Patents by Inventor Shi-Lung Lin

Shi-Lung Lin has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20230295627
    Abstract: This invention generally relates to a novel composition of RNA/mRNA medicines as well as vaccines produced by using replicase- and/or RNA-dependent RNA polymerase (RdRp)-mediated RNA cycling reaction (RCR). The present invention is useful for developing a variety of self-amplifying RNA/mRNA (samRNA) medicines and vaccines containing at least a replicase/RdRp-binding site in the 5?- or 3?-end, or both, of any desired RNA molecule, including but not limited to antisense RNA (aRNA), small interferring RNA (siRNA), short hairpin RNA (shRNA), microRNA (miRNA)/miRNA precursor, long non-coding RNA (lnRNA) and mRNA. These RNA molecules can be either in single-stranded or in double-stranded, or mixed, conformation. The samRNA so obtained is useful not only for producing RNA-based vaccines and/or medicines but also for generating the mRNA-associated proteins, peptides, and/or antibodies under a proper in-vitro or in-cell translation condition.
    Type: Application
    Filed: January 18, 2023
    Publication date: September 21, 2023
    Inventors: Shi-Lung Lin, Sam Lin, Chun-Hung Lin
  • Publication number: 20230242958
    Abstract: Disclosed herein is directed to a synthetic ribonucleic acid (RNA) fragment that includes an RNA template flanked by at least of 5?-end RNA-dependent RNA polymerase (RdRp) binding site and a 3?-end RdRp binding site, thus the synthetic RNA fragment can be amplified in vitro via an RNA-dependent RNA cycling reaction (RCR). Also disclosed herein is a method for producing an amplified RNA product by use of the present synthetic RNA fragment.
    Type: Application
    Filed: January 19, 2023
    Publication date: August 3, 2023
    Applicant: MELLO BIOTECH TAIWAN CO., LTD.
    Inventors: Shi-Lung LIN, Sam LIN, David TS WU
  • Patent number: 11624067
    Abstract: This invention generally relates to a composition and its method of use for inducing adult stem cell (ASC) expansion and/or derivation in vitro, using miR-302-like pre-miRNAs, shRNAs and/or siRNAs, all of which contain a shared sequence of 5?-UAAGUGCUUC CAUGUUU-3? (SEQ ID NO: 7) in the 5?-end, and further in conjunction with the use of some wound-healing-related defined factors, including but not limited to basic fibroblast growth factor (bFGF)/fibroblast growth factor 2 (FGF-2), leukemia inhibitory factor (LIF), insulin-like growth factor (IGF), Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF), tumor necrosis factor (TNF), stem cell factor (SCF), homeobox proteins (HOX), Notch, GSK, Wnt/beta-Catenin signals, interleukins, and/or bone morphogenetic proteins (BMPs).
    Type: Grant
    Filed: September 19, 2018
    Date of Patent: April 11, 2023
    Inventors: Shi-Lung Lin, Samantha Chang-Lin, Donald Chang
  • Publication number: 20230099592
    Abstract: This invention relates to a novel composition and method for RNA/mRNA production as well as amplification using viral RNA replicase and/or RNA-dependent RNA polymerase (RdRp) enzymes and the use of associated RNA/mRNA products thereof. The present invention can be used for manufacturing and amplifying all varieties of RNA/mRNA sequences carrying at least a replicase/RdRp-binding site in the 5?- or 3?-end, or both. The RNA/mRNA so obtained is useful for not only producing mRNA vaccines and/or RNA-based medicines but for generating the mRNA-associated proteins, peptides, and/or antibodies under an in-vitro as well as in-cell translation condition. Principally, the present invention is a novel RNA replicase/RdRp-mediated RNA/mRNA amplification method, namely Replicase Cycling Reaction (RCR). The RNA replicases involved in RCR include but not limited to viral and/or bacteriophage RNA-dependent RNA polymerases (RdRp) in either modified or non-modified mRNA and/or protein compositions, particularly coronaviral (e.
