaktors
EP1648914A4 (en) 2003-07-31 2009-12-16 Regulus Therapeutics Inc OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA
DE10335833A1 (de) 2003-08-05 2005-03-03 Curevac Gmbh Transfektion von Blutzellen mit mRNA zur Immunstimulation und Gentherapie
CL2004001996A1 (es) 2003-08-08 2005-05-06 Eyetech Pharmaceuticals Inc Aptameros anti-vegf (factor de crecimiento endotelial vascular) con bloqueo nucleotidico 5'-5' o 3'-3' invertido, composicion que lo contiene, util para trastornos de neovascularizacion.
US8668926B1 (en) 2003-09-15 2014-03-11 Shaker A. Mousa Nanoparticle and polymer formulations for thyroid hormone analogs, antagonists, and formulations thereof
US7135010B2 (en) 2003-09-30 2006-11-14 Damage Control Surgical Technologies, Inc. Method and apparatus for rapid deployment chest drainage
CA2541138A1 (en) 2003-10-06 2005-05-06 Novartis Ag Use of genetic polymorphisms that associate with efficacy of treatment of inflammatory disease
US20050130201A1 (en) 2003-10-14 2005-06-16 Dharmacon, Inc. Splint-assisted enzymatic synthesis of polyribounucleotides
DE10347710B4 (de) 2003-10-14 2006-03-30 Johannes-Gutenberg-Universität Mainz Rekombinante Impfstoffe und deren Verwendung
BRPI0416262B1 (pt) 2003-11-05 2022-04-12 Roche Glycart Ag Anticorpo anti-cd20 humano tipo ii humanizado, seu método de produção, seus usos, bem como polinucleotídeo isolado, vetor de expressão e composição farmacêutica
WO2005047536A2 (en) 2003-11-13 2005-05-26 Novartis Ag Detection of genomic amplification and deletion in cancer
US20070054278A1 (en) 2003-11-18 2007-03-08 Applera Corporation Polymorphisms in nucleic acid molecules encoding human enzyme proteins, methods of detection and uses thereof
US7699852B2 (en) 2003-11-19 2010-04-20 Zimmer Spine, Inc. Fenestrated bone tap and method
US20050153333A1 (en) 2003-12-02 2005-07-14 Sooknanan Roy R. Selective terminal tagging of nucleic acids
WO2005055945A2 (en) 2003-12-08 2005-06-23 Gel-Del Technologies, Inc. Mucoadhesive drug delivery devices and methods of making and using thereof
US7674884B2 (en) 2003-12-10 2010-03-09 Novimmune S.A. Neutralizing antibodies and methods of use thereof
WO2005084180A2 (en) 2003-12-19 2005-09-15 University Of Cincinnati Polyamides and polyamide complexes for delivery of oligonucleotide decoys
JP2005179268A (ja) 2003-12-19 2005-07-07 Gc Corp 口腔用組成物
ES2775204T3 (es) 2003-12-23 2020-07-24 Genentech Inc Nuevos anticuerpos anti IL13 y usos de los mismos
US20050143336A1 (en) * 2003-12-30 2005-06-30 Board Of Regents, The University Of Texas System Methods and compositions for improved non-viral gene therapy
WO2005072710A2 (en) 2004-01-28 2005-08-11 Johns Hopkins University Drugs and gene carrier particles that rapidly move through mucous barriers
DK1716233T3 (da) * 2004-01-30 2009-10-26 Maxygen Holdings Ltd Reguleret stopkodongennemlæsning
US7309487B2 (en) * 2004-02-09 2007-12-18 George Inana Methods and compositions for detecting and treating retinal diseases
AU2005214331B2 (en) 2004-02-12 2011-09-15 Eisai, Inc. Monoclonal antibodies that specifically bind to folate receptor alpha
US20070265220A1 (en) 2004-03-15 2007-11-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
EP1728801A4 (en) 2004-03-24 2009-10-21 Chugai Pharmaceutical Co Ltd SUBTYP OF A HUMANIZED ANTIBODY AGAINST THE INTERLEUKIN-6 RECEPTOR
WO2005098433A2 (en) 2004-04-01 2005-10-20 Novartis Ag Diagnostic assays for alzheimer’s disease
KR20070044805A (ko) 2004-04-15 2007-04-30 키아스마, 인코포레이티드 생물학적 장벽 투과를 촉진시킬 수 있는 조성물
EP1740946B1 (en) 2004-04-20 2013-11-06 Genmab A/S Human monoclonal antibodies against cd20
ES2246694B1 (es) 2004-04-29 2007-05-01 Instituto Cientifico Y Tecnologico De Navarra, S.A. Nanoparticulas pegiladas.
WO2005108411A2 (en) 2004-05-05 2005-11-17 Isis Pharmaceuticals, Inc. Substituted pixyl protecting groups for oligonucleotide synthesis
EP1765294B1 (en) 2004-05-12 2008-09-24 Baxter International Inc. Nucleic acid microspheres, production and delivery thereof
US20080103053A1 (en) 2005-11-22 2008-05-01 Helicos Biosciences Corporation Methods and compositions for sequencing a nucleic acid
CA2568772A1 (en) 2004-06-01 2005-12-15 San Diego State University Foundation Expression system based on recombinant vesicular stomatitis virus synthesizing t7 rna polymerase
EP2527447A1 (en) * 2004-06-03 2012-11-28 Athlomics Pty Ltd Agents and methods for diagnosing stress
CA2569645C (en) 2004-06-07 2014-10-28 Protiva Biotherapeutics, Inc. Cationic lipids and methods of use
JP4796062B2 (ja) * 2004-06-07 2011-10-19 プロチバ バイオセラピューティクス インコーポレイティッド 脂質封入干渉ｒｎａ
EP1773240B1 (en) 2004-06-11 2019-11-20 Trustees of the Tufts College Silk-based drug delivery system
US7527947B2 (en) 2004-06-14 2009-05-05 Novozymes A/S Signal peptide for producing a polypeptide
WO2006046978A2 (en) 2004-06-28 2006-05-04 Argos Therapeutics, Inc. Cationic peptide-mediated transformation
KR101100059B1 (ko) 2004-06-30 2011-12-29 넥타르 테라퓨틱스 중합체­인자 ｉｘ 부분의 접합체
US7700555B2 (en) 2004-07-15 2010-04-20 Joslin Diabetes Center, Inc. Methods of treating diabetes
DE102004035227A1 (de) 2004-07-21 2006-02-16 Curevac Gmbh mRNA-Gemisch zur Vakzinierung gegen Tumorerkrankungen
WO2006093526A2 (en) 2004-07-21 2006-09-08 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a modified or non-natural nucleobase
US7603349B1 (en) 2004-07-29 2009-10-13 Yahoo! Inc. User interfaces for search systems using in-line contextual queries
GB0417487D0 (en) 2004-08-05 2004-09-08 Novartis Ag Organic compound
US7968324B2 (en) 2004-08-13 2011-06-28 Barry J Marshall Helicobacter system and uses thereof
US7291208B2 (en) 2004-08-13 2007-11-06 Gore Enterprise Holdings, Inc. Grooved active and passive adsorbent filters
SE0402025D0 (sv) 2004-08-13 2004-08-13 Active Biotech Ab Treatment of hyperproliferative disease with superantigens in combination with another anticancer agent
CA2478458A1 (en) 2004-08-20 2006-02-20 Michael Panzara Treatment of pediatric multiple sclerosis
PL2386640T3 (pl) 2004-08-26 2015-08-31 Engeneic Molecular Delivery Pty Ltd Dostarczanie funkcjonalnych kwasów nukleinowych do komórek ssaczych za pośrednictwem nienaruszonych minikomórek pochodzenia bakteryjnego
DE102004042546A1 (de) 2004-09-02 2006-03-09 Curevac Gmbh Kombinationstherapie zur Immunstimulation
JP4890457B2 (ja) * 2004-09-02 2012-03-07 アイシス ファーマシューティカルズ， インコーポレーテッド オリゴマー合成のための高分子ビーズ
US7501486B2 (en) 2004-09-07 2009-03-10 Burnham Institute For Medical Research Peptides that selectively home to heart vasculature and related conjugates and methods
CN101060864A (zh) * 2004-09-21 2007-10-24 阿尼西瓦股份有限公司 多核苷酸的递送
EP1799271A4 (en) 2004-09-21 2010-05-05 Anesiva Inc DISPOSAL OF POLYNUCLEOTIDES
GB0421639D0 (en) * 2004-09-29 2004-10-27 Proteome Sciences Plc Methods and compositions relating to alzheimer's disease
US8663599B1 (en) 2004-10-05 2014-03-04 Gp Medical, Inc. Pharmaceutical composition of nanoparticles
EP1811018A4 (en) 2004-10-12 2007-11-28 Tissue Targeting Japan Inc PROGENITOR FOR BRAIN DISPOSAL FROM BONE MARROW
WO2006044456A1 (en) 2004-10-13 2006-04-27 Ptc Therapeutics, Inc. Compounds for nonsense suppression, and methods for their use
US8057821B2 (en) 2004-11-03 2011-11-15 Egen, Inc. Biodegradable cross-linked cationic multi-block copolymers for gene delivery and methods of making thereof
WO2006047842A2 (en) 2004-11-08 2006-05-11 K.U. Leuven Research And Development Modified nucleosides for rna interference
JP2008520742A (ja) 2004-11-23 2008-06-19 ピーティーシー セラピューティクス， インコーポレイテッド Ｖｅｇｆ産生の阻害に有用なカルバゾール誘導体、カルボリン誘導体およびインドール誘導体
US7964571B2 (en) 2004-12-09 2011-06-21 Egen, Inc. Combination of immuno gene therapy and chemotherapy for treatment of cancer and hyperproliferative diseases
EP1856179B1 (en) 2004-12-10 2013-05-15 Kala Pharmaceuticals, Inc. Functionalized poly (ether-anhydride) block copolymers
WO2006071903A2 (en) 2004-12-28 2006-07-06 Ptc Therapeutics, Inc. Cell based methods and systems for the identification of rna regulatory sequences and compounds that modulate their functions
US8187570B1 (en) 2005-01-04 2012-05-29 Gp Medical, Inc. Nanoparticles for protein drug delivery
US8192718B1 (en) 2005-01-04 2012-06-05 Gp Medical, Inc. Pharmaceutical composition of nanoparticles
CA2594233C (en) * 2005-01-07 2015-02-24 Lexicon Pharmaceuticals, Inc. Monoclonal antibodies against angiopoietin-like protein 4 (angptl4 )
US8535702B2 (en) 2005-02-01 2013-09-17 Boston Scientific Scimed, Inc. Medical devices having porous polymeric regions for controlled drug delivery and regulated biocompatibility
US7404969B2 (en) 2005-02-14 2008-07-29 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules
CA2597724A1 (en) 2005-02-14 2007-08-02 Sirna Therapeutics, Inc. Cationic lipids and formulated molecular compositions containing them
EP2287608B1 (en) 2005-03-11 2014-01-08 Firalis SAS Biomarkers for cardiovascular side-effects induced by cox-2 inhibitory compounds
US20060257902A1 (en) * 2005-03-25 2006-11-16 Ambion, Inc. Methods and compositions for depleting abundant RNA transcripts
US8415325B2 (en) 2005-03-31 2013-04-09 University Of Delaware Cell-mediated delivery and targeted erosion of noncovalently crosslinked hydrogels
KR101288729B1 (ko) 2005-04-01 2013-07-23 인터자인 테크놀로지스, 인코포레이티드 약물 전달용 중합체성 마이셀
CA2604844A1 (en) 2005-04-07 2006-10-19 Novartis Vaccines And Diagnostics, Inc. Cancer-related genes
AU2006235276A1 (en) 2005-04-07 2006-10-19 Novartis Vaccines And Diagnostics Inc. CACNA1E in cancer diagnosis, detection and treatment
US8273339B2 (en) 2005-04-12 2012-09-25 Nektar Therapeutics Polymer-based compositions and conjugates of antimicrobial agents
CA2609788A1 (en) 2005-04-26 2006-11-02 Coley Pharmaceutical Gmbh Modified oligoribonucleotide analogs with enhanced immunostimulatory activity
EP2418278A3 (en) 2005-05-09 2012-07-04 Ono Pharmaceutical Co., Ltd. Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics
US8246995B2 (en) 2005-05-10 2012-08-21 The Board Of Trustees Of The Leland Stanford Junior University Hydrophobic nanotubes and nanoparticles as transporters for the delivery of drugs into cells
US20070072175A1 (en) 2005-05-13 2007-03-29 Biogen Idec Ma Inc. Nucleotide array containing polynucleotide probes complementary to, or fragments of, cynomolgus monkey genes and the use thereof
US20060265771A1 (en) 2005-05-17 2006-11-23 Lewis David L Monitoring microrna expression and function
DE102005023170A1 (de) 2005-05-19 2006-11-23 Curevac Gmbh Optimierte Formulierung für mRNA
SI2002003T1 (sl) 2005-05-27 2016-05-31 Ospedale San Raffaele S.R.L. Genski vektor, ki vsebuje mi-RNA
EP1888638A2 (en) 2005-06-03 2008-02-20 Genentech, Inc. Method of producing antibodies with modified fucosylation level
US7550264B2 (en) 2005-06-10 2009-06-23 Datascope Investment Corporation Methods and kits for sense RNA synthesis
EP2279758B1 (en) 2005-06-16 2015-02-25 Nektar Therapeutics Conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates
JP5570721B2 (ja) 2005-06-17 2014-08-13 ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル ナノ粒子の製造方法、システム、及び材料
US8202835B2 (en) 2005-06-17 2012-06-19 Yitzchak Hillman Disease treatment via antimicrobial peptides or their inhibitors
US8101385B2 (en) 2005-06-30 2012-01-24 Archemix Corp. Materials and methods for the generation of transcripts comprising modified nucleotides
US8105813B2 (en) 2005-06-30 2012-01-31 Archemix Corp. Materials and methods for the generation of fully 2′-modified nucleic acid transcripts
US20080220471A1 (en) 2005-07-27 2008-09-11 Genentech, Inc. Vectors and Methods Using Same
PT1919503E (pt) 2005-08-10 2015-01-05 Macrogenics Inc Identificação e manipulação de anticorpos com a regiões de fc variantes e métodos de utilização dos mesmos
ES2937245T3 (es) 2005-08-23 2023-03-27 Univ Pennsylvania ARN que contiene nucleósidos modificados y métodos de uso del mismo
US9012219B2 (en) 2005-08-23 2015-04-21 The Trustees Of The University Of Pennsylvania RNA preparations comprising purified modified RNA for reprogramming cells
US20070048741A1 (en) 2005-08-24 2007-03-01 Getts Robert C Methods and kits for sense RNA synthesis
US8715677B2 (en) 2005-09-01 2014-05-06 Celgene Corporation Immunological uses of immunomodulatory compounds for vaccine and anti-infectious disease therapy
WO2007026249A2 (en) 2005-09-01 2007-03-08 Novartis Vaccines And Diagnostics Gmbh & Co Kg Multiple vaccination including serogroup c meningococcus
US8420605B2 (en) 2005-09-07 2013-04-16 The University Of Strathclyde Hydrogel compositions
US20120021042A1 (en) 2005-09-15 2012-01-26 Steffen Panzner Efficient Method For Loading Amphoteric Liposomes With Nucleic Acid Active Substances
DE102005046490A1 (de) 2005-09-28 2007-03-29 Johannes-Gutenberg-Universität Mainz Modifikationen von RNA, die zu einer erhöhten Transkriptstabilität und Translationseffizienz führen
US20070087437A1 (en) 2005-10-14 2007-04-19 Jifan Hu Methods for rejuvenating cells in vitro and in vivo
NZ568211A (en) 2005-11-04 2011-11-25 Novartis Vaccines & Diagnostic Influenza vaccines including combinations of particulate adjuvants and immunopotentiators
US20070105124A1 (en) 2005-11-08 2007-05-10 Getts Robert C Methods and kits for nucleic acid amplification
WO2007057167A2 (en) 2005-11-18 2007-05-24 Bioline Limited A method for enhancing enzymatic dna polymerase reactions
US10155816B2 (en) 2005-11-28 2018-12-18 Genmab A/S Recombinant monovalent antibodies and methods for production thereof
CA2639819C (en) 2005-11-30 2012-10-23 Epicentre Technologies Corporation Selective terminal tagging of nucleic acids
TWI389709B (zh) 2005-12-01 2013-03-21 Novartis Ag 經皮治療系統
US8603457B2 (en) 2005-12-02 2013-12-10 University Of Rochester Nonsense suppression and genetic codon alteration by targeted modification
WO2008051245A2 (en) 2005-12-02 2008-05-02 Novartis Ag Nanoparticles for use in immunogenic compositions
CA2632451C (en) 2005-12-06 2015-11-03 Centre National De La Recherche Scientifique Cell penetrating peptides for intracellular delivery of molecules
US7579318B2 (en) 2005-12-06 2009-08-25 Centre De La Recherche De La Scientifique Cell penetrating peptides for intracellular delivery of molecules
EP1960547A2 (en) 2005-12-08 2008-08-27 Novartis AG Effects of inhibitors of fgfr3 on gene transcription
EP1795599A1 (en) 2005-12-09 2007-06-13 Schuler, Gerold, Prof. Dr. Methods for generating antigen-specific effector T cells
US8048999B2 (en) 2005-12-13 2011-11-01 Kyoto University Nuclear reprogramming factor
AU2006325030B2 (en) 2005-12-16 2012-07-26 Cellectis Cell penetrating peptide conjugates for delivering nucleic acids into cells
EP1973493A2 (en) 2006-01-12 2008-10-01 Massachusetts Institute of Technology Biodegradable elastomers
DK1976871T3 (da) 2006-01-13 2011-12-12 Univ Pennsylvania Vacciner og immunterapeutika under anvendelse af codonoptimerede IL-15 og fremgangsmåder til anvendelse deraf
EP2526968A3 (en) 2006-01-27 2013-05-22 Biogen Idec MA Inc. Nogo receptor antagonists
EP1984381B1 (en) 2006-01-27 2010-09-29 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
US20070178103A1 (en) 2006-01-30 2007-08-02 Fey Georg H CD19-specific immunotoxin and treatment method
US8946155B2 (en) 2006-02-03 2015-02-03 Opko Biologics Ltd. Long-acting polypeptides and methods of producing and administering same
US9458444B2 (en) 2006-02-03 2016-10-04 Opko Biologics Ltd. Long-acting coagulation factors and methods of producing same
US8476234B2 (en) 2006-02-03 2013-07-02 Prolor Biotech Inc. Long-acting coagulation factors and methods of producing same
DE102006007433A1 (de) 2006-02-17 2007-08-23 Curevac Gmbh Adjuvanz in Form einer Lipid-modifizierten Nukleinsäure
KR100859972B1 (ko) 2006-02-20 2008-09-25 이화여자대학교 산학협력단 막투과 단백질 도메인 펩타이드
WO2007098466A2 (en) 2006-02-21 2007-08-30 Nektar Therapeutics Al, Corporation Segmented degradable polymers and conjugates made therefrom
AU2007221154A1 (en) 2006-02-24 2007-09-07 Novartis Ag Microparticles containing biodegradable polymer and cationic polysaccharide for use in immunogenic compositions
WO2007100789A2 (en) 2006-02-24 2007-09-07 Wyeth Gpat3 encodes a mammalian, microsomal acyl-coa:glycerol 3-phosphate acyltransferase
LT2676967T (lt) 2006-02-28 2019-09-10 Biogen Ma Inc. Uždegiminių ir autoimuninių ligų gydymo būdai su natalizumabu
US7910152B2 (en) 2006-02-28 2011-03-22 Advanced Cardiovascular Systems, Inc. Poly(ester amide)-based drug delivery systems with controlled release rate and morphology
GB0605217D0 (en) 2006-03-15 2006-04-26 Novartis Ag Method and compositions for assessing acute rejection
US8231907B2 (en) 2006-03-21 2012-07-31 Morehouse School Of Medicine Nanoparticles for delivery of active agents
ES2776100T3 (es) 2006-03-31 2020-07-29 Massachusetts Inst Technology Sistema para el suministro dirigido de agentes terapéuticos
WO2007123793A2 (en) 2006-04-04 2007-11-01 Stc.Unm Swellable particles for drug delivery
WO2007120863A2 (en) 2006-04-14 2007-10-25 Epicentre Technologies Kits and methods for generating 5' capped rna
EP1852127A1 (en) 2006-05-02 2007-11-07 Charité - Universitätsmedizin Berlin Use of a B-cell-depleting antibody for treatment of polyoma virus infections
EP2019691B1 (en) 2006-05-15 2020-08-12 Massachusetts Institute of Technology Polymers for functional particles
EA020805B1 (ru) 2006-05-24 2015-01-30 Мерк Сероно С.А. Применение комбинации кладрибина и бета-интерферона для лечения рассеянного склероза
EP2030015B1 (en) 2006-06-02 2016-02-17 President and Fellows of Harvard College Protein surface remodeling
WO2007149880A2 (en) * 2006-06-21 2007-12-27 Genentech, Inc. Crystal structure of ox40l and ox40l complexed with ox40 receptor
CA2656620C (en) 2006-07-04 2018-03-13 Genmab A/S Cd20 binding molecules for the treatment of copd
EP2295045A1 (en) 2006-07-07 2011-03-16 Aarhus Universitet Nanoparticles for nucleic acid delivery
ATE470681T1 (de) 2006-07-12 2010-06-15 Novartis Ag Aktinisch vernetzbare copolymere zur herstellung von kontaktlinsen
CA2658265A1 (en) 2006-07-20 2008-01-24 Novartis Ag Amigo-2 inhibitors for treating, diagnosing or detecting cancer
EP2054036B1 (en) 2006-07-24 2019-12-18 Singh-Broemer and Company, Inc. Solid nanoparticle formulation of water insoluble pharmaceutical substances with reduced ostwald ripening
US8304529B2 (en) * 2006-07-28 2012-11-06 Life Technologies Corporation Dinucleotide MRNA cap analogs
JP2010507361A (ja) 2006-07-31 2010-03-11 キュアバック ゲーエムベーハー 具体的には免疫刺激剤／アジュバントとしての、一般式（Ｉ）：ＧｌＸｍＧｎ、または一般式（ＩＩ）：ＣｌＸｍＣｎで表される核酸
DE102006035618A1 (de) 2006-07-31 2008-02-07 Curevac Gmbh Nukleinsäure der Formel (I): GlXmGn, insbesondere als immunstimulierendes Adjuvanz
BRPI0715393A2 (pt) 2006-08-07 2013-06-25 Genzyme Corp terapia de combinaÇço
AU2007284651B2 (en) 2006-08-09 2014-03-20 Institute For Systems Biology Organ-specific proteins and methods of their use
US8658211B2 (en) 2006-08-18 2014-02-25 Arrowhead Madison Inc. Polyconjugates for in vivo delivery of polynucleotides
EP2051965A2 (en) 2006-08-18 2009-04-29 Nastech Pharmaceutical Company Inc. Dicer substrate rna peptide conjugates and methods for rna therapeutics
JP5775260B2 (ja) 2006-09-06 2015-09-09 シー３ ジアン インコーポレイテッド 選択的に標的化された抗菌性ペプチドおよびその使用
EP2059532B1 (en) 2006-09-07 2012-12-26 Crucell Holland B.V. Human binding molecules capable of neutralizing influenza virus h5n1 and uses thereof
CA2663003C (en) 2006-09-08 2018-02-13 Justin Hanes Compositions and methods for enhancing transport through mucus
US8454948B2 (en) 2006-09-14 2013-06-04 Medgenics Medical Israel Ltd. Long lasting drug formulations
GB0619182D0 (en) 2006-09-29 2006-11-08 Leuven K U Res & Dev Oligonucleotide arrays
WO2008042973A2 (en) 2006-10-03 2008-04-10 Alnylam Pharmaceuticals, Inc. Lipid containing formulations
JP2010505877A (ja) 2006-10-05 2010-02-25 ザ・ジョンズ・ホプキンス・ユニバーシティー スマートな高分子ナノ粒子を用いた低水溶性薬物用の水分散性経口、非経口および局所的製剤
GB0619816D0 (en) * 2006-10-06 2006-11-15 Viragen Inc Novel interferon-alpha constructs for use in the treatment of cancer
DE102006051516A1 (de) 2006-10-31 2008-05-08 Curevac Gmbh (Basen-)modifizierte RNA zur Expressionssteigerung eines Proteins
US8414927B2 (en) 2006-11-03 2013-04-09 Boston Scientific Scimed, Inc. Cross-linked polymer particles
US7999087B2 (en) 2006-11-15 2011-08-16 Agilent Technologies, Inc. 2′-silyl containing thiocarbonate protecting groups for RNA synthesis
JP2010510236A (ja) 2006-11-15 2010-04-02 ダナ−ファーバー キャンサー インスティテュート インク． 安定化させたｍａｍｌペプチドおよびその使用法
US8242258B2 (en) 2006-12-03 2012-08-14 Agilent Technologies, Inc. Protecting groups for RNA synthesis
US8399007B2 (en) 2006-12-05 2013-03-19 Landec Corporation Method for formulating a controlled-release pharmaceutical formulation
AU2007330494B2 (en) 2006-12-06 2014-03-13 Seqirus UK Limited Vaccines including antigen from four strains of influenza virus
US9034348B2 (en) 2006-12-11 2015-05-19 Chi2Gel Ltd. Injectable chitosan mixtures forming hydrogels
UA116871C2 (uk) 2006-12-18 2018-05-25 Акселерон Фарма Інк. СПОСІБ ЛІКУВАННЯ МІЄЛОДИСПЛАСТИЧНОГО СИНДРОМУ, ТАЛАСЕМІЇ ТА СЕРПОПОДІБНО-КЛІТИННОЇ АНЕМІЇ ЗА ДОПОМОГОЮ ЗАСТОСУВАННЯ АНТАГОНІСТА АКТИВІНУ ПОЛІПЕПТИДУ ActRII
WO2008082563A2 (en) 2006-12-21 2008-07-10 Stryker Corporation Sustained-release formulations comprising crystals, macromolecular gels, and particulate suspensions of biologic agents
US8268586B2 (en) 2006-12-21 2012-09-18 Novozymes, Inc. Modified messenger RNA stabilizing sequences for expressing genes in bacterial cells
DE102006061015A1 (de) 2006-12-22 2008-06-26 Curevac Gmbh Verfahren zur Reinigung von RNA im präparativen Maßstab mittels HPLC
EP2207891B1 (en) 2006-12-22 2012-07-25 Archemix LLC Materials and methods for the generation of transcripts comprising modified nucleotides
US8338166B2 (en) 2007-01-04 2012-12-25 Lawrence Livermore National Security, Llc Sorting, amplification, detection, and identification of nucleic acid subsequences in a complex mixture
DE102007001370A1 (de) 2007-01-09 2008-07-10 Curevac Gmbh RNA-kodierte Antikörper
WO2008091799A2 (en) 2007-01-22 2008-07-31 The Trustees Of Columbia University In The City Of New York Cell-based methods for identifying inhibitors of parkinson's disease-associated lrrk2 mutants
ATE525392T1 (de) 2007-01-30 2011-10-15 Epivax Inc Regulatorische t-zellen-epitopen sowie zusammensetzungen damit und anwendungen davon
US8859229B2 (en) 2007-02-02 2014-10-14 Yale University Transient transfection with RNA
TW201940502A (zh) 2007-02-02 2019-10-16 美商艾瑟勒朗法瑪公司 衍生自ＡｃｔＲＩＩＢ的變體與其用途
WO2008096370A2 (en) 2007-02-05 2008-08-14 Natco Pharma Limited An efficient and novel purification method of recombinant hg-csf
US8333799B2 (en) 2007-02-12 2012-12-18 C. R. Bard, Inc. Highly flexible stent and method of manufacture
CA2689042A1 (en) 2007-02-16 2008-08-28 Merck & Co., Inc. Compositions and methods for potentiated activity of biologicaly active molecules
WO2008104294A1 (en) * 2007-02-27 2008-09-04 Bayer Schering Pharma Aktiengesellschaft Myh7 as a biomarker for ppara modulators
US8242087B2 (en) 2007-02-27 2012-08-14 K.U.Leuven Research & Development Phosphate modified nucleosides useful as substrates for polymerases and as antiviral agents
KR20100015363A (ko) 2007-03-02 2010-02-12 베링거 잉겔하임 파르마 게엠베하 운트 코 카게 단백질 생산의 개선
EP1964922A1 (en) 2007-03-02 2008-09-03 Boehringer Ingelheim Pharma GmbH & Co. KG Improvement of protein production
WO2008109712A2 (en) 2007-03-05 2008-09-12 Washington University Nanoparticle delivery systems for membrane-integrating peptides
EP2125892A2 (en) 2007-03-20 2009-12-02 Millennium Pharmaceuticals, Inc. Nucleic acids encoding humanized immunoglobulin that binds a4b7 integrin
BRPI0810969A2 (pt) 2007-04-27 2015-01-27 Echo Therapeutics Inc Dispositivo de permeação da pele para a detecção de analito ou liberação transdermal de fármaco
HRP20140789T1 (hr) 2007-04-30 2014-10-10 Glaxosmithkline Llc Postupci primjene protutijela protiv il-5
WO2008135855A2 (en) 2007-05-03 2008-11-13 Pfizer Products Inc. Nanoparticles comprising a cholesteryl ester transfer protein inhibitor and a nonionizable polymer
US7682789B2 (en) 2007-05-04 2010-03-23 Ventana Medical Systems, Inc. Method for quantifying biomolecules conjugated to a nanoparticle
CA2686735A1 (en) 2007-05-04 2008-11-13 Mdrna, Inc. Amino acid lipids and uses thereof
US8728491B2 (en) 2007-05-07 2014-05-20 Alba Therapeutics Corporation Transcutaneous delivery of therapeutic agents
JP5296328B2 (ja) 2007-05-09 2013-09-25 独立行政法人理化学研究所 １本鎖環状ｒｎａおよびその製造方法
HUE028389T2 (en) 2007-05-10 2016-12-28 Agilent Technologies Inc For the synthesis of thiocarbons protecting groups RNSS
ES2558689T3 (es) 2007-05-14 2016-02-08 Medimmune, Llc Métodos para reducir los niveles de eosinófilos
WO2008144365A2 (en) 2007-05-17 2008-11-27 Novartis Ag Method for making dry powder compositions containing ds-rna based on supercritical fluid technology
KR20100017169A (ko) 2007-05-22 2010-02-16 노파르티스 아게 Ｆｇｆ２１-관련 장애의 치료, 진단 및 검출 방법
CN101679978B (zh) 2007-05-22 2016-05-04 阿克丘勒斯治疗公司 羟甲基取代的rna寡核苷酸和rna复合物
MX2009013046A (es) 2007-05-30 2010-02-17 Univ Northwestern Nanoparticulas con grupo funcional de acido nucleico para aplicaciones terapeuticas.
JP2010528622A (ja) 2007-05-30 2010-08-26 ザ ジェネラル ホスピタル コーポレイション 体細胞から多能性細胞を生成する方法
CN104072561B (zh) 2007-06-19 2017-12-22 路易斯安那州州立大学及农业机械学院管理委员会 信使rna帽的抗‑反向硫代磷酸类似物的合成和用途
US8039214B2 (en) 2007-06-29 2011-10-18 Cellscript, Inc. Synthesis of tagged nucleic acids
US8367318B2 (en) 2007-07-23 2013-02-05 Dharmacon, Inc. Screening of micro-RNA cluster inhibitor pools
US20090042825A1 (en) 2007-08-06 2009-02-12 Majed Matar Composition, method of preparation & application of concentrated formulations of condensed nucleic acids with a cationic lipopolymer
US9144546B2 (en) 2007-08-06 2015-09-29 Clsn Laboratories, Inc. Nucleic acid-lipopolymer compositions
CN101835903A (zh) 2007-08-23 2010-09-15 诺瓦提斯公司 检测寡核苷酸的方法
WO2009030254A1 (en) 2007-09-04 2009-03-12 Curevac Gmbh Complexes of rna and cationic peptides for transfection and for immunostimulation
AU2008295140A1 (en) 2007-09-05 2009-03-12 F. Hoffmann-La Roche Ag Combination therapy with type I and type II anti-CD20 antibodies
US8506928B2 (en) 2007-09-07 2013-08-13 The Regents Of The University Of California Methods and compounds for targeting tissues
US20110086904A1 (en) 2007-09-17 2011-04-14 The Trustees Of The University Of Pennsylvania GENERATION OF HYPERSTABLE mRNAs
BRPI0817231B1 (pt) 2007-09-26 2020-06-09 Intrexon Corp vetor de expressão, método para expressar uma sequência de interesse em uma célula hospedeira e kit compreendendo o dito vetor
NZ584356A (en) 2007-09-26 2011-10-28 Univ Oregon Health & Science Cyclic undecapeptides and derivatives as multiple sclerosis therapies
ES2647538T3 (es) 2007-09-28 2017-12-22 Pfizer Inc. Direccionamiento a células de cáncer usando nanopartículas
EP2042193A1 (en) 2007-09-28 2009-04-01 Biomay AG RNA Vaccines
US8470560B2 (en) 2007-10-03 2013-06-25 The United States Of America As Represented By The Secretary Of The Army CR-2 binding peptide P28 as molecular adjuvant for DNA vaccines
WO2009046738A1 (en) 2007-10-09 2009-04-16 Curevac Gmbh Composition for treating lung cancer, particularly of non-small lung cancers (nsclc)
WO2009046739A1 (en) 2007-10-09 2009-04-16 Curevac Gmbh Composition for treating prostate cancer (pca)
MX350501B (es) 2007-10-12 2017-09-07 Massachusetts Inst Technology Nanotecnologia de vacuna.
US20090098118A1 (en) 2007-10-15 2009-04-16 Thomas Friess Combination therapy of a type ii anti-cd20 antibody with an anti-bcl-2 active agent
WO2009051451A2 (en) * 2007-10-17 2009-04-23 Korea Advanced Institute Of Science And Technology Ldl-like cationic nanoparticles for deliverying nucleic acid gene, method for preparing thereof and method for deliverying nucleic acid gene using the same
GB0720486D0 (en) * 2007-10-19 2007-11-28 Univ Edinburgh Cationic lipids
WO2009052830A1 (en) 2007-10-22 2009-04-30 Genmab A/S Novel antibody therapies
WO2009058911A2 (en) 2007-10-31 2009-05-07 Applied Biosystems Inc. Preparation and isolation of 5' capped mrna
CN104152489A (zh) 2007-11-01 2014-11-19 罗切斯特大学 具有增加的稳定性的重组因子viii
US20110002934A1 (en) 2007-11-09 2011-01-06 Novartis Ag Uses of anti-cd40 antibodies
WO2009062348A1 (en) 2007-11-14 2009-05-22 Institute Of Microbiology, Chinese Academy Of Sciences Methods for inhibiting influenza virus infection and their drugs
WO2009065600A2 (en) * 2007-11-21 2009-05-28 Technische Universität Dresden Means for treating myosin-related diseases
UY31504A1 (es) 2007-11-30 2009-07-17 Construcciones de union de antigenos
EP2848688A1 (en) 2007-12-10 2015-03-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of factor VII gene
WO2009075886A1 (en) 2007-12-11 2009-06-18 The Scripps Research Institute Compositions and methods related to mrna translational enhancer elements
WO2009076679A2 (en) 2007-12-13 2009-06-18 Alnylam Pharmaceuticals Inc. Methods and compositions for prevention or treatment of rsv infection
EP2072618A1 (en) 2007-12-14 2009-06-24 Johannes Gutenberg-Universität Mainz Use of RNA for reprogramming somatic cells
JP2011507897A (ja) 2007-12-21 2011-03-10 ジェネンテック， インコーポレイテッド リツキシマブ抵抗性関節リウマチ患者の治療
CA2709875C (en) * 2008-01-02 2019-07-16 Tekmira Pharmaceuticals Corporation Improved compositions and methods for the delivery of nucleic acids
JP5645044B2 (ja) 2008-01-22 2014-12-24 独立行政法人医薬基盤研究所 遺伝子発現制御機構を含む新規Ａｄベクター
CN102348806A (zh) 2008-01-23 2012-02-08 味之素株式会社 L-氨基酸的生产方法
JPWO2009093384A1 (ja) 2008-01-24 2011-05-26 独立行政法人産業技術総合研究所 ポリヌクレオチド及びポリヌクレオチド類似体並びにこれらを用いた遺伝子発現制御方法
EP3346005A1 (en) 2008-01-31 2018-07-11 CureVac AG Nucleic acids of formula (i) (nuglxmgnnv)a and derivatives thereof as an immunostimulating agent/adjuvant
US20100330677A1 (en) 2008-02-11 2010-12-30 Cambridge Enterprise Limited Improved Reprogramming of Mammalian Cells, and Cells Obtained
CA2726861C (en) 2008-02-13 2014-05-27 Intarcia Therapeutics, Inc. Devices, formulations, and methods for delivery of multiple beneficial agents
DE102008009920A1 (de) 2008-02-15 2009-08-20 Aj Innuscreen Gmbh Mobiles Gerät für die Nukleinsäureisolierung
US8506966B2 (en) 2008-02-22 2013-08-13 Novartis Ag Adjuvanted influenza vaccines for pediatric use
US20120027813A1 (en) 2008-02-22 2012-02-02 Novartis Vaccines And Diagnostics Srl Adjuvanted influenza vaccines for pediatric use
WO2009108891A2 (en) 2008-02-29 2009-09-03 Egen, Inc. Modified poloxamers for gene expression and associated methods
CN102027043A (zh) 2008-03-14 2011-04-20 艾根股份有限公司 生物可降解的交联支链聚(亚烷基亚胺)
EP2993186B1 (en) 2008-03-14 2019-09-04 Biocon Limited A monoclonal antibody and a method thereof
KR20100134702A (ko) 2008-03-28 2010-12-23 글락소스미스클라인 엘엘씨 치료 방법
CA2721333C (en) 2008-04-15 2020-12-01 Protiva Biotherapeutics, Inc. Novel lipid formulations for nucleic acid delivery
WO2009127230A1 (en) 2008-04-16 2009-10-22 Curevac Gmbh MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION
JP5539962B2 (ja) 2008-04-25 2014-07-02 ノースウェスタン、ユニバーシティ コレステロールを隔離するのに適したナノ構造体
AU2009243187C1 (en) 2008-04-28 2015-12-24 President And Fellows Of Harvard College Supercharged proteins for cell penetration
BRPI0913012B1 (pt) 2008-04-30 2021-12-14 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention Quimera de ácido nucleico, métodos para detectar um anticorpo do vírus da dengue em uma amostra de um paciente, e para produzir partículas virais que expressam proteínas prm e e do vírus da dengue, uso de vírus codificado pela quimera e flavivírus ou partícula viral quiméricos
US9394538B2 (en) 2008-05-07 2016-07-19 Shi-Lung Lin Development of universal cancer drugs and vaccines
EP2891501B1 (en) 2008-05-08 2016-09-21 MiniPumps, LLC Methods of manufacture of drug-delivery pumps
US8697098B2 (en) 2011-02-25 2014-04-15 South Dakota State University Polymer conjugated protein micelles
AU2009246327B8 (en) 2008-05-13 2013-10-03 Phaserx, Inc. Diblock copolymers and polynucleotide complexes thereof for delivery into cells
US9738680B2 (en) 2008-05-21 2017-08-22 Rheinische Friedrich-Wilhelms-Universität Bonn 5′ triphosphate oligonucleotide with blunt end and uses thereof
EP2772251B1 (en) 2008-05-26 2021-03-03 Universität Zürich Protamine/RNA nanoparticles for immunostimulation
EP2297197B1 (en) 2008-05-29 2012-03-07 HanAll Biopharma Co., Ltd. Modified erythropoietin (epo)polypeptides that exhibit increased protease resistance and pharmaceutical compositions thereof
FR2931824B1 (fr) 2008-05-29 2014-11-28 Centre Nat Rech Scient Procede de synthese d'arn par voie chimique.
US20100086922A1 (en) * 2008-05-30 2010-04-08 Millennium Pharmaceuticals, Inc. Assessment of chromosomal alterations to predict clinical outcome of bortezomib treatment
JP5715051B2 (ja) 2008-06-05 2015-05-07 イムノバクシーン・テクノロジーズ・インコーポレイテッドＩｍｍｕｎｏｖａｃｃｉｎｅ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｉｎｃ． リポソーム、抗原、ポリヌクレオチド及び疎水性物質の連続相を含む担体を含む組成物
PL215513B1 (pl) 2008-06-06 2013-12-31 Univ Warszawski Nowe boranofosforanowe analogi dinukleotydów, ich zastosowanie, czasteczka RNA, sposób otrzymywania RNA oraz sposób otrzymywania peptydów lub bialka
TWI451876B (zh) 2008-06-13 2014-09-11 Lilly Co Eli 聚乙二醇化之離脯胰島素化合物
US8613951B2 (en) 2008-06-16 2013-12-24 Bind Therapeutics, Inc. Therapeutic polymeric nanoparticles with mTor inhibitors and methods of making and using same
US8206747B2 (en) 2008-06-16 2012-06-26 Bind Biosciences, Inc. Drug loaded polymeric nanoparticles and methods of making and using same
WO2010005725A2 (en) 2008-06-16 2010-01-14 Bind Biosciences, Inc. Therapeutic polymeric nanoparticles comprising vinca alkaloids and methods of making and using same
DK2285350T3 (en) 2008-06-16 2017-12-11 Pfizer PROCEDURES FOR THE PREPARATION OF DIBLOCK COPOLYMERS FUNCTIONALIZED WITH TARGETING AGENT FOR USE IN THE MANUFACTURE OF THERAPEUTIC NANOPARTICLES
US9347088B2 (en) * 2008-06-27 2016-05-24 Institut Pasteur Molecular signature of liver tumor grade and use to evaluate prognosis and therapeutic regimen
PL2320925T3 (pl) * 2008-07-10 2016-06-30 Regenesance B V Antagoniści dopełniacza i ich zastosowania
US20100009424A1 (en) 2008-07-14 2010-01-14 Natasha Forde Sonoporation systems and methods
CA2730737A1 (en) 2008-07-15 2010-01-21 Novartis Ag Immunogenic amphipathic peptide compositions
WO2010009065A2 (en) 2008-07-15 2010-01-21 Novartis Ag Amphipathic peptide compositions
JP2011528910A (ja) * 2008-07-25 2011-12-01 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 センス鎖中の一般塩基またはミスマッチを使用したｓｉＲＮＡサイレンシング活性の亢進
US20110224447A1 (en) 2008-08-18 2011-09-15 Bowman Keith A Novel Lipid Nanoparticles and Novel Components for Delivery of Nucleic Acids
ES2413379T3 (es) * 2008-08-28 2013-07-16 Novartis Ag Presentación en la superficie celular de isoformas polipeptídicas mediante ultralectura de codón de terminación
WO2010025510A1 (en) 2008-09-03 2010-03-11 Xenome Ltd Libraries of peptide conjugates and methods for making them
US8309707B2 (en) 2008-09-06 2012-11-13 Chemgenes Corporation RNA synthesis-phosphoramidites for synthetic RNA in the reverse direction, and application in convenient introduction of ligands, chromophores and modifications of synthetic RNA at the 3′-end
US20120100558A1 (en) 2008-09-08 2012-04-26 Hanash Samir M Lung cancer diagnosis
WO2010030763A2 (en) 2008-09-10 2010-03-18 Bind Biosciences, Inc. High throughput fabrication of nanoparticles
TW201014605A (en) 2008-09-16 2010-04-16 Genentech Inc Methods for treating progressive multiple sclerosis
US20120021519A1 (en) 2008-09-19 2012-01-26 Presidents And Fellows Of Harvard College Efficient induction of pluripotent stem cells using small molecule compounds
US8962580B2 (en) * 2008-09-23 2015-02-24 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
WO2010037408A1 (en) 2008-09-30 2010-04-08 Curevac Gmbh Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof
WO2010042490A1 (en) 2008-10-06 2010-04-15 Boston Medical Center Corporation A single lentiviral vector system for induced pluripotent (ips) stem cells derivation
PL2350043T3 (pl) * 2008-10-09 2014-09-30 Tekmira Pharmaceuticals Corp Ulepszone aminolipidy i sposoby dostarczania kwasów nukleinowych
US8535655B2 (en) 2008-10-10 2013-09-17 Polyactiva Pty Ltd. Biodegradable polymer—bioactive moiety conjugates
US8343498B2 (en) 2008-10-12 2013-01-01 Massachusetts Institute Of Technology Adjuvant incorporation in immunonanotherapeutics
US8603532B2 (en) 2008-10-20 2013-12-10 Massachusetts Institute Of Technology Nanostructures for drug delivery
WO2010047839A1 (en) 2008-10-25 2010-04-29 Aura Biosciences Modified plant virus particles and uses therefor
WO2010053572A2 (en) 2008-11-07 2010-05-14 Massachusetts Institute Of Technology Aminoalcohol lipidoids and uses thereof
WO2010054406A1 (en) * 2008-11-10 2010-05-14 Alnylam Pharmaceuticals, Inc. Novel lipids and compositions for the delivery of therapeutics
CA2780482A1 (en) 2008-11-17 2010-05-10 Anil K. Sood Hdl particles for delivery of nucleic acids
EP2191840A1 (en) 2008-11-28 2010-06-02 Sanofi-Aventis Antitumor combinations containing antibodies recognizing specifically CD38 and melphalan
KR101073875B1 (ko) * 2008-11-28 2011-10-14 한국생명공학연구원 대장암 진단 마커 및 이를 이용한 대장암 진단방법
NZ593618A (en) 2008-12-10 2013-02-22 Alnylam Pharmaceuticals Inc Gnaq targeted dsrna compositions and methods for inhibiting expression
EP2196476A1 (en) 2008-12-10 2010-06-16 Novartis Ag Antibody formulation
WO2010068918A2 (en) 2008-12-12 2010-06-17 The Regents Of The University Of California Novel targets for treatment of hypercholesterolemia
US8563041B2 (en) 2008-12-12 2013-10-22 Bind Therapeutics, Inc. Therapeutic particles suitable for parenteral administration and methods of making and using same
ES2776126T3 (es) 2008-12-15 2020-07-29 Pfizer Nanopartículas de circulación prolongada para la liberación sostenida de agentes terapéuticos
WO2010080724A1 (en) 2009-01-12 2010-07-15 Merck Sharp & Dohme Corp. Novel lipid nanoparticles and novel components for delivery of nucleic acids
EA201170940A1 (ru) 2009-01-16 2012-02-28 ГЛЭКСОСМИТКЛАЙН ЭлЭлСи Лечение рака с использованием комбинации бендамустина и анти-cd20-антитела
WO2010084371A1 (en) 2009-01-26 2010-07-29 Mitoprod Novel circular interfering rna molecules
WO2010088537A2 (en) 2009-01-29 2010-08-05 Alnylam Pharmaceuticals, Inc. Improved lipid formulation
US8669085B2 (en) 2009-02-05 2014-03-11 Ut-Battelle, Llc Transformation of gram positive bacteria by sonoporation
WO2010088927A1 (en) 2009-02-09 2010-08-12 Curevac Gmbh Use of pei for the improvement of endosomal release and expression of transfected nucleic acids, complexed with cationic or polycationic compounds
US20140141089A1 (en) 2009-02-11 2014-05-22 Colorado School Of Mines Nanoparticles, Compositions Thereof, and Methods of Use, and Methods of Making the Same
WO2010098861A1 (en) 2009-02-24 2010-09-02 The Scripps Research Institute Reengineering mrna primary structure for enhanced protein production
WO2010141135A2 (en) 2009-03-05 2010-12-09 Trustees Of Boston University Bacteriophages expressing antimicrobial peptides and uses thereof
WO2010102066A1 (en) 2009-03-05 2010-09-10 Bend Research, Inc. Dextran polymer powder for inhalation administration of pharmaceuticals
US8714214B2 (en) 2009-03-12 2014-05-06 Illinois Tool Works Mis-fuel inhibitor
CA2755245A1 (en) 2009-03-13 2010-09-16 Egen, Inc. Compositions and methods for the delivery of biologically active rnas
US8460696B2 (en) 2009-03-20 2013-06-11 Egen, Inc. Polyamine derivatives
WO2010111290A1 (en) 2009-03-23 2010-09-30 University Of Utah Research Foundation Methods and compositions related to modified guanine bases for controlling off-target effects in rna interference
CA2756520C (en) 2009-03-24 2017-07-11 Council Of Scientific & Industrial Research Process for the preparation of agarose polymer from seaweed extractive
CN104722342B (zh) 2009-03-24 2017-01-11 芝加哥大学 滑动式芯片装置和方法
JP5622254B2 (ja) 2009-03-31 2014-11-12 国立大学法人東京大学 二本鎖リボ核酸ポリイオンコンプレックス
ES2784957T3 (es) 2009-04-03 2020-10-02 Univ Chicago Composiciones y métodos relacionados con variantes de la proteína A (SPA)
ES2683352T3 (es) 2009-04-13 2018-09-26 Inserm - Institut National De La Santé Et De La Recherche Médicale Partículas de HPV y usos de las mismas
MX2011010971A (es) 2009-04-17 2012-01-19 Biogen Idec Inc Composiciones y metodos para tratar leucemia mielogena aguda.