    Type: Application
    Filed: September 7, 2022
    Publication date: March 30, 2023
    Inventors: Shi-Lung LIN, Sam Lin, Chun-Hung Lin
  • Publication number: 20220411848
    Abstract: This invention generally relates to a novel RNA/mRNA production and amplification method using viral RNA replicase and/or RNA-dependent RNA polymerase (RdRp) enzymes as well as the associated mRNAs thereof. The present invention can be used for manufacturing and amplifying all varieties of RNA/mRNA sequences carrying at least an RdRp-binding site in the 5?- or 3?-end, or both. The RNA/mRNA so obtained is useful for not only producing mRNA vaccines and/or RNA-based medicines but also for generating the mRNA-associated proteins, peptides, and/or antibodies under an in-vitro as well as in-cell translation condition. Principally, the present invention is a novel RNA replicase-mediated RNA/mRNA amplification method, namely Replicase Cycling Reaction (RCR). The RNA replicases involved in RCR include but not limited to viral and/or bacteriophage RNA-dependent RNA polymerases (RdRp), particularly coronaviral and hepatitis C viral (HCV) RdRp enzymes.
    Type: Application
    Filed: January 19, 2022
    Publication date: December 29, 2022
    Inventors: Shi-Lung LIN, Sam LIN, Chun-Hung LIN
  • Publication number: 20220396798
    Abstract: This invention relates to a novel mRNA composition and its production method useful for developing and manufacturing RNA-based anti-viral and/or anti-cancer vaccines and medicines. This invention includes two types of mRNA constructs, namely “5?-hairpin messenger RNA (5hmRNA)” and “messenger-hairpin-messenger RNA (mhmRNA)”, respectively. Both of 5hmRNA and mhmRNA contain at least a hairpin-like stem-loop RNA structure. The 5hmRNA contains at least a stem-loop RNA structure in the 5?-UTR of a protein/peptide-coding mRNA, while the mhmRNA contains a middle stem-loop structure flanked with two protein/peptide-coding mRNA sequences on both sides. In mhmRNA, the first 5?-mRNA preferably encodes an RNA replicase, for amplifying the second 3?-mRNA in transfected cells. After transfection into target cells, 5hmRNA and mhmRNA can be further translated into at least a desired protein/peptide.
    Type: Application
    Filed: September 29, 2021
    Publication date: December 15, 2022
    Inventors: Shi-Lung LIN, Samantha CHANG-LIN, Jack SK CHEN, David TS WU, Chia-Ning SHEN, Mei-Jung WANG
  • Publication number: 20220396778
    Abstract: This invention generally relates to a novel RNA composition and its production method useful for generating and expanding induced pluripotent stem cells (iPS cells; iPSC) as well as adult stem cells (ASC). The RNA composition so defined can be used for producing not only non-transgenic but also tumor-free iPS cells. The defined RNA composition contans at least two types of different RNA constructs; one is “miR-302 precursor RNA (pre-miR-302)” and the other is “RNA-dependent RNA polymerase (RdRp)” mRNA. Both of pre-miR-302 and RdRp mRNA contain highly structured RNA comformations, such as hairpin and stem-loop structures. To produce highly structured RNAs, a novel PCR-IVT methodology has been developed and used with a specially designed RNA polymerase-helicase mixture activity.
    Type: Application
    Filed: January 19, 2022
    Publication date: December 15, 2022
    Inventors: Shi-Lung LIN, Sam LIN, Chun-Hung LIN
  • Patent number: 11326164
    Abstract: This invention generally relates to a group of novel chemical compositions and their use for formulating RNA- and/or DNA-based medicine drugs/vaccines into stable compound complexes useful for both in-vitro and in-vivo delivery. Particularly, the present invention teaches the synthesis of a group of novel trimethylglycyl chemicals and their use for formulating cosmetic, therapeutic- and/or pharmaceutical-grade nucleic acid compositions, including but not limited microRNA precursors (pre-miRNA/miRNA), small hairpin RNAs (shRNA), short interfering RNAs (siRNA), ribozymes, antisense oligonucleotides, RNA-DNA hybrids and DNA-based vectors/vaccines, with or without modification, into delivery complexes, which can then be absorbed by cells in vivo, ex vivo and/or in vitro through an active mechanism of endocytosis via acetylcoline receptors for releasing the therapeutic and pharmaceutical effects of the formulated nucleic acid compositions.