CA2759332A1 (en) 2009-04-21 2010-10-28 Selecta Biosciences, Inc. Immunonanotherapeutics providing a th1-biased response
EP2421563B1 (en) 2009-04-22 2017-04-12 Massachusetts Institute of Technology Innate immune suppression enables repeated delivery of long rna molecules
ES2655877T3 (es) 2009-04-27 2018-02-22 Novartis Ag Composiciones y métodos para aumentar el crecimiento muscular
US8287910B2 (en) 2009-04-30 2012-10-16 Intezyne Technologies, Inc. Polymeric micelles for polynucleotide encapsulation
US8715736B2 (en) 2009-04-30 2014-05-06 Florida Agricultural And Mechanical University Nanoparticle formulations for skin delivery
JP2012525415A (ja) 2009-05-01 2012-10-22 オプソテツク・コーポレイシヨン 眼科疾患を処置または予防するための方法
NZ711583A (en) 2009-05-05 2017-03-31 Arbutus Biopharma Corp Lipid compositions
DE202009007116U1 (de) 2009-05-18 2010-10-14 Amoena Medizin-Orthopädie-Technik GmbH Antidekubituskissen
EA022699B1 (ru) 2009-05-27 2016-02-29 Селекта Байосайенсиз, Инк. НАЦЕЛЕННЫЕ СИНТЕТИЧЕСКИЕ НАНОНОСИТЕЛИ С pH-ЧУВСТВИТЕЛЬНЫМ ВЫСВОБОЖДЕНИЕМ ИММУНОМОДУЛИРУЮЩИХ СРЕДСТВ
US8574835B2 (en) 2009-05-29 2013-11-05 Life Technologies Corporation Scaffolded nucleic acid polymer particles and methods of making and using
KR102066189B1 (ko) * 2009-06-10 2020-01-14 알닐람 파마슈티칼스 인코포레이티드 향상된 지질 조성물
EP2440556A1 (en) 2009-06-10 2012-04-18 Vertex Pharmaceuticals Incorporated Inhibitors of phosphatidylinositol 3-kinase
US8765370B2 (en) 2009-06-11 2014-07-01 Scinopharm Taiwan, Ltd Inhibition-based high-throughput screen strategy for cell clones
EA201270019A1 (ru) 2009-06-15 2012-06-29 Элнилэм Фармасьютикалз, Инк. Двуцепочечная рнк, включенная в липидный состав и мишенью которой является ген pcsk9
WO2010151664A2 (en) 2009-06-26 2010-12-29 Massachusetts Institute Of Technology Compositions and methods for treating cancer and modulating stress granule formation
JP5766188B2 (ja) 2009-07-01 2015-08-19 プロチバ バイオセラピューティクス インコーポレイティッド 固形腫瘍に治療剤を送達するための脂質製剤
US8569256B2 (en) 2009-07-01 2013-10-29 Protiva Biotherapeutics, Inc. Cationic lipids and methods for the delivery of therapeutic agents
US20110300205A1 (en) 2009-07-06 2011-12-08 Novartis Ag Self replicating rna molecules and uses thereof
DE102009033507A1 (de) * 2009-07-15 2011-01-20 Niro-Plan Ag Vorrichtung und Verfahren zum Erzeugen von gekühltem Kaffee
CN102473288A (zh) 2009-07-30 2012-05-23 皇家飞利浦电子股份有限公司 分布式图像重定向
EP3165234B1 (de) 2009-07-31 2019-04-03 ethris GmbH Rna mit einer kombination aus unmodifizierten und modifizierten nucleotiden zur proteinexpression
EP2281579A1 (en) 2009-08-05 2011-02-09 BioNTech AG Vaccine composition comprising 5'-Cap modified RNA
ES2579936T3 (es) 2009-08-20 2016-08-17 Sirna Therapeutics, Inc. Nuevos lípidos catiónicos con diversos grupos de cabeza para el suministro oligonucleotídico
US20110053829A1 (en) 2009-09-03 2011-03-03 Curevac Gmbh Disulfide-linked polyethyleneglycol/peptide conjugates for the transfection of nucleic acids
US20110070227A1 (en) 2009-09-18 2011-03-24 Anna-Marie Novotney-Barry Treatment of Autoimmune and Inflammatory Diseases
EP2485770A4 (en) 2009-10-08 2013-04-10 Merck Sharp & Dohme Novel cationic lipids with short lipid chains for oligonucleotide delivery
US8859284B2 (en) 2009-10-22 2014-10-14 The United States Of America, As Represented By The Secretary Of The Navy Delivery of nanoparticles to neurons
JP5823405B2 (ja) 2009-11-04 2015-11-25 ザ ユニバーシティ オブ ブリティッシュ コロンビア 核酸含有脂質粒子および関連方法
US8449916B1 (en) 2009-11-06 2013-05-28 Iowa State University Research Foundation, Inc. Antimicrobial compositions and methods
WO2011060250A1 (en) 2009-11-13 2011-05-19 Bend Research, Inc. Cationic dextran polymer derivatives
US9415113B2 (en) 2009-11-18 2016-08-16 University Of Washington Targeting monomers and polymers having targeting blocks
US8530429B2 (en) 2009-11-24 2013-09-10 Arch Cancer Therapeutics, Inc. Brain tumor targeting peptides and methods
RS58405B1 (sr) 2009-12-01 2019-04-30 Translate Bio Inc Stereoidni derivati za isporuku irnk u humanim genetskim oboljenjima
US20110245756A1 (en) 2009-12-03 2011-10-06 Rishi Arora Devices for material delivery, electroporation, sonoporation, and/or monitoring electrophysiological activity
DE102009056884B4 (de) 2009-12-03 2021-03-18 Novartis Ag Impfstoff-Adjuvantien und verbesserte Verfahren zur Herstellung derselben
AU2010325787B2 (en) 2009-12-06 2016-05-12 Bioverativ Therapeutics Inc. Factor VIII-Fc chimeric and hybrid polypeptides, and methods of use thereof
KR101878502B1 (ko) 2009-12-07 2018-07-13 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 세포 리프로그래밍을 위한 정제된 변형 ｒｎａ를 포함하는 ｒｎａ 제제
EP2509636B1 (en) 2009-12-07 2017-07-19 Arbutus Biopharma Corporation Compositions for nucleic acid delivery
US20130189741A1 (en) 2009-12-07 2013-07-25 Cellscript, Inc. Compositions and methods for reprogramming mammalian cells
WO2011069528A1 (en) 2009-12-09 2011-06-16 Curevac Gmbh Lyophilization of nucleic acids in lactate-containing solutions
WO2011069529A1 (en) 2009-12-09 2011-06-16 Curevac Gmbh Mannose-containing solution for lyophilization, transfection and/or injection of nucleic acids
TR201906255T4 (tr) 2009-12-11 2019-05-21 Pfizer Terapötik partiküllerin liyofilize edilmesine yönelik stabil formülasyonlar.
JP5898627B2 (ja) 2009-12-15 2016-04-06 バインド セラピューティックス インコーポレイテッド エポチロンを含む治療用ポリマーナノ粒子ならびにそれを製造および使用する方法
JP5965844B2 (ja) 2009-12-15 2016-08-10 バインド セラピューティックス インコーポレイテッド 高いガラス転移温度または高分子量のコポリマーを有する治療用ポリマーナノ粒子組成物
EP2512487A4 (en) 2009-12-15 2013-08-07 THERAPEUTIC POLYMERNANOPARTICLES WITH CORTICOSTEROIDS AND METHOD FOR THE PRODUCTION AND USE THEREOF
DE102009058769A1 (de) 2009-12-16 2011-06-22 MagForce Nanotechnologies AG, 10589 Temperaturabhängige Aktivierung von katalytischen Nukleinsäuren zur kontrollierten Wirkstofffreisetzung
WO2011084620A2 (en) 2009-12-16 2011-07-14 Brigham And Women's Hospital, Inc. Particles for multiple agent delivery
NZ600725A (en) 2009-12-18 2015-08-28 Univ British Colombia Methods and compositions for delivery of nucleic acids
EP2338520A1 (de) 2009-12-21 2011-06-29 Ludwig Maximilians Universität Konjugat mit Zielfindungsligand und dessen Verwendung
MX348474B (es) 2009-12-23 2017-06-14 Novartis Ag * Lipidos, composiciones de lipido, y metodos de uso de los mismos.
WO2011085231A2 (en) 2010-01-08 2011-07-14 Selecta Biosciences, Inc. Synthetic virus-like particles conjugated to human papillomavirus capsid peptides for use as vaccines
US8846631B2 (en) 2010-01-14 2014-09-30 Regulus Therapeutics Inc. MicroRNA compositions and methods
EP2525781A1 (en) 2010-01-22 2012-11-28 Schering Corporation Novel cationic lipids for oligonucleotide delivery
US20130101609A1 (en) 2010-01-24 2013-04-25 Novartis Ag Irradiated biodegradable polymer microparticles
EP2354247A1 (en) * 2010-02-11 2011-08-10 Academisch Medisch Centrum bij de Universiteit van Amsterdam Means and methods for typing a sample for rheumatoid arthritis or spondyloarthritis
RS54578B1 (sr) 2010-02-24 2016-06-30 Arrowhead Research Corporation Preparati za ciljano dopremanje sirnk
EP2538929A4 (en) 2010-02-25 2014-07-09 Univ Johns Hopkins DELAYED RELEASE OF THERAPIES IN A PART OF THE EYE
CN102884191B (zh) 2010-02-26 2018-04-27 凯杰有限公司 用于平行分离和/或纯化rna和dna的方法
US20110218170A1 (en) 2010-03-02 2011-09-08 Southern Research Institute Use of 2'-deoxy-4'-thiocytidine and its analogues as dna hypomethylating anticancer agents
US20130133483A1 (en) 2010-03-08 2013-05-30 University Of Rochester Synthesis of Nanoparticles Using Reducing Gases
AU2011227264A1 (en) 2010-03-16 2012-10-04 University Of Utah Research Foundation Cleavable modifications to reducible poly (amido ethylenimines)s to enhance nucleotide delivery
WO2011116072A1 (en) 2010-03-16 2011-09-22 Escape Therapeutics, Inc. Hybrid hydrogel scaffold compositions and methods of use
US20110230816A1 (en) 2010-03-18 2011-09-22 Tyco Healthcare Group Lp Gels for Transdermal Delivery
WO2011115862A1 (en) 2010-03-18 2011-09-22 Merck Sharp & Dohme Corp. Endosomolytic poly(amidoamine) disulfide polymers for the delivery of oligonucleotides
US9149432B2 (en) 2010-03-19 2015-10-06 Massachusetts Institute Of Technology Lipid vesicle compositions and methods of use
GB201005005D0 (en) 2010-03-25 2010-05-12 Angeletti P Ist Richerche Bio New vaccine
CA2794307A1 (en) 2010-03-26 2011-09-29 Mersana Therapeutics, Inc. Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof
US8207290B2 (en) 2010-03-26 2012-06-26 Cerulean Pharma Inc. Methods and systems for generating nanoparticles
US20110247090A1 (en) 2010-04-02 2011-10-06 Intrexon Corporation Synthetic 5'UTRs, Expression Vectors, and Methods for Increasing Transgene Expression
EP2555794A4 (en) 2010-04-05 2014-01-15 Univ Chicago COMPOSITIONS AND METHODS RELATING TO PROTEIN A (SPA) ANTIBODIES AS IMMUNE REACTION AMPLIFIERS
BR112012025364A2 (pt) 2010-04-07 2015-09-22 Novartis Ag método para geração de partícula semelhante a vírus de parvovírus b19
EP2558074B1 (en) 2010-04-08 2018-06-06 The Trustees of Princeton University Preparation of lipid nanoparticles
CA2795695A1 (en) 2010-04-09 2011-10-13 The University Of Tokyo Microrna-controlled recombinant vaccinia virus and use thereof
CN104922071A (zh) 2010-04-09 2015-09-23 帕西拉制药有限公司 用于配制大直径合成膜囊泡的方法
US20110262491A1 (en) 2010-04-12 2011-10-27 Selecta Biosciences, Inc. Emulsions and methods of making nanocarriers
KR101196667B1 (ko) 2010-04-15 2012-11-02 포항공과대학교 산학협력단 피에이치 민감성 금속 나노 입자를 이용한 항암제 전달 시스템
EP2377938A1 (en) 2010-04-16 2011-10-19 Eukarys Capping-prone RNA polymerase enzymes and their applications
US11225655B2 (en) 2010-04-16 2022-01-18 Nuevolution A/S Bi-functional complexes and methods for making and using such complexes
CA2796464C (en) 2010-04-16 2021-08-03 Immune Disease Institute, Inc. Sustained polypeptide expression from synthetic, modified rnas and uses thereof
US20130260460A1 (en) 2010-04-22 2013-10-03 Isis Pharmaceuticals Inc Conformationally restricted dinucleotide monomers and oligonucleotides
EP3540055A1 (en) 2010-04-23 2019-09-18 University of Massachusetts Cns targeting aav vectors and methods of use thereof
US9586044B2 (en) 2010-04-28 2017-03-07 Kimberly-Clark Worldwide, Inc. Method for increasing the permeability of an epithelial barrier
WO2011139911A2 (en) 2010-04-29 2011-11-10 Isis Pharmaceuticals, Inc. Lipid formulated single stranded rna
BR112012027816A2 (pt) 2010-04-30 2017-08-08 Novartis Ag marcadores preditivos úteis no tratamento da síndrome do x frágil (fxs).
WO2011143230A1 (en) 2010-05-10 2011-11-17 Alnylam Pharmaceuticals Methods and compositions for delivery of active agents
WO2011141704A1 (en) 2010-05-12 2011-11-17 Protiva Biotherapeutics, Inc Novel cyclic cationic lipids and methods of use
JP2013527856A (ja) 2010-05-12 2013-07-04 プロチバ バイオセラピューティクス インコーポレイティッド 陽イオン性脂質およびその使用方法
EP2387999A1 (en) 2010-05-21 2011-11-23 CureVac GmbH Histidine-containing solution for transfection and/or injection of nucleic acids and uses thereof
EP2575895A2 (en) 2010-05-24 2013-04-10 Merck Sharp & Dohme Corp. Novel amino alcohol cationic lipids for oligonucleotide delivery
CN106177940A (zh) 2010-05-26 2016-12-07 西莱克塔生物科技公司 含有佐剂的合成纳米载体的剂量选择
SG186085A1 (en) 2010-06-03 2013-01-30 Alnylam Pharmaceuticals Inc Biodegradable lipids for the delivery of active agents
EP2575767B1 (en) 2010-06-04 2017-01-04 Sirna Therapeutics, Inc. Novel low molecular weight cationic lipids for oligonucleotide delivery
RU2556800C2 (ru) 2010-06-14 2015-07-20 Ф.Хоффманн-Ля Рош Аг Пептиды, проникающие в клетки, и их применения
US20130236968A1 (en) 2010-06-21 2013-09-12 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
CA2803239A1 (en) 2010-06-25 2011-12-29 Novartis Ag Combinations of meningococcal factor h binding proteins
JP5635690B2 (ja) 2010-07-01 2014-12-03 ポステック アカデミー‐インダストリー ファウンデーション 細菌由来マイクロベシクルを用いた癌治療及び癌診断方法
KR101130137B1 (ko) 2010-07-02 2012-03-28 연세대학교 산학협력단 발광다이오드 모듈
BR112013000097B1 (pt) 2010-07-02 2022-02-01 The University Of Chicago Polipeptídeo imunogênico isolado, composição imunogênica e seu uso
WO2012004276A2 (en) * 2010-07-06 2012-01-12 Fondazione Telethon Multiprotein biomarkers of amyotrophic lateral sclerosis in peripheral blood mononuclear cells, diagnostic methods and kits
HUE026646T2 (en) 2010-07-06 2016-07-28 Glaxosmithkline Biologicals Sa Preferred liposomes containing lipids of PKA value for delivery of RNA
ES2586580T3 (es) 2010-07-06 2016-10-17 Glaxosmithkline Biologicals Sa Inmunización de mamíferos grandes con dosis bajas de ARN
RU2625546C2 (ru) 2010-07-06 2017-07-14 Новартис Аг Катионные эмульсии "масло-в-воде"
US9770463B2 (en) 2010-07-06 2017-09-26 Glaxosmithkline Biologicals Sa Delivery of RNA to different cell types
ES2646669T3 (es) 2010-07-06 2017-12-14 Glaxosmithkline Biologicals Sa Procedimientos de aumento de una respuesta inmunitaria mediante el suministro de ARN
US9192661B2 (en) 2010-07-06 2015-11-24 Novartis Ag Delivery of self-replicating RNA using biodegradable polymer particles
HRP20161352T1 (hr) 2010-07-06 2016-12-02 Glaxosmithkline Biologicals Sa Čestice nalik na virione za unos samoreplicirajućih molekula rna
US9611310B2 (en) 2010-07-09 2017-04-04 Bioverativ Therapeutics Inc. Systems for factor VIII processing and methods thereof
NZ605348A (en) 2010-07-09 2015-01-30 Biogen Idec Hemophilia Inc Factor ix polypeptides and methods of use thereof
US20130177523A1 (en) 2010-07-13 2013-07-11 University Of Utah Research Foundation Gold particles and methods of making and using the same in cancer treatment
GB201012410D0 (en) 2010-07-23 2010-09-08 Medical Res Council Intracellular immunity
DE102010032758B4 (de) 2010-07-29 2012-02-23 Fujitsu Technology Solutions Intellectual Property Gmbh Computersystem, Verfahren zum Programmieren einer Echtzeituhr und Computerprogrammprodukt
ES2558106T3 (es) 2010-07-30 2016-02-02 Curevac Ag Formación de complejos de ácidos nucleicos con componentes catiónicos disulfuro-reticulados para la transfección e inmunoestimulación
US20130190626A1 (en) 2010-08-02 2013-07-25 Curtin University Of Technology Determining location of, and imaging, a subsurface boundary
US8822663B2 (en) * 2010-08-06 2014-09-02 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
WO2012021516A2 (en) 2010-08-09 2012-02-16 The Trustees Of The University Of Pennsylvania Nanoparticle-oligonucletide hybrid structures and methods of use thereof
WO2012019630A1 (en) 2010-08-13 2012-02-16 Curevac Gmbh Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded protein
US8829329B2 (en) 2010-08-18 2014-09-09 International Business Machines Corporation Solar cell and battery 3D integration
EP2605799A4 (en) 2010-08-20 2014-02-26 Cerulean Pharma Inc CONJUGATES, PARTICLES, COMPOSITIONS AND RELATED METHODS
US20120058153A1 (en) 2010-08-20 2012-03-08 Selecta Biosciences, Inc. Synthetic nanocarrier vaccines comprising proteins obtained or derived from human influenza a virus hemagglutinin
WO2012024595A2 (en) 2010-08-20 2012-02-23 University Of Washington Circumferential aerosol device for delivering drugs to olfactory epithelium and brain
AU2011290471B2 (en) 2010-08-20 2015-08-20 Novartis Ag Soluble needle arrays for delivery of influenza vaccines
PL3556396T3 (pl) 2010-08-31 2022-09-12 Theraclone Sciences, Inc. Przeciwciała neutralizujące ludzki wirus niedoboru odporności (hiv)
KR20130100278A (ko) 2010-08-31 2013-09-10 머크 샤프 앤드 돔 코포레이션 올리고뉴클레오티드의 전달을 위한 신규 단일 화학 존재물 및 방법
DK4226941T3 (da) 2010-08-31 2024-12-02 Glaxosmithkline Biologicals Sa Pegylerede liposomer til levering af immunogen-kodende rna
CN103384515B (zh) 2010-08-31 2017-02-15 诺华有限公司 适用于脂质体递送编码蛋白质的rna的脂质
EP4043040B1 (en) 2010-08-31 2023-01-11 GlaxoSmithKline Biologicals SA Small liposomes for delivery of immunogen-encoding rna
WO2012031205A2 (en) 2010-09-03 2012-03-08 The Brigham And Women's Hospital, Inc. Lipid-polymer hybrid particles
US20130236419A1 (en) 2010-09-09 2013-09-12 The University Of Chicago Compositions and methods related to attenuated staphylococcal strains
EP2614074A1 (en) 2010-09-09 2013-07-17 The University of Chicago Methods and compositions involving protective staphylococcal antigens
US10307372B2 (en) 2010-09-10 2019-06-04 The Johns Hopkins University Rapid diffusion of large polymeric nanoparticles in the mammalian brain
US8466122B2 (en) 2010-09-17 2013-06-18 Protiva Biotherapeutics, Inc. Trialkyl cationic lipids and methods of use thereof
WO2012040184A2 (en) 2010-09-20 2012-03-29 Merck Sharp & Dohme Corp. Novel low molecular weight cationic lipids for oligonucleotide delivery
US20130183718A1 (en) 2010-09-21 2013-07-18 RibpxX GmbH Method for Synthesizing RNA using DNA Template
JP2013540757A (ja) 2010-09-24 2013-11-07 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 カプセル化された作用物質の放出を制御する能力を有するナノ構造ゲル
WO2012050975A2 (en) 2010-09-29 2012-04-19 The University Of North Carolina At Chapel Hill Novel circular mammalian rna molecules and uses thereof
EP2621480B1 (en) 2010-09-30 2018-08-15 Sirna Therapeutics, Inc. Low molecular weight cationic lipids for oligonucleotide delivery
CA2821992A1 (en) 2010-10-01 2012-04-05 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
WO2013086505A1 (en) 2011-12-09 2013-06-13 Vanderbilt University Integrated organ-on-chip system and applications of the same
US8898864B1 (en) 2010-10-08 2014-12-02 David Porter Integrated rockably released leverage snap fastening system
KR102266691B1 (ko) 2010-10-11 2021-06-23 노파르티스 아게 항원 전달 플랫폼
WO2012051220A1 (en) 2010-10-11 2012-04-19 Wichita State University Composite magnetic nanoparticle drug delivery system
US9029590B2 (en) 2010-10-21 2015-05-12 Sirna Therapeutics, Inc. Low molecular weight cationic lipids for oligonucleotide delivery
WO2012054923A2 (en) 2010-10-22 2012-04-26 Bind Biosciences, Inc. Therapeutic nanoparticles with high molecular weight copolymers
WO2012154202A1 (en) 2010-10-29 2012-11-15 Merck Sharp & Dohme Corp. Recombinant subunit dengue virus vaccine
EP2635254B1 (en) 2010-11-05 2019-05-15 The John Hopkins University Compositions and methods relating to reduced mucoadhesion
WO2012061259A2 (en) 2010-11-05 2012-05-10 Merck Sharp & Dohme Corp. Novel low molecular weight cyclic amine containing cationic lipids for oligonucleotide delivery
KR20130139254A (ko) 2010-11-09 2013-12-20 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 피부 침투 및 세포 진입（ｓｐａｃｅ） 펩타이드 및 그의 사용방법
MX346784B (es) 2010-11-12 2017-03-31 Inovio Pharmaceuticals Inc Antigenos prostaticos de consenso, molecula de acido nucleico que los codifica y vacuna y usos que los comprenden.
MX344972B (es) 2010-11-16 2017-01-12 Selecta Biosciences Inc Oligonucleotidos inmunoestimulantes.
SMT201800444T1 (it) 2010-11-17 2018-09-13 Aduro Biotech Inc Metodi e composizioni per indurre una risposta immunitaria contro egfrviii
US20140053294A1 (en) * 2010-11-19 2014-02-20 The University Of Queensland Pongamia Genetic Markers and Method of Use
WO2012068187A1 (en) 2010-11-19 2012-05-24 Merck Sharp & Dohme Corp. Poly(amide) polymers for the delivery of oligonucleotides
US8486908B2 (en) 2010-11-19 2013-07-16 Idera Pharmaceuticals, Inc. Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response
WO2012075040A2 (en) 2010-11-30 2012-06-07 Shire Human Genetic Therapies, Inc. mRNA FOR USE IN TREATMENT OF HUMAN GENETIC DISEASES
WO2012072096A1 (en) 2010-12-03 2012-06-07 Biontech Ag Method for cellular rna expression
AU2011358150B2 (en) 2010-12-16 2016-11-03 Sprna Gmbh Pharmaceutical composition consisting of RNA having alkali metal as counter ion and formulated with dications
US8901101B2 (en) 2010-12-17 2014-12-02 Sirna Therapeutics, Inc. Membrane lytic poly(amido amine) polymers for the delivery of oligonucleotides
US8501930B2 (en) 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
CA2825370A1 (en) 2010-12-22 2012-06-28 President And Fellows Of Harvard College Continuous directed evolution
WO2012089225A1 (en) 2010-12-29 2012-07-05 Curevac Gmbh Combination of vaccination and inhibition of mhc class i restricted antigen presentation
CN103282503B (zh) 2010-12-29 2015-12-02 弗·哈夫曼-拉罗切有限公司 用于细胞内递送核酸的小分子缀合物
WO2012092552A1 (en) 2010-12-30 2012-07-05 Selecta Biosciences, Inc. Synthetic nanocarriers with reactive groups that release biologically active agents
CA2862765A1 (en) 2011-01-04 2012-07-12 Brown University Nanotubes as carriers of nucleic acids into cells
WO2012094574A2 (en) 2011-01-06 2012-07-12 The Johns Hopkins University Stabilized polyribonucleotide nanoparticles
US20140080766A1 (en) 2011-01-07 2014-03-20 Massachusetts Institute Of Technology Compositions and methods for macromolecular drug delivery
US9999673B2 (en) 2011-01-11 2018-06-19 Alnylam Pharmaceuticals, Inc. PEGylated lipids and their use for drug delivery
DE102011002640B4 (de) 2011-01-13 2021-10-07 Evonik Operations Gmbh Verfahren zur Aufreinigung von Biphephos
US20120189700A1 (en) 2011-01-19 2012-07-26 Zoraida Aguilar Nanoparticle Based Immunological Stimulation
EP2667898A1 (en) 2011-01-26 2013-12-04 Cenix Bioscience GmbH Delivery system and conjugates for compound delivery via naturally occurring intracellular transport routes
US10363309B2 (en) 2011-02-04 2019-07-30 Case Western Reserve University Targeted nanoparticle conjugates
US20140066363A1 (en) 2011-02-07 2014-03-06 Arun K. Bhunia Carbohydrate nanoparticles for prolonged efficacy of antimicrobial peptide
WO2012116715A1 (en) 2011-03-02 2012-09-07 Curevac Gmbh Vaccination in newborns and infants
US20120207840A1 (en) 2011-02-10 2012-08-16 Aura Biosciences, Inc. Virion Derived Protein Nanoparticles For Delivering Diagnostic Or Therapeutic Agents For The Treatment Of Non-Melanoma Skin Cancer
WO2012112582A2 (en) 2011-02-14 2012-08-23 Swift Biosciences, Inc. Polynucleotide primers and probes
US20140081012A1 (en) 2011-02-15 2014-03-20 The University Of North Carolina At Chapel Hill Nanoparticle, liposomes, polymers, agents and proteins modified with reversible linkers
EP2675918B1 (en) 2011-02-15 2017-11-08 Merrimack Pharmaceuticals, Inc. Compositions and methods for delivering nucleic acid to a cell
EP2489371A1 (en) 2011-02-18 2012-08-22 Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria Carrier peptides for drug delivery
WO2012113413A1 (en) 2011-02-21 2012-08-30 Curevac Gmbh Vaccine composition comprising complexed immunostimulatory nucleic acids and antigens packaged with disulfide-linked polyethyleneglycol/peptide conjugates
CN103492574B (zh) 2011-02-22 2015-12-09 加州理工学院 使用腺相关病毒（aav）载体递送蛋白
US8696637B2 (en) 2011-02-28 2014-04-15 Kimberly-Clark Worldwide Transdermal patch containing microneedles
WO2012116714A1 (en) 2011-03-02 2012-09-07 Curevac Gmbh Vaccination in elderly patients
TR201811280T4 (tr) 2011-03-02 2018-08-27 Glaxosmithkline Biologicals Sa Düşük antijen ve/ veya adjuvan dozları olan karma aşılar.
CA2832807A1 (en) 2011-03-07 2012-09-13 Massachusetts Institute Of Technology Methods for transfecting cells with nucleic acids
US20120237565A1 (en) 2011-03-14 2012-09-20 Intezyne Technologies, Incorporated Pegylated polyplexes containing two or more different polymers for polynucleotide delivery
WO2012125680A1 (en) 2011-03-16 2012-09-20 Novartis Ag Methods of treating vasculitis using an il-17 binding molecule
RU2013146242A (ru) 2011-03-17 2015-04-27 Новартис Аг Fgfr и его лиганды в качестве биомаркеров рака молочной железы у hr-положительных индивидуумов
US20140212503A1 (en) 2011-03-17 2014-07-31 Hyukjin Lee Delivery system
ES2785108T3 (es) 2011-03-24 2020-10-05 Glaxosmithkline Biologicals Sa Nanoemulsiones adyuvantes con fosfolípidos
CA2830948A1 (en) 2011-03-25 2012-10-04 Selecta Biosciences, Inc. Osmotic mediated release synthetic nanocarriers
WO2012129648A1 (en) 2011-03-25 2012-10-04 University Of Guelph Enhancing protein expression of adeno-associated virus vectors
US20140005070A1 (en) 2011-03-28 2014-01-02 Novartis Ag Markers associated with cyclin-dependent kinase inhibitors
CA2831392C (en) 2011-03-28 2020-04-28 Massachusetts Institute Of Technology Conjugated lipomers and uses thereof
CA2831469C (en) 2011-03-31 2020-02-18 Ingell Technologies Holding B.V. Biodegradable compositions suitable for controlled release
AU2012237262A1 (en) 2011-03-31 2013-11-14 Ingell Technologies Holding B.V. Biodegradable compositions suitable for controlled release
CN103764169B (zh) 2011-03-31 2017-06-13 康斯坦策·沙费尔 用于非病毒转移核酸的全氟化化合物
DE12722942T1 (de) 2011-03-31 2021-09-30 Modernatx, Inc. Freisetzung und formulierung von manipulierten nukleinsäuren
AU2012237456B2 (en) * 2011-04-01 2017-06-29 Universitat Stuttgart Recombinant TNF ligand family member polypeptides with antibody binding domain and uses thereof
US10086043B2 (en) 2011-04-03 2018-10-02 The General Hospital Corporation Efficient protein expression in vivo using modified RNA (MOD-RNA)
EP2694524B1 (en) 2011-04-04 2016-05-18 The U.S.A. As Represented By The Secretary, Department Of Health And Human Services 2'-o-aminooxymethyl nucleoside derivatives for use in the synthesis and modification of nucleosides, nucleotides and oligonucleotides
WO2012142132A1 (en) 2011-04-11 2012-10-18 Life Technologies Corporation Polymer particles and methods of making and using same
WO2012142240A1 (en) 2011-04-13 2012-10-18 The Trustees Of The University Of Pennsylvania Coated mesoporous nanoparticles
WO2013158127A1 (en) 2012-04-16 2013-10-24 Molecular Transfer, Inc. Agents for improved delivery of nucleic acids to eukaryotic cells
US20140178894A1 (en) 2011-04-20 2014-06-26 Novartis Forschungsstiftung, Zweigniederlassung Culture medium suitable for the culture of undifferentiated cells
CA2834349A1 (en) 2011-04-26 2012-11-01 Molecular Express, Inc. Liposomal formulations
US10647959B2 (en) 2011-04-27 2020-05-12 President And Fellows Of Harvard College Cell-friendly inverse opal hydrogels for cell encapsulation, drug and protein delivery, and functional nanoparticle encapsulation
US20160272697A2 (en) 2011-04-28 2016-09-22 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Neutralizing Antibodies to Nipah and Hendra Virus
EP2701686A4 (en) 2011-04-28 2014-11-05 Stc Unm LIPID BINCHES SUPPORTED ON POROUS NANOPARTICLES (PROTOCELLS) FOR TARGETED ADMINISTRATION, AND METHODS OF USE THEREOF
AU2012249553A1 (en) 2011-04-29 2013-10-24 Selecta Biociences, Inc. Tolerogenic synthetic nanocarriers for allergy therapy
US20120283503A1 (en) 2011-04-29 2012-11-08 The Johns Hopkins University Nanoparticle loaded stem cells and their use in mri guided hyperthermia
EP2702408A1 (en) 2011-04-29 2014-03-05 Novartis AG Methods of treating squamous cell carcinoma related applications
UA116189C2 (uk) 2011-05-02 2018-02-26 Мілленніум Фармасьютікалз, Інк. КОМПОЗИЦІЯ АНТИ-α4β7 АНТИТІЛА
WO2012151234A2 (en) 2011-05-02 2012-11-08 Wayne State University A protein-induced pluripotent cell technology uses thereof
EP3409112B1 (en) 2011-05-04 2022-07-27 The University of Nottingham Novel polymers which resist bacterial attachment
US9327029B2 (en) 2011-05-05 2016-05-03 Celacare Technologies, Llc Antimicrobial silver hydrogel composition for the treatment of burns and wounds
US8945588B2 (en) 2011-05-06 2015-02-03 The University Of Chicago Methods and compositions involving protective staphylococcal antigens, such as EBH polypeptides
WO2012152810A1 (de) 2011-05-10 2012-11-15 Basf Se Öl-in-wasser-emulsionen
CN103687624B (zh) 2011-05-11 2018-02-02 雷蒙特亚特特拉维夫大学有限公司 靶向的聚合缀合物和其用途
DK2706988T3 (da) 2011-05-12 2020-01-20 Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd Liposomer omfattende polymer konjugerede lipider og relateret brug
CA2835492A1 (en) 2011-05-12 2012-11-15 Helmut Vockner Novel pharmaceutical formulation
WO2012158613A1 (en) 2011-05-13 2012-11-22 Novartis Ag Pre-fusion rsv f antigens
US8691750B2 (en) 2011-05-17 2014-04-08 Axolabs Gmbh Lipids and compositions for intracellular delivery of biologically active compounds
US20140206752A1 (en) 2011-05-17 2014-07-24 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof for non-human vertebrates
WO2012162174A1 (en) 2011-05-20 2012-11-29 Kohler Co. Toilet installation system and method
HRP20230443T1 (hr) 2011-05-24 2023-09-15 BioNTech SE Individualizirana cjepiva protiv raka
PL2714926T3 (pl) 2011-05-25 2015-12-31 Novartis Ag Biomarkery raka płuca
US20120302940A1 (en) 2011-05-26 2012-11-29 Jackson State University Popcorn Shape Gold Nanoparticle For Targeted Diagnosis, Photothermal Treatment and In-Situ Monitoring Therapy Response for Cancer and Multiple Drug Resistance Bacteria
US20140308363A1 (en) 2011-05-31 2014-10-16 Bind Therapeutics, Inc. Drug loaded polymeric nanoparticles and methods of making and using same
DK2714017T3 (en) 2011-06-02 2018-09-03 Univ California MEMBRANE-WRAPPED NANOPARTICLES AND METHOD OF USE
CN104975099A (zh) 2011-06-02 2015-10-14 诺华股份有限公司 Hedgehog抑制剂治疗的生物标志物
WO2012168259A1 (en) 2011-06-06 2012-12-13 Novartis Forschungsstiftung, Zweigniederlassung Protein tyrosine phosphatase, non-receptor type 11 (ptpn11) and triple-negative breast cancer
JP6184945B2 (ja) 2011-06-08 2017-08-23 シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド ｍＲＮＡ送達のための脂質ナノ粒子組成物および方法
ES2987057T3 (es) 2011-06-08 2024-11-13 Translate Bio Inc Lípidos escindibles
WO2012168491A1 (en) 2011-06-10 2012-12-13 Novartis Ag Pharmaceutical formulations of pcsk9 antagonists
WO2012170607A2 (en) 2011-06-10 2012-12-13 Novartis Ag Use of pcsk9 antagonists
US8636696B2 (en) 2011-06-10 2014-01-28 Kimberly-Clark Worldwide, Inc. Transdermal device containing microneedles
US9364527B2 (en) 2011-06-10 2016-06-14 Novartis Tiergesundheit Ag Bovine vaccines and methods
US8916696B2 (en) 2011-06-12 2014-12-23 City Of Hope Aptamer-mRNA conjugates for targeted protein or peptide expression and methods for their use
WO2012172495A1 (en) 2011-06-14 2012-12-20 Novartis Ag Compositions and methods for antibodies targeting tem8
HK1197039A1 (zh) 2011-06-15 2015-01-02 Chrontech Pharma Ab 注射针和装置
MX2013014789A (es) 2011-06-16 2014-01-20 Novartis Ag Proteinas solubles para utilizarse como productos terapeuticos.