    Type: Grant
    Filed: March 20, 2020
    Date of Patent: May 10, 2022
    Inventors: Shi-Lung Lin, Samantha Chang-Lin, Chin-Tsyh Donald Chang
  • Publication number: 20210095280
    Abstract: This invention generally relates to a group of novel chemical compositions and their use for formulating RNA- and/or DNA-based medicine drugs/vaccines into stable compound complexes useful for both in-vitro and in-vivo delivery. Particularly, the present invention teaches the synthesis of a group of novel trimethylglycyl chemicals and their use for formulating cosmetic, therapeutic- and/or pharmaceutical-grade nucleic acid compositions, including but not limited microRNA precursors (pre-miRNA/miRNA), small hairpin RNAs (shRNA), short interfering RNAs (siRNA), ribozymes, antisense oligonucleotides, RNA-DNA hybrids and DNA-based vectors/vaccines, with or without modification, into delivery complexes, which can then be absorbed by cells in vivo, ex vivo and/or in vitro through an active mechanism of endocytosis via acetylcoline receptors for releasing the therapeutic and pharmaceutical effects of the formulated nucleic acid compositions.
    Type: Application
    Filed: March 20, 2020
    Publication date: April 1, 2021
    Applicants: WJWU & LYNN Institute for Stem Cell Research, Mello Biotech Taiwan Co., Ltd.
    Inventors: Shi-Lung Lin, Samantha Chang-Lin, Chin-Tsyh Donald Chang
  • Publication number: 20200318110
    Abstract: This invention generally relates to a composition and method of using man-made small RNAs, such as small interfering RNAs (siRNA), microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA), as tumor suppressing anti-cancer drugs for treating human tumors and cancers, in particular, but not limited, for treating skin (melanoma), blood (leukemia), prostate, breast, liver and lung cancers as well as various neoplastic tumors, such as brain tumors and teratocarcinomas that contain a variety of tumorous and cancerous cells derived from all three germ layers of tissues, including ectoderm, mesoderm and endoderm. More specifically, the present invention relates to the use of miR-302-like siRNA (siR-302) and/or miR-302 precursors (pre-miR-302) for developing novel medicines and therapies against a variety of human cancers, in particular lung cancers.
    Type: Application
    Filed: February 24, 2017
    Publication date: October 8, 2020
    Inventors: Shi-Lung LIN, David TS WU
  • Publication number: 20200165607
    Abstract: This invention generally relates to a composition and method of using mam-made small RNAs, such as small interfering RNAs (siRNA), microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA), as tumor suppressing anti-cancer drugs for treating human tumors and cancers, in particular, but not limited, for treating skin (melanoma), blood (leukemia), prostate, breast, liver and lung cancers as well as various neoplastic tumors, such as brain tumors and teratocarcinomas that contain a variety of tumorous and cancerous cells derived from all three germ layers of tissues, including ectoderm, mesoderm and endoderm. More specifically, the present invention relates to the use of miR-302-like siRNA (siR-302) and/or miR-302 precursors (pre-miR-302) for developing novel medicines and therapies against a variety of human cancers, in particular lung cancers.
    Type: Application
    Filed: August 5, 2019
    Publication date: May 28, 2020
    Inventors: Shi-Lung Lin, Donald C. Chang, David TS Wu, Hsuan-Hsuan Lu
  • Publication number: 20200071700
    Abstract: This invention generally relates to a composition and method of using recombinant microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA) as therapeutic drugs for treating Alzheimer's diseases (AD). More specifically, the present invention relates to the use of man-made miRNA miR-302 precursors (pre-miR-302) for AD therapy in humans. These pre-miR-302 molecules can be mass produced in prokaryotes as a form of DNA expression-competent DNA vectors and/or hairpin-like RNAs. As prokaryotic cells do not transcribe or process hairpin-like RNAs, the present invention also teaches a method for expressing pre-miRNAs in prokaryotes, i.e. pro-miRNA, using a novel hairpin-like RNA transcription mechanism newly found in prokaryotes.