KR20140047069A (ko) 2011-06-20 2014-04-21 유니버시티 오브 피츠버그 - 오브 더 커먼웰쓰 시스템 오브 하이어 에듀케이션 계산에 최적화된 광범위 반응을 나타내는 ｈ１ｎ１ 인플루엔자를 위한 항원
US9862926B2 (en) 2011-06-27 2018-01-09 Cellscript, Llc. Inhibition of innate immune response
KR102171142B1 (ko) 2011-06-28 2020-10-28 이노비오 파마수티컬즈, 인크. 최소 침습 피부 전기천공 장치
DK2726099T3 (en) 2011-07-01 2018-11-05 Novartis Ag Method of treating metabolic disorders
AU2012278910A1 (en) 2011-07-04 2014-01-16 Commonwealth Scientific And Industrial Research Organisation Nucleic acid complex
EP2729168A2 (en) 2011-07-06 2014-05-14 Novartis AG Immunogenic compositions and uses thereof
AU2012280901B2 (en) 2011-07-06 2016-11-10 Glaxosmithkline Biologicals S.A. Oil-in-water emulsions that contain nucleic acids
RU2649133C2 (ru) 2011-07-06 2018-03-29 Новартис Аг Катионные эмульсии масло-в-воде
CN103764121A (zh) 2011-07-06 2014-04-30 诺华股份有限公司 用于递送rna分子的具有有用n:p比的脂质体
US11896636B2 (en) 2011-07-06 2024-02-13 Glaxosmithkline Biologicals Sa Immunogenic combination compositions and uses thereof
EP2729501A2 (en) 2011-07-07 2014-05-14 Life Technologies Corporation Polymer particles, nucleic acid polymer particles and methods of making and using the same
US20130012566A1 (en) 2011-07-10 2013-01-10 Aura Biosciences, Inc. Virion Derived Protein Nanoparticles For Delivering Diagnostic Or Therapeutic Agents For The Treatment of Alopecia
US9617392B2 (en) 2011-07-10 2017-04-11 President And Fellows Of Harvard College Compositions and methods for self-assembly of polymers with complementary macroscopic and microscopic scale units
WO2013009717A1 (en) 2011-07-10 2013-01-17 Elisabet De Los Pinos Virion derived protein nanoparticles for delivering diagnostic or therapeutic agents for the treatment of skin-related diseases
GB2492999A (en) 2011-07-20 2013-01-23 Univ Central Lancashire Neutron detector
US20140148503A1 (en) 2011-07-20 2014-05-29 University Of Iowa Research Foundation Nucleic acid aptamers
CN103732211B (zh) 2011-07-21 2017-03-01 禾大国际股份公开有限公司 支化的聚醚‑聚酰胺嵌段共聚物及其制造与使用方法
ES2687129T3 (es) 2011-07-25 2018-10-23 Glaxosmithkline Biologicals Sa Composiciones y métodos para evaluar la inmunogenicidad funcional de vacunas contra parvovirus
US9493549B2 (en) 2011-07-25 2016-11-15 The Rockefeller University Antibodies directed toward the HIV-1 GP120 CD4 binding site with increased potency and breadth
KR20140050698A (ko) 2011-07-29 2014-04-29 셀렉타 바이오사이언시즈, 인크. 체액성 및 세포독성 t 림프구(ctl) 면역 반응을 발생시키는 합성 나노운반체
CN103906535B (zh) 2011-08-15 2017-07-14 芝加哥大学 与葡萄球菌蛋白a的抗体相关的组合物和方法
CN104024328A (zh) 2011-08-26 2014-09-03 箭头研究公司 用于体内核酸递送的聚(乙烯基酯)聚合物
JP2014527071A (ja) 2011-08-31 2014-10-09 マリンクロッド エルエルシー Ｈ−ホスホネートによるナノ粒子ｐｅｇの改変
US20140255472A1 (en) 2011-08-31 2014-09-11 Andrew Geall Pegylated liposomes for delivery of immunogen-encoding rna
US9126966B2 (en) 2011-08-31 2015-09-08 Protiva Biotherapeutics, Inc. Cationic lipids and methods of use thereof
WO2013033620A1 (en) 2011-09-01 2013-03-07 Irm Llc Compounds and compositions as pdgfr kinase inhibitors
JP2014525435A (ja) 2011-09-02 2014-09-29 ノバルティス アーゲー Ｈｓｆ１関連疾患を処置するための有機組成物
EP3384938A1 (en) 2011-09-12 2018-10-10 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
EP2755986A4 (en) * 2011-09-12 2015-05-20 Moderna Therapeutics Inc MANIPULATED NUCLEIC ACIDS AND METHOD OF APPLICATION THEREFOR
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
WO2013038375A2 (en) 2011-09-14 2013-03-21 Novartis Ag Methods for making saccharide-protein glycoconjugates
SG11201400527XA (en) 2011-09-16 2014-04-28 Univ Pennsylvania Rna engineered t cells for the treatment of cancer
US20150017245A1 (en) 2011-09-22 2015-01-15 Bind Therapeutics, Inc. Methods of treating cancers with therapeutic nanoparticles
US9375388B2 (en) 2011-09-23 2016-06-28 Indian Institute Of Technology, Bombay Nanoparticle based cosmetic composition
TWI593708B (zh) 2011-09-26 2017-08-01 諾華公司 治療代謝病症之融合蛋白質
US9458214B2 (en) 2011-09-26 2016-10-04 Novartis Ag Dual function fibroblast growth factor 21 proteins
WO2013049328A1 (en) 2011-09-27 2013-04-04 Alnylam Pharmaceuticals, Inc. Di-aliphatic substituted pegylated lipids
US9951349B2 (en) 2011-09-27 2018-04-24 Yale University Compositions and methods for transient expression of recombinant RNA
WO2013045505A1 (en) 2011-09-28 2013-04-04 Novartis Ag Biomarkers for raas combination therapy
HRP20220250T1 (hr) 2011-10-03 2022-04-29 Modernatx, Inc. Modificirani nukleozidi, nukleotidi i nukleinske kiseline, te njihove uporabe
GB201117279D0 (en) * 2011-10-06 2011-11-16 Nexeon Ltd Etched silicon structures, method of forming etched silicon structures and uses thereof
CA2872033A1 (en) 2011-10-11 2013-04-18 Novartis Ag Recombinant self-replicating polycistronic rna molecules
WO2013055971A1 (en) 2011-10-11 2013-04-18 Arizona Board Of Regents For And On Behalf Of Arizona State University Polymers for delivering a substance into a cell
US12371522B2 (en) 2011-10-12 2025-07-29 The Johns Hopkins University Bioreducible poly (beta-amino ester)s for siRNA delivery
EP2766407B1 (en) 2011-10-12 2018-06-27 The Curators Of The University Of Missouri Pentablock polymers
US8673184B2 (en) * 2011-10-13 2014-03-18 Flexcon Company, Inc. Systems and methods for providing overcharge protection in capacitive coupled biomedical electrodes
ES2769786T3 (es) 2011-10-14 2020-06-29 Recordati Ag Anticuerpos y métodos para enfermedades relacionadas con la vía Wnt
AU2012323937A1 (en) 2011-10-14 2014-06-05 Stc.Unm Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery including transdermal delivery of cargo and methods thereof
JP2015501178A (ja) 2011-10-18 2015-01-15 ミセル テクノロジーズ，インク． 薬物送達のための医療用デバイス
CA2852917C (en) 2011-10-18 2020-07-07 Dicerna Pharmaceuticals, Inc. Amine cationic lipids and uses thereof
AU2012324398A1 (en) 2011-10-20 2014-05-01 Seqirus UK Limited Adjuvanted influenza B virus vaccines for pediatric priming
CA3083244C (en) 2011-10-20 2023-01-03 Novartis Ag Biomarkers predictive of responsiveness to alpha 7 nicotinic acetylcholine receptor activator treatment
WO2013059922A1 (en) 2011-10-25 2013-05-02 The University Of British Columbia Limit size lipid nanoparticles and related methods
US20130110043A1 (en) 2011-10-26 2013-05-02 Nanopass Technologies Ltd. Microneedle Intradermal Drug Delivery Device with Auto-Disable Functionality
CN104039382B (zh) 2011-10-27 2018-01-12 金伯利-克拉克环球有限公司 高粘度生物活性剂的经皮递送
PE20181541A1 (es) 2011-10-27 2018-09-26 Massachusetts Inst Technology Derivados de aminoacidos funcionalizados en la terminal n capaces de formar microesferas encapsuladoras de farmaco
SG10201508662SA (en) 2011-10-28 2015-11-27 Presage Biosciences Inc Methods for drug delivery
WO2013062140A1 (en) 2011-10-28 2013-05-02 Kyoto University Method for efficiently inducing differentiation of pluripotent stem cells into hepatic lineage cells
AU2012328524B2 (en) 2011-10-28 2017-05-18 Excelse Bio, Inc. Protein formulations containing amino acids
EP3424564A1 (en) 2011-10-31 2019-01-09 Mallinckrodt LLC Combinational liposome compositions for cancer therapy
KR102259829B1 (ko) 2011-10-31 2021-06-03 제넨테크, 인크. 항체 제제
US9579338B2 (en) 2011-11-04 2017-02-28 Nitto Denko Corporation Method of producing lipid nanoparticles for drug delivery
US9872870B2 (en) 2011-11-04 2018-01-23 University Of Notre Dame Du Lac Multifunctional micellar nanoparticle-based drug and targeting agent system
SG11201401964TA (en) 2011-11-04 2014-05-29 Agency Science Tech & Res Self-assembled composite ultrasmall peptide-polymer hydrogels
JP2015502741A (ja) 2011-11-04 2015-01-29 ノバルティス アーゲー 低比重リポタンパク質関連タンパク質６（ｌｒｐ６）−半減期延長構築物
CN103906504B (zh) 2011-11-04 2017-11-17 日东电工株式会社 制备用于药物递送的脂质纳米颗粒的方法
US20130116408A1 (en) 2011-11-05 2013-05-09 Aura Biosciences, Inc. Virion Derived Protein Nanoparticles For Delivering Radioisotopes For The Diagnosis And Treatment Of Malignant And Systemic Disease And The Monitoring Of Therapy
US20130115247A1 (en) 2011-11-05 2013-05-09 Aura Biosciences, Inc. Virion Derived Protein Nanoparticles For Delivering Radioisotopes For The Diagnosis And Treatment Of Malignant And Systemic Disease And The Monitoring Of Therapy
EP2776838A1 (en) 2011-11-08 2014-09-17 Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute For Biomedical Research Early diagnostic of neurodegenerative diseases
EP2776459A1 (en) 2011-11-08 2014-09-17 Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute For Biomedical Research Rod cell-specific promoter
WO2013068431A1 (en) 2011-11-08 2013-05-16 Novartis Forschungsstiftung, Zweigniederlassung, Friedrich Miescher Institute For Biomedical Research New treatment for neurodegenerative diseases
WO2013070872A1 (en) 2011-11-08 2013-05-16 The Board Of Trustees Of The University Of Arkansas Methods and compositions for x-ray induced release from ph sensitive liposomes
WO2013070653A1 (en) 2011-11-09 2013-05-16 Board Of Trustees Michigan State University Metallic nanoparticle synthesis with carbohydrate capping agent
CN111995664B (zh) 2011-11-11 2024-08-02 变异生物技术公司 用于治疗巨细胞病毒的组合物和方法
WO2013071047A1 (en) 2011-11-11 2013-05-16 Children's Medical Center Corporation Compositions and methods for in vitro transcription of rna
EP2780035A1 (en) 2011-11-14 2014-09-24 Novartis AG Immunogenic complexes of polyanionic carbomers and env polypeptides and methods of manufacture and use thereof
US20140343128A1 (en) 2011-11-15 2014-11-20 Novartis Ag Combination of a phosphoinositide 3-kinase inhibitor and a modulator of the Janus Kinase 2 - Signal Transducer and Activator of Transcription 5 pathway
PT3574897T (pt) 2011-11-18 2022-04-06 Regeneron Pharma Formulação de libertação prolongada compreendendo micropartículas de proteína polimérica para utilização no vítreo do olho para o tratamento de distúrbios oculares vasculares
AU2012341081B2 (en) 2011-11-21 2015-06-04 Novartis Ag Methods of treating psoriatic arthritis (PsA) using IL-17 antagonists and PsA response or non- response alleles
WO2013078199A2 (en) 2011-11-23 2013-05-30 Children's Medical Center Corporation Methods for enhanced in vivo delivery of synthetic, modified rnas
JP2015504563A (ja) * 2011-11-23 2015-02-12 プロテウス デジタル ヘルス， インコーポレイテッド マインドフルネス技法に基づいて行動変容を促進するデバイス、システム、および方法
US8930541B2 (en) * 2011-11-25 2015-01-06 International Business Machines Corporation System, method and program product for cost-aware selection of templates for provisioning shared resources
EP2786337A4 (en) * 2011-11-28 2015-08-26 Expanergy Llc METHODS AND SYSTEMS OF AN ENERGY SEARCH ENGINE
CN103136247B (zh) * 2011-11-29 2015-12-02 阿里巴巴集团控股有限公司 属性数据区间划分方法及装置
WO2013082111A2 (en) 2011-11-29 2013-06-06 The University Of North Carolina At Chapel Hill Geometrically engineered particles and methods for modulating macrophage or immune responses
WO2013082418A1 (en) 2011-11-30 2013-06-06 3M Innovative Properties Company Microneedle device having a peptide therapeutic agent and an amino acid, methods of making and using the same
US9364549B2 (en) 2011-11-30 2016-06-14 Andreas Voigt Hydrophobic drug-delivery material, method for manufacturing thereof and methods for delivery of a drug-delivery composition
DE102011087509A1 (de) * 2011-12-01 2013-06-06 Robert Bosch Gmbh Sensorübertragungsvorrichtung und Verfahren zur Übertragung von Nutzdaten von einer Mehrzahl von Sensoren an eine Bussteuervorrichtung für ein Fahrzeug
US20130142781A1 (en) 2011-12-02 2013-06-06 Invivo Therapeutics Corporation Peg based hydrogel for peripheral nerve injury applications and compositions and method of use of synthetic hydrogel sealants
WO2013082529A1 (en) 2011-12-02 2013-06-06 Yale University Enzymatic synthesis of poly(amine-co-esters) and methods of use thereof for gene delivery
EP2785333A4 (en) 2011-12-02 2015-04-01 Pegasus Lab Inc AMPHIPATIVE COMPOSITIONS WITH DELAYED RELIEF ON LIPID BASIS
MX354995B (es) 2011-12-05 2018-03-27 Factor Bioscience Inc Metodos y productos para transfeccion de celulas.
JP6564187B2 (ja) 2011-12-05 2019-08-21 ナノ プレシジョン メディカル インコーポレイテッドＮａｎｏ Ｐｒｅｃｉｓｉｏｎ Ｍｅｄｉｃａｌ， Ｉｎｃ． チタニアナノチューブ膜を有する、薬物送達用デバイス
US8497124B2 (en) 2011-12-05 2013-07-30 Factor Bioscience Inc. Methods and products for reprogramming cells to a less differentiated state
WO2013086373A1 (en) 2011-12-07 2013-06-13 Alnylam Pharmaceuticals, Inc. Lipids for the delivery of active agents
CA2856737C (en) 2011-12-07 2023-09-26 Alnylam Pharmaceuticals, Inc. Branched alkyl and cycloalkyl terminated biodegradable lipids for the delivery of active agents
GB201121070D0 (en) 2011-12-07 2012-01-18 Isis Innovation composition for delivery of biotherapeutics
HK1200089A1 (en) 2011-12-07 2015-07-31 Alnylam Pharmaceuticals, Inc. Biodegradable lipids for the delivery of active agents
US9725687B2 (en) 2011-12-09 2017-08-08 President And Fellows Of Harvard College Integrated human organ-on-chip microphysiological systems
WO2013086502A1 (en) 2011-12-09 2013-06-13 President And Fellows Of Harvard College Organ chips and uses thereof
EP2787977A4 (en) 2011-12-09 2015-05-06 Univ California LIPOSOMAL ACTIVE INVERTING
CA2858694A1 (en) 2011-12-12 2013-06-20 Kyowa Hakko Kirin Co., Ltd. Lipid nano particles comprising combination of cationic lipids
US9839616B2 (en) 2011-12-12 2017-12-12 Kyowa Hakko Kirin Co., Ltd. Lipid nano particles comprising cationic lipid for drug delivery system
CA2858884A1 (en) 2011-12-12 2013-06-20 The Trustees Of The University Of Pennsylvania Proteins comprising mrsa pbp2a and fragments thereof, nucleic acids encoding the same, and compositions and their use to prevent and treat mrsa infections
US20150000936A1 (en) 2011-12-13 2015-01-01 Schlumberger Technology Corporation Energization of an element with a thermally expandable material
EP2604253A1 (en) 2011-12-13 2013-06-19 Otto Glatter Water-in-oil emulsions and methods for their preparation
US9844598B2 (en) 2011-12-13 2017-12-19 Engeneic Molecular Delivery Pty Ltd Bacterially derived, intact minicells for delivery of therapeutic agents to brain tumors
EP2791364A4 (en) 2011-12-14 2015-11-11 Moderna Therapeutics Inc PROCESS FOR RESPONSE TO A BIOLOGICAL THREAT
EP2791159A4 (en) 2011-12-14 2015-10-14 Moderna Therapeutics Inc MODIFIED NUCLEIC ACIDS AND ACUTE TREATMENT USES THEREOF
US20140349320A1 (en) 2011-12-15 2014-11-27 The Trustees Of The University Of Pennsylvania Using Adaptive Immunity to Detect Drug Resistance
US9636414B2 (en) 2011-12-15 2017-05-02 Biontech Ag Particles comprising single stranded RNA and double stranded RNA for immunomodulation
AU2012351967A1 (en) 2011-12-16 2014-07-17 Massachusetts Institute Of Technology Alpha-aminoamidine polymers and uses thereof
WO2013087912A1 (en) 2011-12-16 2013-06-20 Synthon Biopharmaceuticals B.V. Compounds and methods for treating inflammatory diseases
SI2791160T1 (sl) 2011-12-16 2022-07-29 Modernatx, Inc. Sestave modificirane MRNA
WO2013090841A2 (en) 2011-12-16 2013-06-20 Novartis Ag Aerosolization apparatus for inhalation profile-independent drug delivery
WO2013090601A2 (en) 2011-12-16 2013-06-20 Massachusetts Institute Of Technology Compact nanoparticles for biological applications
KR20140103168A (ko) 2011-12-16 2014-08-25 알러간, 인코포레이티드 폴리비닐 카프라락탐-폴리비닐 아세테이트-폴리에틸렌 글리콜 그라프트 코폴리머를 포함하는 안과 조성물
WO2013091001A1 (en) 2011-12-19 2013-06-27 The University Of Sydney A peptide-hydrogel composite
US9241829B2 (en) 2011-12-20 2016-01-26 Abbott Medical Optics Inc. Implantable intraocular drug delivery apparatus, system and method
RU2014129863A (ru) * 2011-12-21 2016-02-10 Модерна Терапьютикс, Инк. Способы повышения жизнеспособности или увеличения продолжительности жизни органа или экспланта органа
US20130195851A1 (en) 2011-12-23 2013-08-01 Genentech, Inc. Articles of manufacture and methods for co-administration of antibodies
US10814115B2 (en) 2011-12-27 2020-10-27 Massachusetts Institute Of Technology Microneedle devices and uses thereof
US10596246B2 (en) 2011-12-29 2020-03-24 Glaxosmithkline Biological Sa Adjuvanted combinations of meningococcal factor H binding proteins
WO2013101690A1 (en) 2011-12-29 2013-07-04 modeRNA Therapeutics Modified mrnas encoding cell-penetrating polypeptides
AU2012362113B2 (en) 2011-12-30 2017-08-03 Cellscript, Llc Making and using in vitro-synthesized ssRNA for introducing into mammalian cells to induce a biological or biochemical effect
MX367352B (es) 2012-01-06 2019-08-16 Gemphire Therapeutics Inc Metodos para reducir el riesgo de padecer una enfermedad cardiovascular.
WO2013106496A1 (en) 2012-01-10 2013-07-18 modeRNA Therapeutics Methods and compositions for targeting agents into and across the blood-brain barrier
CN104220588A (zh) 2012-01-26 2014-12-17 生命科技公司 用于提高病毒感染性的方法
EP2807252B1 (en) 2012-01-26 2017-05-10 Life Technologies Corporation Methods for increasing the infectivity of viruses
WO2013113326A1 (en) 2012-01-31 2013-08-08 Curevac Gmbh Pharmaceutical composition comprising a polymeric carrier cargo complex and at least one protein or peptide antigen
EP2623121A1 (en) 2012-01-31 2013-08-07 Bayer Innovation GmbH Pharmaceutical composition comprising a polymeric carrier cargo complex and an antigen
WO2013113325A1 (en) 2012-01-31 2013-08-08 Curevac Gmbh Negatively charged nucleic acid comprising complexes for immunostimulation
KR102081560B1 (ko) 2012-02-09 2020-02-25 라이프 테크놀로지스 코포레이션 친수성 중합체성 입자 및 그의 제조 방법
WO2013120497A1 (en) * 2012-02-15 2013-08-22 Curevac Gmbh Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded therapeutic protein
WO2013126564A1 (en) 2012-02-22 2013-08-29 Cerulean Pharma Inc. Conjugates, particles, compositions, and related methods
US20130243867A1 (en) 2012-02-23 2013-09-19 University Of South Florida (A Florida Non-Profit Corporation) Micelle compositions and methods for their use
US20130224268A1 (en) 2012-02-27 2013-08-29 Newgen Biopharma Corp. Topical delivery of hormonal and non hormonal nano formulations, methods of making and using the same
MX353382B (es) 2012-03-01 2018-01-10 Amgen Res Munich Gmbh Moleculas de union polipeptido de larga duracion.
WO2013136234A1 (en) 2012-03-13 2013-09-19 University Of Kwazulu-Natal Transdermal delivery devices
US10322089B2 (en) 2012-03-14 2019-06-18 The Board Of Trustees Of The Leland Stanford Junior University Nanoparticles, nanoparticle delivery methods, and systems of delivery
WO2013135359A1 (en) 2012-03-16 2013-09-19 Merck Patent Gmbh Targeting aminoacid lipids
US8962577B2 (en) 2012-03-16 2015-02-24 The Johns Hopkins University Controlled release formulations for the delivery of HIF-1 inhibitors
EP2825207B1 (en) 2012-03-16 2020-08-19 The Johns Hopkins University Non-linear multiblock copolymer-drug conjugates for the delivery of active agents
CN103325662B (zh) 2012-03-21 2016-03-30 清华大学 半导体性单壁碳纳米管的制备方法
US9610346B2 (en) 2012-03-23 2017-04-04 International Aids Vaccine Initiative Recombinant viral vectors
WO2013142349A1 (en) 2012-03-23 2013-09-26 University Of Chicago Compositions and methods related to staphylococcal sbi
US9717685B2 (en) 2012-03-26 2017-08-01 President And Fellows Of Harvard College Lipid-coated nucleic acid nanostructures of defined shape
WO2013143555A1 (en) 2012-03-26 2013-10-03 Biontech Ag Rna formulation for immunotherapy
SG10201607962RA (en) 2012-03-27 2016-11-29 Curevac Ag Artificial nucleic acid molecules
WO2013148541A1 (en) 2012-03-27 2013-10-03 Merck Sharp & Dohme Corp. DIETHER BASED BIODEGRADABLE CATIONIC LIPIDS FOR siRNA DELIVERY
AU2013242404B2 (en) 2012-03-27 2018-08-30 CureVac SE Artificial nucleic acid molecules for improved protein or peptide expression
SG11201405545XA (en) 2012-03-27 2014-11-27 Curevac Gmbh Artificial nucleic acid molecules comprising a 5'top utr
EP3865123A1 (en) 2012-03-29 2021-08-18 Translate Bio, Inc. Lipid-derived neutral nanoparticles
HK1206612A1 (en) * 2012-04-02 2016-01-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of secreted proteins
US9283287B2 (en) * 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US20140275229A1 (en) 2012-04-02 2014-09-18 Moderna Therapeutics, Inc. Modified polynucleotides encoding udp glucuronosyltransferase 1 family, polypeptide a1
US20150050354A1 (en) 2012-04-02 2015-02-19 Moderna Therapeutics, Inc. Modified polynucleotides for the treatment of otic diseases and conditions
US10501513B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
US10501512B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides
AU2013243952A1 (en) 2012-04-02 2014-10-30 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
EP2833926A4 (en) 2012-04-05 2015-11-25 Univ Florida NEUROPHILIC NANOPARTICLES
EP3563872A1 (en) 2012-04-05 2019-11-06 Massachusetts Institute Of Technology Immunostimulatory compositions and methods of use thereof
WO2013152351A2 (en) 2012-04-06 2013-10-10 The Trustees Of Columbia University In The City Of New York Fusion polypeptides and methods of use thereof
EP2836200B1 (en) 2012-04-08 2020-07-15 Urogen Pharma Ltd. Reverse thermal hydrogel preparations for use in the treatment of disorders of the urothelium
CN106511270A (zh) 2012-04-11 2017-03-22 茵肽锌科技公司 用于稳定的胶束的嵌段共聚物
US9610250B2 (en) 2012-04-12 2017-04-04 Yale University Nanolipogel vehicles for controlled delivery of different pharmaceutical agents
WO2013155513A1 (en) 2012-04-13 2013-10-17 President And Fellows Of Harvard College Devices and methods for in vitro aerosol delivery
WO2013154766A1 (en) 2012-04-13 2013-10-17 New York University Microrna control of ldl receptor pathway
BR112014004528A2 (pt) 2012-04-18 2019-09-24 Arrowhead Res Corp polímeros de poli(acrilato) para entrega de ácido nucleico in vivo
JP6232416B2 (ja) 2012-04-19 2017-11-15 サーナ・セラピューティクス・インコーポレイテッドＳｉｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． オリゴヌクレオチド送達のための、新規なジエステルおよびトリエステルベースの低分子量、生分解性カチオン性脂質
WO2013163234A1 (en) 2012-04-23 2013-10-31 Massachusetts Institute Of Technology Stable layer-by-layer coated particles
NZ630591A (en) 2012-04-25 2017-02-24 Regulus Therapeutics Inc Microrna compounds and methods for modulating mir-21 activity
WO2013166385A1 (en) 2012-05-03 2013-11-07 Kala Pharmaceuticals, Inc. Pharmaceutical nanoparticles showing improved mucosal transport
HK1208377A1 (en) 2012-05-04 2016-03-04 The Johns Hopkins University Lipid-based drug carriers for rapid penetration through mucus linings
WO2013173657A1 (en) 2012-05-16 2013-11-21 Micell Technologies, Inc. Low burst sustained release lipophilic and biologic agent compositions
WO2013173582A1 (en) 2012-05-17 2013-11-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Hepatitis c virus neutralizing antibody
WO2013173693A1 (en) 2012-05-18 2013-11-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Nanoparticles with enhanced entry into cancer cells
BR112014027834A2 (pt) 2012-05-23 2017-08-08 Univ Ohio State composições de nanopartícula lipídica para entrega de oligonucleotídeos antissenso
EP2854857B1 (en) 2012-05-25 2018-11-28 CureVac AG Reversible immobilization and/or controlled release of nucleic acid containing nanoparticles by (biodegradable) polymer coatings
AU2013271548B2 (en) 2012-06-06 2017-05-25 Loma Vista Medical, Inc. Inflatable medical devices
PT3489220T (pt) 2012-06-08 2021-10-22 Nitto Denko Corp Lípidos para formulações de administração de agentes terapêuticos
EP3800254A1 (en) 2012-06-08 2021-04-07 Ethris GmbH Pulmonary delivery of messenger rna
BR112014030677A2 (pt) 2012-06-08 2022-07-19 Shire Human Genetic Therapies distribuição pulmonar de mrna para células-alvo não-pulmonares
US20140005379A1 (en) 2012-06-20 2014-01-02 Frank GU Nanoparticle delivery system and components thereof
WO2014014613A2 (en) 2012-06-20 2014-01-23 President And Fellows Of Harvard College Self-assembling peptides, peptide nanostructures and uses thereof
WO2014004436A2 (en) 2012-06-27 2014-01-03 Merck Sharp & Dohme Corp. Crystalline anti-human il-23 antibodies
US9150841B2 (en) 2012-06-29 2015-10-06 Shire Human Genetic Therapies, Inc. Cells for producing recombinant iduronate-2-sulfatase
US9956291B2 (en) 2012-07-10 2018-05-01 Shaker A. Mousa Nanoformulation and methods of use of thyroid receptor beta1 agonists for liver targeting
EP2872120B1 (en) 2012-07-16 2017-05-03 Nanoderm Sciences, Inc. Therapeutic nanoparticles with a polymyxin b as targeting agent
EP2687252A1 (en) 2012-07-17 2014-01-22 Sanofi-Aventis Deutschland GmbH Drug delivery device
EP2687251A1 (en) 2012-07-17 2014-01-22 Sanofi-Aventis Deutschland GmbH Drug delivery device
CN112587658A (zh) 2012-07-18 2021-04-02 博笛生物科技有限公司 癌症的靶向免疫治疗
WO2014015334A1 (en) 2012-07-20 2014-01-23 Brown University System and methods for nanostructure protected delivery of treatment agent and selective release thereof
US10604543B2 (en) 2012-07-24 2020-03-31 President And Fellows Of Harvard College Self-assembly of nucleic acid nanostructures
GB201213624D0 (en) 2012-07-27 2012-09-12 Univ Ulster The Method and system for production of conjugated nanoparticles
WO2014015422A1 (en) 2012-07-27 2014-01-30 Ontario Institute For Cancer Research Cellulose-based nanoparticles for drug delivery
WO2014024193A1 (en) 2012-08-07 2014-02-13 Prodel Pharma Ltd. Compositions and methods for rapid transmucosal delivery of pharmaceutical ingredients
WO2014025795A1 (en) 2012-08-07 2014-02-13 Northeastern University Compositions for the delivery of rna and drugs into cells
WO2014026044A2 (en) 2012-08-08 2014-02-13 Presage Biosciences, Inc. Extrusion methods and devices for drug delivery
SG10201700973YA (en) 2012-08-08 2017-04-27 Univ Nanyang Tech Methods of manufacturing hydrogel microparticles having living cells, and compositions for manufacturing a scaffold for tissue engineering
JP2015525799A (ja) 2012-08-10 2015-09-07 ユニバーシティ・オブ・ノース・テキサス・ヘルス・サイエンス・センターＵｎｉｖｅｒｓｉｔｙ ｏｆ Ｎｏｒｔｈ Ｔｅｘａｓ Ｈｅａｌｔｈ Ｓｃｉｅｎｃｅ Ｃｅｎｔｅｒ ターゲティングポリアミノ酸および脂肪酸のコンジュゲートを含む薬物送達ビークル
WO2014028487A1 (en) 2012-08-13 2014-02-20 Massachusetts Institute Of Technology Amine-containing lipidoids and uses thereof
WO2014027006A1 (en) 2012-08-13 2014-02-20 Edko Pazarlama Tanitim Ticaret Limited Sirketi Bioadhesive formulations for use in drug delivery
US9512456B2 (en) 2012-08-14 2016-12-06 Modernatx, Inc. Enzymes and polymerases for the synthesis of RNA
CA2881605A1 (en) 2012-08-14 2014-02-20 Aaron FROESE Internal structured self assembling liposomes
WO2014028209A1 (en) 2012-08-14 2014-02-20 The Trustees Of The University Of Pennsylvania Stabilizing shear-thinning hydrogels
WO2014028763A1 (en) 2012-08-15 2014-02-20 The University Of Chicago Exosome-based therapeutics against neurodegenerative disorders
WO2014039185A1 (en) 2012-09-05 2014-03-13 Creighton University Polymeric nanoparticles in a thermosensitive gel for coital-independent vaginal prophylaxis of hiv
US8703197B2 (en) 2012-09-13 2014-04-22 International Business Machines Corporation Branched polyamines for delivery of biologically active materials
EP2895146A1 (en) 2012-09-17 2015-07-22 BIND Therapeutics, Inc. Therapeutic nanoparticles comprising a therapeutic agent and methods of making and using same
JP6356678B2 (ja) 2012-09-17 2018-07-11 ファイザー・インク 治療用ナノ粒子を製造する方法
WO2014047649A1 (en) 2012-09-24 2014-03-27 The Regents Of The University Of California Methods for arranging and packing nucleic acids for unusual resistance to nucleases and targeted delivery for gene therapy
CA2925687A1 (en) 2012-09-27 2014-04-03 The University Of North Carolina At Chapel Hill Lipid coated nanoparticles containing agents having low aqueous and lipid solubilities and methods thereof
WO2014093924A1 (en) 2012-12-13 2014-06-19 Moderna Therapeutics, Inc. Modified nucleic acid molecules and uses thereof
US20140100178A1 (en) 2012-10-04 2014-04-10 Aslam Ansari Composition and methods for site-specific drug delivery to treat malaria and other liver diseases
WO2014053879A1 (en) 2012-10-04 2014-04-10 Centre National De La Recherche Scientifique Cell penetrating peptides for intracellular delivery of molecules
WO2014053882A1 (en) 2012-10-04 2014-04-10 Centre National De La Recherche Scientifique Cell penetrating peptides for intracellular delivery of molecules
WO2014053881A1 (en) 2012-10-04 2014-04-10 Centre National De La Recherche Scientifique Cell penetrating peptides for intracellular delivery of molecules
EP2716655A1 (en) 2012-10-04 2014-04-09 Institut Pasteur Neutralizing antibodies directed against Hepatitis C virus ectodomain glycoprotein E2
US20150202153A1 (en) 2012-10-04 2015-07-23 University Of The Witwatersrand, Johannesburg Liposomal drug delivery system
WO2014053880A1 (en) 2012-10-04 2014-04-10 Centre National De La Recherche Scientifique Cell penetrating peptides for intracellular delivery of molecules
EP2716689A1 (en) 2012-10-05 2014-04-09 National University of Ireland, Galway Polymer comprising a plurality of branches having at least one disulfide group and/or at least one vinyl group
WO2014064534A2 (en) 2012-10-05 2014-05-01 Chrontech Pharma Ab Injection needle, device, immunogenic compositions and method of use
US9931410B2 (en) 2012-10-09 2018-04-03 The Brigham And Women's Hospital, Inc. Nanoparticles for targeted delivery of multiple therapeutic agents and methods of use
US20140106260A1 (en) 2012-10-11 2014-04-17 The Trustees Of The University Of Pennsylvania Core-shell nanoparticulate compositions and methods
US9662402B2 (en) 2012-10-16 2017-05-30 Endocyte, Inc. Drug delivery conjugates containing unnatural amino acids and methods for using
CN118955699A (zh) 2012-10-18 2024-11-15 洛克菲勒大学 广泛中和性抗hiv抗体
CN104918639B (zh) 2012-10-22 2018-01-26 萨拜格Rfa公司 用于将治疗剂递送到活细胞和细胞核中的系统
WO2014066912A1 (en) 2012-10-26 2014-05-01 Vanderbilt University Polymeric nanoparticles
WO2014066898A1 (en) 2012-10-26 2014-05-01 The Johns Hopkins University A layer-by-layer approach to co-deliver dna and sirna via aunps: a potential platform for modifying release kinetics
AU2013336582A1 (en) 2012-10-26 2015-06-11 Nlife Therapeutics, S.L. Compositions and methods for selective delivery of oligonucleotide molecules to cell types
WO2014067551A1 (en) 2012-10-29 2014-05-08 Technische Universität Dortmund T7 rna polymerase variants and methods of using the same
EP2752740A4 (en) * 2012-10-31 2015-03-11 Huawei Device Co Ltd DRAWING CONTROL METHOD, DEVICE THEREFOR AND MOBILE DEVICE
KR102315098B1 (ko) 2012-11-01 2021-10-21 팩터 바이오사이언스 인크. 세포에서 단백질을 발현시키는 방법들과 생성물들
US9444624B2 (en) 2012-11-02 2016-09-13 Facebook, Inc. Providing user authentication
WO2014071072A2 (en) 2012-11-02 2014-05-08 Pungente Michael D Novel cationic carotenoid-based lipids for cellular nucleic acid uptake
US10017767B2 (en) 2012-11-05 2018-07-10 Fondazione Centro San Raffaele Targets in multiple myeloma and other disorders
WO2014074289A1 (en) 2012-11-06 2014-05-15 Rochal Industries, Llp Delivery of biologically-active agents using volatile, hydrophobic solvents
WO2014074597A1 (en) 2012-11-06 2014-05-15 President And Fellows Of Harvard College Compositions and methods relating to complex nucleic acid nanostructures
WO2014072999A1 (en) 2012-11-07 2014-05-15 Council Of Scientific And Industrial Research Nanocomplex containing cationic peptide for biomolecule delivery
EP2916873B1 (en) 2012-11-07 2017-07-26 Council of Scientific & Industrial Research Nanocomplex containing amphipathic peptide useful for efficient transfection of biomolecules
KR102149206B1 (ko) 2012-11-08 2020-08-31 세센 바이오, 아이엔씨. 인터루킨-6의 길항제 및 이의 용도
TW201920677A (zh) 2012-11-08 2019-06-01 美商武田疫苗股份有限公司 登革熱病毒血清型４型之建構物的組成物、方法及用途
CN105452290A (zh) 2012-11-08 2016-03-30 诺维信生物制药丹麦公司 白蛋白变体
ES3023054T3 (en) 2012-11-08 2025-05-29 Clearside Biomedical Inc Methods for the treatment of ocular disease in human subjects
US9200119B2 (en) 2012-11-09 2015-12-01 Momentive Performance Materials Inc. Silicon-containing zwitterionic linear copolymer composition
AU2013343864B2 (en) 2012-11-09 2019-04-04 BioNTech SE Method for cellular RNA expression
WO2014072468A1 (en) 2012-11-09 2014-05-15 Velin-Pharma A/S Compositions for pulmonary delivery
WO2014071963A1 (en) 2012-11-09 2014-05-15 Biontech Ag Method for cellular rna expression
EP2916862B1 (en) 2012-11-12 2020-01-08 GenVec, Inc. Malaria antigens and methods of use
EP2916835A4 (en) 2012-11-12 2016-07-27 Redwood Bioscience Inc COMPOUNDS AND METHOD FOR PRODUCING A CONJUGATE
GB201220354D0 (en) 2012-11-12 2012-12-26 Medpharm Ltd Dermal compositions
WO2014078399A1 (en) 2012-11-13 2014-05-22 Baylor College Of Medicine Multi-arm biodegradable polymers for nucleic acid delivery
WO2014078636A1 (en) 2012-11-16 2014-05-22 President And Fellows Of Harvard College Nucleic acid hydrogel self-assembly
US9310374B2 (en) 2012-11-16 2016-04-12 Redwood Bioscience, Inc. Hydrazinyl-indole compounds and methods for producing a conjugate
EP2732825B1 (en) 2012-11-19 2015-07-01 Invivogen Conjugates of a TLR7 and/or TLR8 agonist and a TLR2 agonist
CN104853747B (zh) 2012-11-19 2020-06-19 理工研究与开发基金公司 用于体内递送的脂质体
US20140141037A1 (en) 2012-11-20 2014-05-22 Novartis Ag Rsv f prefusion trimers
WO2014081849A1 (en) 2012-11-20 2014-05-30 Phasebio Pharmaceuticals, Inc. Formulations of active agents for sustained release
WO2014081299A1 (en) 2012-11-22 2014-05-30 Tagworks Pharmaceuticals B.V. Activatable liposomes
WO2014081300A1 (en) 2012-11-22 2014-05-30 Tagworks Pharmaceuticals B.V. Channel protein activatable liposomes
FI2922574T3 (fi) 2012-11-22 2023-08-11 Tagworks Pharmaceuticals B V Kemiallisesti pilkkoutuva ryhmä
SMT202200337T1 (it) 2012-11-26 2022-09-14 Modernatx Inc Rna modificato al livello del terminale
WO2014093574A1 (en) 2012-12-13 2014-06-19 Moderna Therapeutics, Inc. Modified polynucleotides for altering cell phenotype
HK1214962A1 (zh) 2013-01-10 2016-08-12 Seqirus UK Limited 流感病毒免疫原性组合物及其应用
AU2013374345A1 (en) 2013-01-17 2015-08-06 Moderna Therapeutics, Inc. Signal-sensor polynucleotides for the alteration of cellular phenotypes
HK1220122A1 (zh) 2013-03-09 2017-04-28 Modernatx, Inc. Mrna的异源未转录区域
WO2014158795A1 (en) 2013-03-12 2014-10-02 Moderna Therapeutics, Inc. Diagnosis and treatment of fibrosis
EP2968391A1 (en) 2013-03-13 2016-01-20 Moderna Therapeutics, Inc. Long-lived polynucleotide molecules
EP2971010B1 (en) 2013-03-14 2020-06-10 ModernaTX, Inc. Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions
EP2970351B1 (en) 2013-03-14 2017-09-13 Translate Bio, Inc. Ribonucleic acids with 4'-thio-modified nucleotides and related methods
US10077439B2 (en) 2013-03-15 2018-09-18 Modernatx, Inc. Removal of DNA fragments in mRNA production process
WO2014144767A1 (en) 2013-03-15 2014-09-18 Moderna Therapeutics, Inc. Ion exchange purification of mrna
WO2014144039A1 (en) 2013-03-15 2014-09-18 Moderna Therapeutics, Inc. Characterization of mrna molecules
WO2014144711A1 (en) 2013-03-15 2014-09-18 Moderna Therapeutics, Inc. Analysis of mrna heterogeneity and stability
WO2014152031A1 (en) 2013-03-15 2014-09-25 Moderna Therapeutics, Inc. Ribonucleic acid purification
WO2014152027A1 (en) 2013-03-15 2014-09-25 Moderna Therapeutics, Inc. Manufacturing methods for production of rna transcripts
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
HUE056760T2 (hu) 2013-07-11 2022-03-28 Modernatx Inc A CRISPR-hez kapcsolódó fehérjéket és a szintetikus SGRNS-ket kódoló szintetikus polinukleotidokat tartalmazó készítmények és felhasználási módjaik
EP3041938A1 (en) 2013-09-03 2016-07-13 Moderna Therapeutics, Inc. Circular polynucleotides
AU2014315287A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Chimeric polynucleotides
EP3043826A4 (en) 2013-09-13 2017-05-24 Moderna Therapeutics, Inc. Polynucleotide compositions containing amino acids
US10023626B2 (en) 2013-09-30 2018-07-17 Modernatx, Inc. Polynucleotides encoding immune modulating polypeptides
EP3052511A4 (en) 2013-10-02 2017-05-31 Moderna Therapeutics, Inc. Polynucleotide molecules and uses thereof
US20160264614A1 (en) 2013-10-02 2016-09-15 Moderna Therapeutics, Inc. Polynucleotide molecules and uses thereof
US10323076B2 (en) 2013-10-03 2019-06-18 Modernatx, Inc. Polynucleotides encoding low density lipoprotein receptor
WO2015058069A1 (en) 2013-10-18 2015-04-23 Moderna Therapeutics, Inc. Compositions and methods for tolerizing cellular systems
US20170173128A1 (en) 2013-12-06 2017-06-22 Moderna TX, Inc. Targeted adaptive vaccines
EP2918275B1 (en) 2013-12-13 2016-05-18 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
WO2015105926A1 (en) 2014-01-08 2015-07-16 Moderna Therapeutics, Inc. Polynucleotides for the in vivo production of antibodies
SG10201912038TA (en) 2014-04-23 2020-02-27 Modernatx Inc Nucleic acid vaccines
US20170136132A1 (en) 2014-06-19 2017-05-18 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
WO2015196128A2 (en) 2014-06-19 2015-12-23 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
US20170175129A1 (en) 2014-06-19 2017-06-22 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
WO2016011226A1 (en) 2014-07-16 2016-01-21 Moderna Therapeutics, Inc. Chimeric polynucleotides
WO2016011222A2 (en) 2014-07-16 2016-01-21 Moderna Therapeutics, Inc. Circular polynucleotides
EP3188749A4 (en) 2014-09-03 2018-06-13 Moderna Therapeutics, Inc. Tolerogenic compositions and methods
WO2016118724A1 (en) 2015-01-21 2016-07-28 Moderna Therapeutics, Inc. Lipid nanoparticle compositions
WO2016118725A1 (en) 2015-01-23 2016-07-28 Moderna Therapeutics, Inc. Lipid nanoparticle compositions
RU2727592C2 (ru) 2015-11-12 2020-07-22 Конинклейке Филипс Н.В. Конструкция накладки на грудь для молокоотсоса, молокоотсос и способ работы
US10870110B2 (en) 2015-12-11 2020-12-22 Babson Diagnostics, Inc. Specimen container and centrifugation method for separating serum or plasma from whole blood therewith
US10563897B2 (en) 2018-02-13 2020-02-18 Carrier Corporation Transport refrigeration unit with a renewable energy source and method of operation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE202007018832U1 (de) 2006-04-19 2009-09-17 Arcelormittal France Geschweißtes Teil mit sehr hohen mechanischen Eigenschaften aus einem gewalzten und beschichteten Blech
EP2942143A1 (en) 2014-05-09 2015-11-11 Gestamp HardTech AB Methods for joining two blanks and blanks and products obtained
US20170253941A1 (en) 2014-07-30 2017-09-07 Arcelormittal Method for Fabricating Steel Sheet for Press Hardening, and Parts Obtained by this Method
EP3222745A1 (en) 2014-11-19 2017-09-27 Nippon Steel & Sumitomo Metal Corporation Laser welded joint, automotive part, method for producing laser welded joint, and method for manufacturing automotive part

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
REGINA J. R., J. N. DUPONT, AND A. R. MARDER: "The Effect of Chromium on the Weldability and Microstructure of Fe-Cr-AI Weld Cladding", WELDING RESEARCH, vol. 86, 1 June 2017 (2017-06-01), pages 170 - 178, XP093062437

Cited By (384)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10414824B2 (en) 2002-11-22 2019-09-17 Ganymed Pharmaceuticals Ag Genetic products differentially expressed in tumors and the use thereof
US11298426B2 (en) 2003-10-14 2022-04-12 BioNTech SE Recombinant vaccines and use thereof
US9775785B2 (en) 2004-05-18 2017-10-03 Ganymed Pharmaceuticals Ag Antibody to genetic products differentially expressed in tumors and the use thereof
US10106800B2 (en) 2005-09-28 2018-10-23 Biontech Ag Modification of RNA, producing an increased transcript stability and translation efficiency
US12385049B2 (en) 2005-09-28 2025-08-12 BioNTech SE Modification of RNA, producing an increased transcript stability and translation efficiency
US9499609B2 (en) 2005-11-24 2016-11-22 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US10017564B2 (en) 2005-11-24 2018-07-10 Ganymed Pharmaceuticals Gmbh Monoclonal antibodies against claudin-18 for treatment of cancer