    Type: Application
    Filed: November 18, 2019
    Publication date: March 5, 2020
    Inventors: Chih-Li LIN, Hsin-Hua LI, Shi-Lung LIN, Te-Jen LAI
  • Patent number: 10519440
    Abstract: This invention generally relates to a composition and method of using recombinant microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA) as therapeutic drugs for treating Alzheimer's diseases (AD). More specifically, the present invention relates to the use of man-made miRNA miR-302 precursors (pre-miR-302) for AD therapy in humans. These pre-miR-302 molecules can be mass produced in prokaryotes as a form of DNA expression-competent DNA vectors and/or hairpin-like RNAs. As prokaryotic cells do not transcribe or process hairpin-like RNAs, the present invention also teaches a method for expressing pre-miRNAs in prokaryotes, i.e. pro-miRNA, using a novel hairpin-like RNA transcription mechanism newly found in prokaryotes.
    Type: Grant
    Filed: February 19, 2016
    Date of Patent: December 31, 2019
    Inventors: Chih-Li Lin, Hsin-Hua Li, Shi-Lung Lin, Te-Jen Lai
  • Patent number: 10370658
    Abstract: This invention generally relates to a composition and method of using mam-made small RNAs, such as small interfering RNAs (siRNA), microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA), as tumor suppressing anti-cancer drugs for treating human tumors and cancers, in particular, but not limited, for treating skin (melanoma), blood (leukemia), prostate, breast, liver and lung cancers as well as various neoplastic tumors, such as brain tumors and teratocarcinomas that contain a variety of tumorous and cancerous cells derived from all three germ layers of tissues, including ectoderm, mesoderm and endoderm. More specifically, the present invention relates to the use of miR-302-like siRNA (siR-302) and/or miR-302 precursors (pre-miR-302) for developing novel medicines and therapies against a variety of human cancers, in particular lung cancers.
    Type: Grant
    Filed: February 24, 2017
    Date of Patent: August 6, 2019
    Inventors: Shi-Lung Lin, Donald C. Chang, David T S Wu, Hsuan-Hsuan Lu
  • Publication number: 20190085335
    Abstract: This invention generally relates to a composition and its method of use for inducing adult stem cell (ASC) expansion and/or derivation in vitro, using miR-302-like pre-miRNAs, shRNAs and/or siRNAs, all of which contain a shared sequence of 5?-UAAGUGCUUC CAUGUUU-3? (SEQ ID NO: 7) in the 5?-end, and further in conjunction with the use of some wound-healing-related defined factors, including but not limited to basic fibroblast growth factor (bFGF)/fibroblast growth factor 2 (FGF-2), leukemia inhibitory factor (LIF), insulin-like growth factor (IGF), Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF), tumor necrosis factor (TNF), stem cell factor (SCF), homeobox proteins (HOX), Notch, GSK, Wnt/beta-Catenin signals, interleukins, and/or bone morphogenetic proteins (BMPs).
    Type: Application
    Filed: September 19, 2018
    Publication date: March 21, 2019
    Inventors: Shi-Lung LIN, Samantha CHANG-LIN, Donald CHANG
  • Patent number: 10196662
    Abstract: This invention generally relates to a composition and its production method useful for developing drugs and/or therapies for enhancing wound healing, in particular scarless wound healing. Particularly, the present invention teaches the essential processes necessary for producing and purifying embryonic stem cell (ESC)-specific RNA compositions, such as messenger RNAs (mRNA), microRNA precursors (pre-miRNA), and small hairpin RNAs (shRNA), which are useful for treating human diseases and lesions.
    Type: Grant
    Filed: January 20, 2015
    Date of Patent: February 5, 2019
    Assignee: MELLO BIOTECHNOLOGY, INC.