US11739139B2 (en) 2005-11-24 2023-08-29 Astellas Pharma Inc. Monoclonal antibodies against Claudin-18 for treatment of cancer
US10738108B2 (en) 2005-11-24 2020-08-11 Astellas Pharma Inc. Monoclonal antibodies against claudin-18 for treatment of cancer
US10174104B2 (en) 2005-11-24 2019-01-08 Ganymed Pharmaceuticals Gmbh Monoclonal antibodies against claudin-18 for treatment of cancer
US9751934B2 (en) 2005-11-24 2017-09-05 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US9212228B2 (en) 2005-11-24 2015-12-15 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US10576166B2 (en) 2009-12-01 2020-03-03 Translate Bio, Inc. Liver specific delivery of messenger RNA
US11730754B2 (en) 2010-07-06 2023-08-22 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11857562B2 (en) 2010-07-06 2024-01-02 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11596645B2 (en) 2010-07-06 2023-03-07 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11638693B2 (en) 2010-07-06 2023-05-02 Glaxosmithkline Biologicals Sa Vaccine for eliciting immune response comprising RNA encoding an immunogen and lipid formulations comprising mole percentage of lipids
US11638694B2 (en) 2010-07-06 2023-05-02 Glaxosmithkline Biologicals Sa Vaccine for eliciting immune response comprising lipid formulations and RNA encoding multiple immunogens
US20220125723A1 (en) 2010-07-06 2022-04-28 Glaxosmithkline Biologicals Sa Lipid formulations with viral immunogens
US11891608B2 (en) 2010-07-06 2024-02-06 Glaxosmithkline Biologicals Sa Immunization of large mammals with low doses of RNA
US11865080B2 (en) 2010-07-06 2024-01-09 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11655475B2 (en) 2010-07-06 2023-05-23 Glaxosmithkline Biologicals Sa Immunisation of large mammals with low doses of RNA
US11666534B2 (en) 2010-07-06 2023-06-06 Glaxosmithkline Biologicals Sa Methods of administering lipid formulations with viral immunogens
US11690862B1 (en) 2010-07-06 2023-07-04 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11690865B2 (en) 2010-07-06 2023-07-04 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11690861B2 (en) 2010-07-06 2023-07-04 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11690863B2 (en) 2010-07-06 2023-07-04 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11690864B2 (en) 2010-07-06 2023-07-04 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11696923B2 (en) 2010-07-06 2023-07-11 Glaxosmithkline Biologicals, Sa Delivery of RNA to trigger multiple immune pathways
US11707482B2 (en) 2010-07-06 2023-07-25 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11839686B2 (en) 2010-07-06 2023-12-12 Glaxosmithkline Biologicals Sa Lipid formulations with viral immunogens
US11717529B2 (en) 2010-07-06 2023-08-08 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11905514B2 (en) 2010-07-06 2024-02-20 Glaxosmithkline Biological Sa Immunisation of large mammals with low doses of RNA
US11883534B2 (en) 2010-07-06 2024-01-30 Glaxosmithkline Biologicals Sa Immunisation with lipid formulations with RNA encoding immunogens
US11739334B2 (en) 2010-07-06 2023-08-29 Glaxosmithkline Biologicals Sa Immunisation of large mammals with low doses of RNA
US11845925B2 (en) 2010-07-06 2023-12-19 Glaxosmithkline Biologicals Sa Immunisation of large mammals with low doses of RNA
US11913001B2 (en) 2010-07-06 2024-02-27 Glaxosmithkline Biologicals Sa Immunisation of large mammals with low doses of RNA
US11857681B2 (en) 2010-07-06 2024-01-02 Glaxosmithkline Biologicals Sa Lipid formulations with RNA encoding immunogens
US11759475B2 (en) 2010-07-06 2023-09-19 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US12186333B2 (en) 2010-07-06 2025-01-07 Glaxosmithkline Biologicals Sa Delivery of RNA to trigger multiple immune pathways
US11766401B2 (en) 2010-07-06 2023-09-26 Glaxosmithkline Biologicals Sa Methods of administering lipid formulations with immunogens
US11786467B2 (en) 2010-07-06 2023-10-17 Glaxosmithkline Biologicals Sa Lipid formulations with immunogens
US11851660B2 (en) 2010-07-06 2023-12-26 Glaxosmithkline Biologicals Sa Immunisation of large mammals with low doses of RNA
US11773395B1 (en) 2010-07-06 2023-10-03 Glaxosmithkline Biologicals Sa Immunization of large mammals with low doses of RNA
US11850305B2 (en) 2010-07-06 2023-12-26 Glaxosmithkline Biologicals Sa Method of making lipid formulations with RNA encoding immunogens
US9937233B2 (en) 2010-08-06 2018-04-10 Modernatx, Inc. Engineered nucleic acids and methods of use thereof
US9181319B2 (en) 2010-08-06 2015-11-10 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US9447164B2 (en) 2010-08-06 2016-09-20 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US8822663B2 (en) 2010-08-06 2014-09-02 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US11759422B2 (en) 2010-08-31 2023-09-19 Glaxosmithkline Biologicals Sa Pegylated liposomes for delivery of immunogen-encoding RNA
US10350265B2 (en) 2010-09-22 2019-07-16 The Regents Of The University Of Colorado, A Body Corporate Therapeutic applications of Smad7
US9334328B2 (en) 2010-10-01 2016-05-10 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9657295B2 (en) 2010-10-01 2017-05-23 Modernatx, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9701965B2 (en) 2010-10-01 2017-07-11 Modernatx, Inc. Engineered nucleic acids and methods of use thereof
US10064959B2 (en) 2010-10-01 2018-09-04 Modernatx, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US11639370B2 (en) 2010-10-11 2023-05-02 Glaxosmithkline Biologicals Sa Antigen delivery platforms
US9956271B2 (en) 2010-11-30 2018-05-01 Translate Bio, Inc. mRNA for use in treatment of human genetic diseases
US11135274B2 (en) 2010-11-30 2021-10-05 Translate Bio, Inc. MRNA for use in treatment of human genetic diseases
US9533047B2 (en) 2011-03-31 2017-01-03 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US12364763B2 (en) 2011-03-31 2025-07-22 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US11911474B2 (en) 2011-03-31 2024-02-27 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US10898574B2 (en) 2011-03-31 2021-01-26 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US12409226B2 (en) 2011-03-31 2025-09-09 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US12419957B2 (en) 2011-03-31 2025-09-23 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US9950068B2 (en) 2011-03-31 2018-04-24 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US10738355B2 (en) 2011-05-24 2020-08-11 Tron-Translationale Onkologie An Der Universitätsmedizin Der Johannes Gutenberg-Universität Mainz Ggmbh Individualized vaccines for cancer
US11248264B2 (en) 2011-05-24 2022-02-15 Tron-Translationale Onkologie An Der Universitätsmedizin Der Johannes Gutenberg-Universität Mainz Ggmbh Individualized vaccines for cancer
US10413618B2 (en) 2011-06-08 2019-09-17 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11547764B2 (en) 2011-06-08 2023-01-10 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery
US10888626B2 (en) 2011-06-08 2021-01-12 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11052159B2 (en) 2011-06-08 2021-07-06 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11185595B2 (en) 2011-06-08 2021-11-30 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11730825B2 (en) 2011-06-08 2023-08-22 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US9308281B2 (en) 2011-06-08 2016-04-12 Shire Human Genetic Therapies, Inc. MRNA therapy for Fabry disease
US11951180B2 (en) 2011-06-08 2024-04-09 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery
US11951181B2 (en) 2011-06-08 2024-04-09 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US10238754B2 (en) 2011-06-08 2019-03-26 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery
US11951179B2 (en) 2011-06-08 2024-04-09 Translate Bio, Inc. Lipid nanoparticle compositions and methods for MRNA delivery
US9597413B2 (en) 2011-06-08 2017-03-21 Shire Human Genetic Therapies, Inc. Pulmonary delivery of mRNA
US11291734B2 (en) 2011-06-08 2022-04-05 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11338044B2 (en) 2011-06-08 2022-05-24 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US10507249B2 (en) 2011-06-08 2019-12-17 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US10350303B1 (en) 2011-06-08 2019-07-16 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US12121592B2 (en) 2011-06-08 2024-10-22 Translate Bio, Inc. Lipid nanoparticle compositions and methods for mRNA delivery
US11896636B2 (en) 2011-07-06 2024-02-13 Glaxosmithkline Biologicals Sa Immunogenic combination compositions and uses thereof
US10022425B2 (en) 2011-09-12 2018-07-17 Modernatx, Inc. Engineered nucleic acids and methods of use thereof
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US10751386B2 (en) 2011-09-12 2020-08-25 Modernatx, Inc. Engineered nucleic acids and methods of use thereof
EP3682905B1 (en) 2011-10-03 2021-12-01 ModernaTX, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9428535B2 (en) 2011-10-03 2016-08-30 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9186372B2 (en) 2011-12-16 2015-11-17 Moderna Therapeutics, Inc. Split dose administration
EP2791160B1 (en) 2011-12-16 2022-03-02 ModernaTX, Inc. Modified mrna compositions
US9271996B2 (en) 2011-12-16 2016-03-01 Moderna Therapeutics, Inc. Formulation and delivery of PLGA microspheres
US9295689B2 (en) 2011-12-16 2016-03-29 Moderna Therapeutics, Inc. Formulation and delivery of PLGA microspheres
US11559587B2 (en) 2012-03-26 2023-01-24 Tron-Translationale Onkologie An Der Universitätsmedizin Der Johannes Gutenberg-Universität Mainz Ggmbh RNA formulation for immunotherapy
US10485884B2 (en) 2012-03-26 2019-11-26 Biontech Rna Pharmaceuticals Gmbh RNA formulation for immunotherapy
US9114113B2 (en) 2012-04-02 2015-08-25 Moderna Therapeutics, Inc. Modified polynucleotides encoding citeD4
US10463751B2 (en) 2012-04-02 2019-11-05 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9827332B2 (en) 2012-04-02 2017-11-28 Modernatx, Inc. Modified polynucleotides for the production of proteins
US9814760B2 (en) 2012-04-02 2017-11-14 Modernatx, Inc. Modified polynucleotides for the production of biologics and proteins associated with human disease
US8999380B2 (en) 2012-04-02 2015-04-07 Moderna Therapeutics, Inc. Modified polynucleotides for the production of biologics and proteins associated with human disease
US10772975B2 (en) 2012-04-02 2020-09-15 Modernatx, Inc. Modified Polynucleotides for the production of biologics and proteins associated with human disease
US9301993B2 (en) 2012-04-02 2016-04-05 Moderna Therapeutics, Inc. Modified polynucleotides encoding apoptosis inducing factor 1
US9303079B2 (en) 2012-04-02 2016-04-05 Moderna Therapeutics, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9782462B2 (en) 2012-04-02 2017-10-10 Modernatx, Inc. Modified polynucleotides for the production of proteins associated with human disease
US9878056B2 (en) 2012-04-02 2018-01-30 Modernatx, Inc. Modified polynucleotides for the production of cosmetic proteins and peptides
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US9050297B2 (en) 2012-04-02 2015-06-09 Moderna Therapeutics, Inc. Modified polynucleotides encoding aryl hydrocarbon receptor nuclear translocator
US9061059B2 (en) 2012-04-02 2015-06-23 Moderna Therapeutics, Inc. Modified polynucleotides for treating protein deficiency
US10703789B2 (en) 2012-04-02 2020-07-07 Modernatx, Inc. Modified polynucleotides for the production of secreted proteins
US9089604B2 (en) 2012-04-02 2015-07-28 Moderna Therapeutics, Inc. Modified polynucleotides for treating galactosylceramidase protein deficiency
US9587003B2 (en) 2012-04-02 2017-03-07 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
US9254311B2 (en) 2012-04-02 2016-02-09 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins
US9255129B2 (en) 2012-04-02 2016-02-09 Moderna Therapeutics, Inc. Modified polynucleotides encoding SIAH E3 ubiquitin protein ligase 1
US9233141B2 (en) 2012-04-02 2016-01-12 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins associated with blood and lymphatic disorders
US9095552B2 (en) 2012-04-02 2015-08-04 Moderna Therapeutics, Inc. Modified polynucleotides encoding copper metabolism (MURR1) domain containing 1
US9220755B2 (en) 2012-04-02 2015-12-29 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins associated with blood and lymphatic disorders
US9221891B2 (en) 2012-04-02 2015-12-29 Moderna Therapeutics, Inc. In vivo production of proteins
US10583203B2 (en) 2012-04-02 2020-03-10 Modernatx, Inc. In vivo production of proteins
US9220792B2 (en) 2012-04-02 2015-12-29 Moderna Therapeutics, Inc. Modified polynucleotides encoding aquaporin-5
US9216205B2 (en) 2012-04-02 2015-12-22 Moderna Therapeutics, Inc. Modified polynucleotides encoding granulysin
US10385106B2 (en) 2012-04-02 2019-08-20 Modernatx, Inc. Modified polynucleotides for the production of secreted proteins
US9192651B2 (en) 2012-04-02 2015-11-24 Moderna Therapeutics, Inc. Modified polynucleotides for the production of secreted proteins
US9107886B2 (en) 2012-04-02 2015-08-18 Moderna Therapeutics, Inc. Modified polynucleotides encoding basic helix-loop-helix family member E41
US10577403B2 (en) 2012-04-02 2020-03-03 Modernatx, Inc. Modified polynucleotides for the production of secreted proteins
US9828416B2 (en) 2012-04-02 2017-11-28 Modernatx, Inc. Modified polynucleotides for the production of secreted proteins
US10501512B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides
US10501513B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
US9149506B2 (en) 2012-04-02 2015-10-06 Moderna Therapeutics, Inc. Modified polynucleotides encoding septin-4
US11564998B2 (en) 2012-04-02 2023-01-31 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9675668B2 (en) 2012-04-02 2017-06-13 Moderna Therapeutics, Inc. Modified polynucleotides encoding hepatitis A virus cellular receptor 2
US10493167B2 (en) 2012-04-02 2019-12-03 Modernatx, Inc. In vivo production of proteins
US11976130B2 (en) 2012-05-09 2024-05-07 Astellas Pharma Inc. Antibodies against claudin 18.2 useful in cancer diagnosis
US9512232B2 (en) 2012-05-09 2016-12-06 Ganymed Pharmaceuticals Ag Antibodies against Claudin 18.2 useful in cancer diagnosis
US10053512B2 (en) 2012-05-09 2018-08-21 Ganymed Pharmaceuticals Ag Antibodies against claudin 18.2 useful in cancer diagnosis
US10245229B2 (en) 2012-06-08 2019-04-02 Translate Bio, Inc. Pulmonary delivery of mRNA to non-lung target cells
US11254936B2 (en) 2012-06-08 2022-02-22 Translate Bio, Inc. Nuclease resistant polynucleotides and uses thereof
US11090264B2 (en) 2012-06-08 2021-08-17 Translate Bio, Inc. Pulmonary delivery of mRNA to non-lung target cells
US9512456B2 (en) 2012-08-14 2016-12-06 Modernatx, Inc. Enzymes and polymerases for the synthesis of RNA
US10758592B2 (en) 2012-10-09 2020-09-01 Sanofi Exendin-4 derivatives as dual GLP1/glucagon agonists
US10925935B2 (en) 2012-11-26 2021-02-23 Modernatx, Inc. Terminally Modified RNA
US12023371B2 (en) 2012-11-26 2024-07-02 Modernatx, Inc. Terminally modified RNA
US9597380B2 (en) 2012-11-26 2017-03-21 Modernatx, Inc. Terminally modified RNA
US11504419B2 (en) 2012-11-28 2022-11-22 BioNTech SE Individualized vaccines for cancer
US10155031B2 (en) 2012-11-28 2018-12-18 Biontech Rna Pharmaceuticals Gmbh Individualized vaccines for cancer
US9745360B2 (en) 2012-12-21 2017-08-29 Sanofi Dual GLP1/GIP or trigonal GLP1/GIP/glucagon agonists
US9670261B2 (en) 2012-12-21 2017-06-06 Sanofi Functionalized exendin-4 derivatives
US10253079B2 (en) 2012-12-21 2019-04-09 Sanofi Functionalized Exendin-4 derivatives
US11708396B2 (en) 2013-01-17 2023-07-25 Modernatx, Inc. Signal-sensor polynucleotides for the alteration of cellular phenotypes
EP3434774A1 (en) * 2013-01-17 2019-01-30 ModernaTX, Inc. Signal-sensor polynucleotides for the alteration of cellular phenotypes
WO2014113089A3 (en) * 2013-01-17 2014-09-12 Moderna Therapeutics, Inc. Signal-sensor polynucleotides for the alteration of cellular phenotypes
US10456448B2 (en) 2013-03-08 2019-10-29 The Regents Of The University Of Colorado, A Body Corporate PTD-SMAD7 therapeutics
EP2964774A4 (en) * 2013-03-08 2016-08-10 Univ Colorado Regents PTD SMAD7 THERAPEUTICS
US11603399B2 (en) 2013-03-13 2023-03-14 Modernatx, Inc. Long-lived polynucleotide molecules
US10584165B2 (en) 2013-03-14 2020-03-10 Translate Bio, Inc. Methods and compositions for delivering mRNA coded antibodies
US10876104B2 (en) 2013-03-14 2020-12-29 Translate Bio, Inc. Methods for purification of messenger RNA
US11820977B2 (en) 2013-03-14 2023-11-21 Translate Bio, Inc. Methods for purification of messenger RNA
US9181321B2 (en) 2013-03-14 2015-11-10 Shire Human Genetic Therapies, Inc. CFTR mRNA compositions and related methods and uses
US10087247B2 (en) 2013-03-14 2018-10-02 Translate Bio, Inc. Methods and compositions for delivering mRNA coded antibodies
US12234446B2 (en) 2013-03-14 2025-02-25 Translate Bio, Inc. Methods for purification of messenger RNA
US9957499B2 (en) 2013-03-14 2018-05-01 Translate Bio, Inc. Methods for purification of messenger RNA
US11692189B2 (en) 2013-03-14 2023-07-04 Translate Bio, Inc. Methods for purification of messenger RNA
US10420791B2 (en) 2013-03-14 2019-09-24 Translate Bio, Inc. CFTR MRNA compositions and related methods and uses
US11510937B2 (en) 2013-03-14 2022-11-29 Translate Bio, Inc. CFTR MRNA compositions and related methods and uses
US10899830B2 (en) 2013-03-14 2021-01-26 Translate Bio, Inc. Methods and compositions for delivering MRNA coded antibodies
US10258698B2 (en) 2013-03-14 2019-04-16 Modernatx, Inc. Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions
US9713626B2 (en) 2013-03-14 2017-07-25 Rana Therapeutics, Inc. CFTR mRNA compositions and related methods and uses
US11845772B2 (en) 2013-03-15 2023-12-19 Modernatx, Inc. Ribonucleic acid purification
US10646504B2 (en) 2013-03-15 2020-05-12 Translate Bio, Inc. Synergistic enhancement of the delivery of nucleic acids via blended formulations
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
US10858647B2 (en) 2013-03-15 2020-12-08 Modernatx, Inc. Removal of DNA fragments in mRNA production process
US10138507B2 (en) 2013-03-15 2018-11-27 Modernatx, Inc. Manufacturing methods for production of RNA transcripts
US10590161B2 (en) 2013-03-15 2020-03-17 Modernatx, Inc. Ion exchange purification of mRNA
US12453739B2 (en) 2013-03-15 2025-10-28 Translate Bio, Inc. Synergistic enhancement of the delivery of nucleic acids via blended formulations
US10077439B2 (en) 2013-03-15 2018-09-18 Modernatx, Inc. Removal of DNA fragments in mRNA production process
US11377470B2 (en) 2013-03-15 2022-07-05 Modernatx, Inc. Ribonucleic acid purification
US10130649B2 (en) 2013-03-15 2018-11-20 Translate Bio, Inc. Synergistic enhancement of the delivery of nucleic acids via blended formulations
US11222711B2 (en) 2013-05-10 2022-01-11 BioNTech SE Predicting immunogenicity of T cell epitopes
US11027025B2 (en) 2013-07-11 2021-06-08 Modernatx, Inc. Compositions comprising synthetic polynucleotides encoding CRISPR related proteins and synthetic sgRNAs and methods of use
WO2015034925A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Circular polynucleotides
WO2015034928A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Chimeric polynucleotides
EP3052106A4 (en) * 2013-09-30 2017-07-19 ModernaTX, Inc. Polynucleotides encoding immune modulating polypeptides
US10815291B2 (en) 2013-09-30 2020-10-27 Modernatx, Inc. Polynucleotides encoding immune modulating polypeptides
US10023626B2 (en) 2013-09-30 2018-07-17 Modernatx, Inc. Polynucleotides encoding immune modulating polypeptides
US10385088B2 (en) 2013-10-02 2019-08-20 Modernatx, Inc. Polynucleotide molecules and uses thereof
US10323076B2 (en) 2013-10-03 2019-06-18 Modernatx, Inc. Polynucleotides encoding low density lipoprotein receptor
WO2015051214A1 (en) 2013-10-03 2015-04-09 Moderna Therapeutics, Inc. Polynucleotides encoding low density lipoprotein receptor
US9629804B2 (en) 2013-10-22 2017-04-25 Shire Human Genetic Therapies, Inc. Lipid formulations for delivery of messenger RNA
US11224642B2 (en) 2013-10-22 2022-01-18 Translate Bio, Inc. MRNA therapy for argininosuccinate synthetase deficiency
US10780052B2 (en) 2013-10-22 2020-09-22 Translate Bio, Inc. CNS delivery of MRNA and uses thereof
US10208295B2 (en) 2013-10-22 2019-02-19 Translate Bio, Inc. MRNA therapy for phenylketonuria
US11377642B2 (en) 2013-10-22 2022-07-05 Translate Bio, Inc. mRNA therapy for phenylketonuria
US10493031B2 (en) 2013-10-22 2019-12-03 Translate Bio, Inc. Lipid formulations for delivery of messenger RNA
US10052284B2 (en) 2013-10-22 2018-08-21 Translate Bio, Inc. Lipid formulations for delivery of messenger RNA
US9522176B2 (en) 2013-10-22 2016-12-20 Shire Human Genetic Therapies, Inc. MRNA therapy for phenylketonuria
US12016954B2 (en) 2013-10-22 2024-06-25 Translate Bio, Inc. CNS delivery of mRNA and uses thereof
US10959953B2 (en) 2013-10-22 2021-03-30 Translate Bio, Inc. Lipid formulations for delivery of messenger RNA
US11890377B2 (en) 2013-10-22 2024-02-06 Translate Bio, Inc. Lipid formulations for delivery of messenger RNA
US9751926B2 (en) 2013-12-13 2017-09-05 Sanofi Dual GLP-1/GIP receptor agonists
US9750788B2 (en) 2013-12-13 2017-09-05 Sanofi Non-acylated exendin-4 peptide analogues
US9694053B2 (en) 2013-12-13 2017-07-04 Sanofi Dual GLP-1/glucagon receptor agonists
US9789165B2 (en) 2013-12-13 2017-10-17 Sanofi Exendin-4 peptide analogues as dual GLP-1/GIP receptor agonists
EP3122878B1 (en) 2014-03-24 2018-10-24 Translate Bio, Inc. Mrna therapy for the treatment of ocular diseases
EP3699274A1 (en) * 2014-03-24 2020-08-26 Translate Bio, Inc. Mrna therapy for the treatment of ocular diseases
US9758561B2 (en) 2014-04-07 2017-09-12 Sanofi Dual GLP-1/glucagon receptor agonists derived from exendin-4
US9771406B2 (en) 2014-04-07 2017-09-26 Sanofi Peptidic dual GLP-1/glucagon receptor agonists derived from exendin-4
US9775904B2 (en) 2014-04-07 2017-10-03 Sanofi Exendin-4 derivatives as peptidic dual GLP-1/glucagon receptor agonists
EP3134131B1 (en) 2014-04-23 2021-12-22 ModernaTX, Inc. Nucleic acid vaccines
JP2021091689A (ja) * 2014-04-23 2021-06-17 モデルナティーエックス， インコーポレイテッド 核酸ワクチン
US12329812B2 (en) 2014-04-23 2025-06-17 Modernatx, Inc. Nucleic acid vaccines
US12274743B2 (en) 2014-04-23 2025-04-15 Modernatx, Inc. Nucleic acid vaccines
US9850269B2 (en) 2014-04-25 2017-12-26 Translate Bio, Inc. Methods for purification of messenger RNA
US10155785B2 (en) 2014-04-25 2018-12-18 Translate Bio, Inc. Methods for purification of messenger RNA
US11884692B2 (en) 2014-04-25 2024-01-30 Translate Bio, Inc. Methods for purification of messenger RNA
US11059841B2 (en) 2014-04-25 2021-07-13 Translate Bio, Inc. Methods for purification of messenger RNA
US12060381B2 (en) 2014-04-25 2024-08-13 Translate Bio, Inc. Methods for purification of messenger RNA
US10493166B2 (en) 2014-05-30 2019-12-03 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US11433144B2 (en) 2014-05-30 2022-09-06 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10022455B2 (en) 2014-05-30 2018-07-17 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10286082B2 (en) 2014-05-30 2019-05-14 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10293057B2 (en) 2014-05-30 2019-05-21 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10286083B2 (en) 2014-05-30 2019-05-14 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US10912844B2 (en) 2014-05-30 2021-02-09 Translate Bio, Inc. Biodegradable lipids for delivery of nucleic acids
US9932381B2 (en) 2014-06-18 2018-04-03 Sanofi Exendin-4 derivatives as selective glucagon receptor agonists
US10286086B2 (en) 2014-06-19 2019-05-14 Modernatx, Inc. Alternative nucleic acid molecules and uses thereof
US11104652B2 (en) 2014-06-24 2021-08-31 Translate Bio, Inc. Stereochemically enriched compositions for delivery of nucleic acids
US10138213B2 (en) 2014-06-24 2018-11-27 Translate Bio, Inc. Stereochemically enriched compositions for delivery of nucleic acids
US9668980B2 (en) 2014-07-02 2017-06-06 Rana Therapeutics, Inc. Encapsulation of messenger RNA
US10407683B2 (en) 2014-07-16 2019-09-10 Modernatx, Inc. Circular polynucleotides
EP4159741A1 (en) 2014-07-16 2023-04-05 ModernaTX, Inc. Method for producing a chimeric polynucleotide encoding a polypeptide having a triazole-containing internucleotide linkage
US10766943B2 (en) 2014-08-29 2020-09-08 Gemoab Monoclonals Gmbh Universal chimeric antigen expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders
US10611814B2 (en) 2014-08-29 2020-04-07 Gemoab Monoclonals Gmbh Universal chimeric antigen expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders
US12220484B2 (en) 2014-09-25 2025-02-11 BioNTech SE Stable formulations of lipids and liposomes
US11173120B2 (en) 2014-09-25 2021-11-16 Biontech Rna Pharmaceuticals Gmbh Stable formulations of lipids and liposomes
US11998601B2 (en) 2014-12-05 2024-06-04 Translate Bio, Inc. Messenger RNA therapy for treatment of articular disease
US10864267B2 (en) 2014-12-05 2020-12-15 Translate Bio, Inc. Messenger RNA therapy for treatment of articular disease
US9943595B2 (en) 2014-12-05 2018-04-17 Translate Bio, Inc. Messenger RNA therapy for treatment of articular disease
US12435372B2 (en) 2014-12-19 2025-10-07 The Broad Institute, Inc. Methods for profiling the T-cell-receptor repertoire
US20230095010A1 (en) * 2015-01-19 2023-03-30 Technion Research & Development Foundation Limited. Ubiquitin ligase kpc1 promotes processing of p105 nf-kappab1 to p50, eliciting strong tumor suppression
US11156617B2 (en) 2015-02-12 2021-10-26 BioNTech RNA Pharmaceuticals GbmH Predicting T cell epitopes useful for vaccination
US11712463B2 (en) 2015-03-19 2023-08-01 Translate Bio, Inc. MRNA therapy for pompe disease
US10172924B2 (en) 2015-03-19 2019-01-08 Translate Bio, Inc. MRNA therapy for pompe disease
US11090368B2 (en) 2015-03-19 2021-08-17 Translate Bio, Inc. MRNA therapy for Pompe disease
US10806797B2 (en) 2015-06-05 2020-10-20 Sanofi Prodrugs comprising an GLP-1/glucagon dual agonist linker hyaluronic acid conjugate
US11391744B2 (en) 2015-06-08 2022-07-19 Arquer Diagnostic Limited Methods and kits
US11519916B2 (en) 2015-06-08 2022-12-06 Arquer Diagnostics Limited Methods for analysing a urine sample
US9982029B2 (en) 2015-07-10 2018-05-29 Sanofi Exendin-4 derivatives as selective peptidic dual GLP-1/glucagon receptor agonists
US12109274B2 (en) 2015-09-17 2024-10-08 Modernatx, Inc. Polynucleotides containing a stabilizing tail region
US12071620B2 (en) 2015-09-17 2024-08-27 Modernatx, Inc. Polynucleotides containing a morpholino linker
US11434486B2 (en) 2015-09-17 2022-09-06 Modernatx, Inc. Polynucleotides containing a morpholino linker
US10849920B2 (en) 2015-10-05 2020-12-01 Modernatx, Inc. Methods for therapeutic administration of messenger ribonucleic acid drugs
US12173043B2 (en) 2015-10-05 2024-12-24 Immatics Biotechnologies Gmbh Peptides and combination of peptides for use in immunotherapy against small cell lung cancer and other cancers
US12246030B2 (en) 2015-10-05 2025-03-11 Modernatx, Inc. Methods for therapeutic administration of messenger ribonucleic acid drugs
US11590157B2 (en) 2015-10-05 2023-02-28 Modernatx, Inc. Methods for therapeutic administration of messenger ribonucleic acid drugs
US11492628B2 (en) 2015-10-07 2022-11-08 BioNTech SE 3′-UTR sequences for stabilization of RNA
US10144942B2 (en) 2015-10-14 2018-12-04 Translate Bio, Inc. Modification of RNA-related enzymes for enhanced production
US10995354B2 (en) 2015-10-14 2021-05-04 Translate Bio, Inc. Modification of RNA-related enzymes for enhanced production
JP2018532777A (ja) * 2015-10-22 2018-11-08 モデルナティーエックス， インコーポレイテッド 癌ワクチン
EP3964200A1 (en) * 2015-12-10 2022-03-09 ModernaTX, Inc. Compositions and methods for delivery of therapeutic agents
US10556018B2 (en) 2015-12-10 2020-02-11 Modernatx, Inc. Compositions and methods for delivery of agents
US10485885B2 (en) 2015-12-10 2019-11-26 Modernatx, Inc. Compositions and methods for delivery of agents
US10207010B2 (en) 2015-12-10 2019-02-19 Modernatx, Inc. Compositions and methods for delivery of agents
US11285222B2 (en) 2015-12-10 2022-03-29 Modernatx, Inc. Compositions and methods for delivery of agents
US12491260B2 (en) 2015-12-10 2025-12-09 Modernatx, Inc. Compositions and methods for delivery of agents
WO2017127750A1 (en) * 2016-01-22 2017-07-27 Modernatx, Inc. Messenger ribonucleic acids for the production of intracellular binding polypeptides and methods of use thereof
RU2773273C2 (ru) * 2016-03-31 2022-06-01 БАЙОНТЕК ЮЭс ИНК. Неоантигены и способы их использования
WO2017173321A1 (en) * 2016-03-31 2017-10-05 Neon Therapeutics, Inc. Neoantigens and methods of their use
US11124804B2 (en) 2016-04-08 2021-09-21 Translate Bio, Inc. Multimeric coding nucleic acid and uses thereof
US10266843B2 (en) 2016-04-08 2019-04-23 Translate Bio, Inc. Multimeric coding nucleic acid and uses thereof
US10428349B2 (en) 2016-04-08 2019-10-01 Translate Bio, Inc. Multimeric coding nucleic acid and uses thereof
US11000573B2 (en) 2016-05-18 2021-05-11 Modernatx, Inc. Polynucleotides encoding interleukin-12 (IL12) and uses thereof
US11311602B2 (en) 2016-05-18 2022-04-26 Modernatx, Inc. Polynucleotides encoding interleukin-12 (IL12) and uses thereof
US12128113B2 (en) 2016-05-18 2024-10-29 Modernatx, Inc. Polynucleotides encoding JAGGED1 for the treatment of Alagille syndrome
US11571463B2 (en) 2016-05-18 2023-02-07 Modernatx, Inc. Polynucleotides encoding interleukin-12 (IL12) and uses thereof
US10646549B2 (en) 2016-05-18 2020-05-12 Modernatx, Inc. Polynucleotides encoding interleukin-12 (IL12) and uses thereof
US10835583B2 (en) 2016-06-13 2020-11-17 Translate Bio, Inc. Messenger RNA therapy for the treatment of ornithine transcarbamylase deficiency
US12201677B2 (en) 2016-06-13 2025-01-21 Translate Bio, Inc. Messenger RNA therapy for the treatment of ornithine transcarbamylase deficiency
US12385034B2 (en) 2016-06-24 2025-08-12 Modernatx, Inc. Methods and apparatus for filtration
WO2018009838A1 (en) 2016-07-07 2018-01-11 Rubius Therapeutics, Inc. Compositions and methods related to therapeutic cell systems expressing exogenous rna
US20190175690A1 (en) * 2016-08-16 2019-06-13 Children's Medical Center Corporation Compositions and methods for cardiac repair
US11207382B2 (en) 2016-08-19 2021-12-28 University Of Florida Research Foundation, Incorporated Compositions for treating conditions using recombinant self-complementary adeno-associated virus
WO2018035451A1 (en) 2016-08-19 2018-02-22 Calimmune, Inc. Methods and compositions for treating conditions using recombinant self-complementary adeno-associated virus
EP3515466A4 (en) * 2016-09-21 2020-05-27 The Trustees of The University of Pennsylvania OPTIMIZED SYNTHETIC INMUNOGENOUS CONSENSUS COMPOSITIONS AGAINST FIBROBLAST ACTIVATION PROTEIN
CN110167576A (zh) * 2016-09-21 2019-08-23 威斯塔解剖学和生物学研究所 靶向成纤维细胞活化蛋白的优化的合成共有免疫原性组合物
US12409218B2 (en) 2016-11-11 2025-09-09 Modernatx, Inc. Influenza vaccine
US12318443B2 (en) 2016-11-11 2025-06-03 Modernatx, Inc. Influenza vaccine
US11958886B2 (en) 2016-12-07 2024-04-16 University Of Florida Research Foundation, Incorporated IL-1RA cDNAs
US11464836B2 (en) 2016-12-08 2022-10-11 Curevac Ag RNA for treatment or prophylaxis of a liver disease
EP3808380A1 (en) * 2016-12-08 2021-04-21 CureVac AG Rna for treatment or prophylaxis of a liver disease
WO2018104538A1 (en) * 2016-12-08 2018-06-14 Curevac Ag Rna for treatment or prophylaxis of a liver disease
JP2020506189A (ja) * 2017-02-01 2020-02-27 モデルナティーエックス， インコーポレイテッド Ｒｎａ癌ワクチン
WO2018157009A1 (en) * 2017-02-24 2018-08-30 Modernatx, Inc. Nucleic acid-based therapy of muscular dystrophies
US11253605B2 (en) 2017-02-27 2022-02-22 Translate Bio, Inc. Codon-optimized CFTR MRNA
US12303561B2 (en) 2017-04-03 2025-05-20 Biontech Us Inc. Protein antigens and uses thereof
US12428653B2 (en) 2017-05-11 2025-09-30 The Trustees Of The University Of Pennsylvania Gene therapy for ceroid lipofuscinoses
US11591614B2 (en) 2017-05-11 2023-02-28 The Trustees Of The University Of Pennsylvania Gene therapy for ceroid lipofuscinoses
US11173190B2 (en) 2017-05-16 2021-11-16 Translate Bio, Inc. Treatment of cystic fibrosis by delivery of codon-optimized mRNA encoding CFTR
US11873327B2 (en) 2017-05-18 2024-01-16 Modernatx, Inc. Polynucleotides encoding tethered interleukin-12 (IL12) polypeptides and uses thereof
US12270813B2 (en) 2017-06-09 2025-04-08 BioNTech SE Methods for predicting the usefulness of disease specific amino acid modifications for immunotherapy
WO2018231990A2 (en) 2017-06-14 2018-12-20 Modernatx, Inc. Polynucleotides encoding methylmalonyl-coa mutase
US11419951B2 (en) 2017-08-19 2022-08-23 Ohio State Innovation Foundation Peptide-based cancer imaging agents
WO2019040367A1 (en) * 2017-08-19 2019-02-28 Ohio State Innovation Foundation NEW CANCER IMAGING AGENTS BASED ON PEPTIDES
US12064473B2 (en) 2017-12-13 2024-08-20 Inovio Pharmaceuticals, Inc. Cancer vaccines targeting Survivin and uses thereof
RU2776949C2 (ru) * 2017-12-13 2022-07-29 Иновио Фармасьютикалз, Инк. Противораковые вакцины, нацеленные на сурвивин, и их применения
RU2751253C1 (ru) * 2017-12-13 2021-07-12 Иновио Фармасьютикалз, Инк. Противораковые вакцины, нацеленные на сурвивин, и их применения
WO2019118766A3 (en) * 2017-12-13 2019-09-19 Inovio Pharmaceuticals, Inc. Cancer vaccines targeting survivin and uses thereof
US12357653B2 (en) 2017-12-15 2025-07-15 Flagship Pioneering Innovations Vi, Llc Compositions comprising circular polyribonucleotides and uses thereof
US11844759B2 (en) 2017-12-15 2023-12-19 Flagship Pioneering Innovations Vi, Llc Compositions comprising circular polyribonucleotides and uses thereof
US11793867B2 (en) 2017-12-18 2023-10-24 Biontech Us Inc. Neoantigens and uses thereof
US11167043B2 (en) 2017-12-20 2021-11-09 Translate Bio, Inc. Composition and methods for treatment of ornithine transcarbamylase deficiency
US12268754B2 (en) 2017-12-20 2025-04-08 Translate Bio, Inc. Composition and methods for treatment of ornithine transcarbamylase deficiency
US20210000975A1 (en) * 2018-03-07 2021-01-07 Icahn School Of Medicine At Mount Sinai Modrna encoding sphingolipid-metabolizing proteins
US12194108B2 (en) 2018-03-23 2025-01-14 University Of Massachusetts Gene therapeutics for treating bone disorders
EP4169528A1 (en) 2018-04-11 2023-04-26 Enterome S.A. Antigenic peptides for prevention and treatment of cancer
WO2019197567A2 (en) 2018-04-11 2019-10-17 Enterome S.A. Antigenic peptides for prevention and treatment of cancer
US11905321B2 (en) 2018-06-05 2024-02-20 The Trustees Of The University Of Pennsylvania Compositions and methods of muscle specific kinase chimeric autoantibody receptor cells
WO2019236593A1 (en) * 2018-06-05 2019-12-12 The Trustees Of The University Of Pennsylvania Compositions and methods of muscle specific kinase chimeric autoantibody receptor cells
US12246067B2 (en) 2018-06-19 2025-03-11 Biontech Us Inc. Neoantigens and uses thereof
US11174500B2 (en) 2018-08-24 2021-11-16 Translate Bio, Inc. Methods for purification of messenger RNA
US12084702B2 (en) 2018-08-24 2024-09-10 Translate Bio, Inc. Methods for purification of messenger RNA
US12383508B2 (en) 2018-09-19 2025-08-12 Modernatx, Inc. High-purity peg lipids and uses thereof
US12151029B2 (en) 2018-09-19 2024-11-26 Modernatx, Inc. PEG lipids and uses thereof
US12195505B2 (en) 2018-11-21 2025-01-14 Translate Bio, Inc. Treatment of cystic fibrosis by delivery of nebulized mRNA encoding CFTR
US11793843B2 (en) 2019-01-10 2023-10-24 Janssen Biotech, Inc. Prostate neoantigens and their uses
US20220133911A1 (en) * 2019-02-14 2022-05-05 Cambridge Enterprise Limited Myc, cyclin t1 and/or cdk9 for use in the treatment of degenerative heart and cns disorders
US12480117B2 (en) 2019-03-25 2025-11-25 Flagship Pioneering Innovations Vi, Llc Compositions comprising modified circular polyribonucleotides and uses thereof
EP3966232A4 (en) * 2019-05-08 2023-06-07 The Feinstein Institutes for Medical Research Interferon regulatory factor 5 inhibitors and uses thereof
US12351610B2 (en) 2019-05-08 2025-07-08 The Feinstein Institutes For Medical Research Interferon regulatory factor 5 inhibitors and uses thereof
WO2020227194A1 (en) * 2019-05-08 2020-11-12 The Feinstein Institutes For Medical Research Interferon regulatory factor 5 inhibitors and uses thereof
WO2021094562A2 (en) 2019-11-15 2021-05-20 Enterome S.A. Antigenic peptides for prevention and treatment of b-cell malignancy
EP4357356A2 (en) 2019-11-15 2024-04-24 Enterome S.A. Antigenic peptides for prevention and treatment of b-cell malignancy
US11951185B2 (en) 2020-04-22 2024-04-09 BioNTech SE RNA constructs and uses thereof
US11779659B2 (en) 2020-04-22 2023-10-10 BioNTech SE RNA constructs and uses thereof
US12133899B2 (en) 2020-04-22 2024-11-05 BioNTech SE Coronavirus vaccine
US11547673B1 (en) 2020-04-22 2023-01-10 BioNTech SE Coronavirus vaccine
US11925694B2 (en) 2020-04-22 2024-03-12 BioNTech SE Coronavirus vaccine
US20210330740A1 (en) * 2020-04-23 2021-10-28 Run-X Corporation Runx3 modified protein for prevention or treatment of cancer
US12414980B2 (en) 2020-04-23 2025-09-16 Genecraft, Inc. Pharmaceutical composition comprising RUNX3 protein and CDK4 inhibitor or mTOR inhibitor cotreatment for prevention or treatment of cancer
US11931401B2 (en) * 2020-04-23 2024-03-19 Genecraft Inc. Runx3 modified protein for prevention or treatment of cancer
US12295997B2 (en) 2020-07-06 2025-05-13 Janssen Biotech, Inc. Prostate neoantigens and their uses
WO2022009049A1 (en) * 2020-07-06 2022-01-13 Janssen Biotech, Inc. Prostate neoantigens and their uses
WO2022040275A1 (en) * 2020-08-19 2022-02-24 University Of Massachusetts Development of novel gene therapeutics inflammation-induced bone loss
US12419948B2 (en) 2020-08-31 2025-09-23 The Broad Institute, Inc. Immunogenic compositions and use thereof
EP4046629A1 (en) 2021-02-19 2022-08-24 ModernaTX, Inc. Lipid nanoparticle compositions and methods of formulating the same
KR102818854B1 (ko) 2021-07-29 2025-06-13 주식회사 에스엠엘바이오팜 발현 시스템 및 이를 이용한 핵산 기반 백신
KR20230018284A (ko) * 2021-07-29 2023-02-07 주식회사 에스엠엘바이오팜 발현 시스템 및 이를 이용한 핵산 기반 백신
WO2023031394A1 (en) 2021-09-03 2023-03-09 CureVac SE Novel lipid nanoparticles for delivery of nucleic acids
WO2023039654A3 (pt) * 2021-09-17 2023-05-04 Fundação Oswaldo Cruz Aptâmero de ácido nucleico, composição, uso de um aptâmero, kit diagnóstico, método para detectar ou diagnosticar um tumor, e, método para tratamento de câncer
WO2023069498A1 (en) 2021-10-22 2023-04-27 Senda Biosciences, Inc. Mrna vaccine composition
WO2023073228A1 (en) 2021-10-29 2023-05-04 CureVac SE Improved circular rna for expressing therapeutic proteins
WO2023096858A1 (en) 2021-11-23 2023-06-01 Senda Biosciences, Inc. A bacteria-derived lipid composition and use thereof
US12186387B2 (en) 2021-11-29 2025-01-07 BioNTech SE Coronavirus vaccine
US12208136B2 (en) 2021-11-29 2025-01-28 BioNTech SE Coronavirus vaccine
WO2023122080A1 (en) 2021-12-20 2023-06-29 Senda Biosciences, Inc. Compositions comprising mrna and lipid reconstructed plant messenger packs
WO2023144330A1 (en) 2022-01-28 2023-08-03 CureVac SE Nucleic acid encoded transcription factor inhibitors
WO2023150743A3 (en) * 2022-02-07 2023-09-21 Aavogen Inc. Codon-optimized smad7 gene therapy to treat and prevent muscle wasting and to enhance muscle mass
WO2023177904A1 (en) 2022-03-18 2023-09-21 Modernatx, Inc. Sterile filtration of lipid nanoparticles and filtration analysis thereof for biological applications
WO2023187127A1 (en) 2022-03-31 2023-10-05 Enterome S.A. Antigenic peptides for prevention and treatment of cancer
WO2023197001A3 (en) * 2022-04-07 2023-11-16 The Board Of Regents Of The University Of Texas System Compositions and methods for treating liver diseases with sirnas targeting cideb
WO2023227608A1 (en) 2022-05-25 2023-11-30 Glaxosmithkline Biologicals Sa Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide
US12509666B2 (en) 2022-06-01 2025-12-30 Translate Bio, Inc. MRNA therapy for phenylketonuria
US11878055B1 (en) 2022-06-26 2024-01-23 BioNTech SE Coronavirus vaccine
WO2024044147A1 (en) 2022-08-23 2024-02-29 Modernatx, Inc. Methods for purification of ionizable lipids
DE202023106198U1 (de) 2022-10-28 2024-03-21 CureVac SE Impfstoff auf Nukleinsäurebasis
WO2024097521A3 (en) * 2022-11-03 2024-06-13 University Of Massachusetts Compositions for treatment of osteogenesis imperfecta
WO2024102434A1 (en) 2022-11-10 2024-05-16 Senda Biosciences, Inc. Rna compositions comprising lipid nanoparticles or lipid reconstructed natural messenger packs
WO2024159172A1 (en) 2023-01-27 2024-08-02 Senda Biosciences, Inc. A modified lipid composition and uses thereof
WO2024163335A3 (en) * 2023-01-30 2024-10-03 The Board Of Regents Of The University Of Texas System Pten gene therapy vectors and uses thereof
WO2024171063A1 (en) * 2023-02-13 2024-08-22 AstraZeneca Ireland Limited Nucleic acids encoding bcl2-associated athanogene 3 (bag3) for gene therapy
WO2024184500A1 (en) 2023-03-08 2024-09-12 CureVac SE Novel lipid nanoparticle formulations for delivery of nucleic acids
WO2024220712A2 (en) 2023-04-19 2024-10-24 Sail Biomedicines, Inc. Vaccine compositions
WO2024220625A1 (en) 2023-04-19 2024-10-24 Sail Biomedicines, Inc. Delivery of polynucleotides from lipid nanoparticles comprising rna and ionizable lipids
WO2024220752A2 (en) 2023-04-19 2024-10-24 Sail Biomedicines, Inc. Rna therapeutic compositions
WO2024230934A1 (en) 2023-05-11 2024-11-14 CureVac SE Therapeutic nucleic acid for the treatment of ophthalmic diseases
WO2024238726A1 (en) 2023-05-16 2024-11-21 Omega Therapeutics, Inc. Methods and compositions for modulating methylation of a target gene
WO2024238723A1 (en) 2023-05-16 2024-11-21 Omega Therapeutics, Inc. Methods and compositions for modulating pcsk9 expression
WO2025019742A1 (en) 2023-07-19 2025-01-23 Omega Therapeutics, Inc. Methods and compositions for modulating ctnnb1 expression
WO2025059215A1 (en) 2023-09-12 2025-03-20 Aadigen, Llc Methods and compositions for treating or preventing cancer
WO2025072383A1 (en) 2023-09-25 2025-04-03 The Broad Institute, Inc. Viral open reading frames, uses thereof, and methods of detecting the same
WO2025097055A2 (en) 2023-11-02 2025-05-08 The Broad Institute, Inc. Compositions and methods of use of t cells in immunotherapy
WO2025194138A1 (en) 2024-03-14 2025-09-18 Tessera Therapeutics, Inc. St1cas9 compositions and methods for modulating a genome
WO2025235563A1 (en) 2024-05-07 2025-11-13 Omega Therapeutics, Inc. Epigenetic modulation for upregulation of genes
US12502431B2 (en) 2024-08-30 2025-12-23 Modernatx, Inc. Delivery and formulation of engineered nucleic acids

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