    Inventors: David T S Wu, Shi-Lung Lin, Jack S. K. Chen
  • Patent number: 9956196
    Abstract: This invention is related to a novel sugar-like chemical composition and its use for diabetes therapy. Particularly, the present invention teaches the use of monosaccharide-like glycylated sugar alcohol compounds to block or reduce sugar absorption in diabetes patients, so as to prevent the risk of hyperglycemia symptoms. Glycylation of sugar alcohols is a totally novel reaction that has never been reported before. Therefore, the novelty of the present invention is that for the first time glycylated sugar alcohols not only was found but also was found to be useful for treating Diabetes mellitus. In addition, the present invention teaches a method for producing these glycylated sugar alcohols. In sum, the present invention includes not only a kind of novel sugar-like chemical compositions and its use for treating diabetes but also a state-of-the-art protocol and methodology for producing such a novel composition via glycylation of sugars and sugar alcohols.
    Type: Grant
    Filed: December 30, 2014
    Date of Patent: May 1, 2018
    Assignee: WJWU & LYNN INSTITUTE FOR STEM CELL RESEARCH AND MELLO BIOTECHNOLOGY
    Inventors: Shi-Lung Lin, Samantha Chang-Lin, Yi-Wen Lin, Donald Chang
  • Patent number: 9907773
    Abstract: This invention is related to a novel sugar-like chemical composition and its use for diabetes therapy. Particularly, the present invention teaches the use of monosaccharide-like glycylated sugar alcohol compounds to block or reduce sugar absorption in diabetes patients, so as to prevent the risk of hyperglycemia symptoms. Glycylation of sugar alcohols is a totally novel reaction that has never been reported before. Therefore, the novelty of the present invention is that for the first time glycylated sugar alcohols not only was found but also was found to be useful for treating Diabetes mellitus. In addition, the present invention teaches a method for producing these glycylated sugar alcohols. In sum, the present invention includes not only a kind of novel sugar-like chemical compositions and its use for treating diabetes but also a state-of-the-art protocol and methodology for producing such a novel composition via glycylation of sugars and sugar alcohols.
    Type: Grant
    Filed: March 18, 2016
    Date of Patent: March 6, 2018
    Inventors: Shi-Lung Lin, Samantha Chang-Lin, Yi-Wen Lin, Donald Chang
  • Patent number: 9879263
    Abstract: This invention generally relates to a composition and its production method useful for developing drugs/vaccines and/or therapies against a variety of degenerative diseases in humans. Particularly, the present invention teaches the essential steps of production and purification processes necessary for producing small hairpin-like RNA (shRNA) compositions, such as microRNA precursors (pre-miRNA) and short interfering RNAs (siRNA), which are useful for treating human ageing related diseases, such as, but not limited, Alzheimer's diseases, Parkinson's diseases, osteoporosis, diabetes, and cancers. The novelty of the present invention is to create an artificially enhanced adaptation environment for prokaryotic cells to adopt eukaryotic pol-2 and/or pol-2-like promoters for transcribing desired ncRNAs and/or their precursors without going through error-prone prokaryotic promoters, so as to improve the productive efficiency and reading fidelity of the shRNA transcription in the prokaryotic cells.
    Type: Grant
    Filed: May 27, 2016
    Date of Patent: January 30, 2018
    Assignees: MELLO BIOTECHNOLOGY, INC., WJWU & LYNN INSTITUTE FOR STEM CELL RESEARCH
    Inventors: Shi-Lung Lin, Donald Chang, David T S Wu
  • Publication number: 20170342418
    Abstract: This invention generally relates to a composition and its production method useful for developing drugs/vaccines and/or therapies against a variety of degenerative diseases in humans. Particularly, the present invention teaches the essential steps of production and purification processes necessary for producing small hairpin-like RNA (shRNA) compositions, such as microRNA precursors (pre-miRNA) and short interfering RNAs (siRNA), which are useful for treating human ageing related diseases, such as, but not limited, Alzheimer's diseases, Parkinson's diseases, osteoporosis, diabetes, and cancers. The novelty of the present invention is to create an artificially enhanced adaptation environment for prokaryotic cells to adopt eukaryotic pol-2 and/or pol-2-like promoters for transcribing desired ncRNAs and/or their precursors without going through error-prone prokaryotic promoters, so as to improve the productive efficiency and reading fidelity of the shRNA transcription in the prokaryotic cells.
    Type: Application
    Filed: July 27, 2017
    Publication date: November 30, 2017
    Inventors: Shi-Lung LIN, Donald CHANG, David TS WU