Etter litt mere graving dukker det opp noe spennende som kanskje er diskutert før(?) .
Jeg tillater meg å poste den evt igjen, om det er ukjent for noen.
PCI Biotech har en ny søknad på gang – jeg velger å kalle denne PCI-mRNA
[US Patent Application for METHOD Patent Application (Application #20210052628 issued February 25, 2021) - Justia Patents Search 1]
24 Jan, 2019 leverer PCIB patentsøknaden inn.
Dere husker Mr Høgset sin presentasjon ifm SMi RNA Therapeutics 10-11 February 2021 hvor AZ data ble delt?
25 Feb, 2021 velger PCIB å offentliggjøre patentsøknaden. Normal praksis er å holde en søknad utenfor offentligheten opp til 18mnd. PCIB velger i dette tilfelle å offentliggjøre søknaden tidligere. Det som skiller seg ut i denne søknaden er at det er kun Mr Høgset som er oppført, ikke vår kjente støttespiller i Zurich.
Et lite utdrag fra en spennende patenttekst:
In the work leading to the present invention, a specific and new protocol for light-induced mRNA delivery resulting in site-specific protein production has been developed . We show for the first time that potent light-induced protein production is achievable by combining mRNA transfection and PCI. Importantly, we have developed a protocol that is controllable in a time- and site-specific manner. Furthermore, the method avoids the use of transfection agents and the side effects caused by those agents.
The method of the invention is particularly advantageous because it is not a complex method and may be used with a variety of mRNA molecules and target cells/locations. Furthermore, the timing and location of irradiation to release the molecules may be controlled such that it is released only at the time and location that is desired to achieve the required effects. As such, exposure of cells to the various components is minimised, and undesirable side effects are minimised . This is in contrast to the standard techniques for mRNA delivery, where it is not possible to control the timing and location of the release of the various components without the use of targeting agents (which add a further level of complexity).
As described in the Examples herein, a specific protocol has been developed in which very low levels of photosensitiser (approximately 25 to 25,000 times lower than in standard protocols) is used to achieve mRNA delivery. To the best of our knowledge, this is the first teaching of successful (naked) mRNA delivery in vivo using a PCI method .
The mRNA is not associated with a carrier or other molecule, i.e. is not bound or conjugated to or carried by any other component to aid its internalization. Such association includes any connection whether by binding, steric entrapment or other method that connects the molecules together so that they would remain associated under appropriate conditions. Thus no transfection agent or carrier is used. In this sense, the mRNA that is used is naked, i.e. free of associated molecules affecting its internalization. The photosensitising agent that is used with the mRNA in methods described herein does not constitute a carrier or transfection agent for the mRNA.
The wavelength of light to be used is selected according to the photosensitising agent to be used. Light of a wavelength effective to activate the photosensitising agent is able to elicit the production of reactive oxygen species on exposure of the photosensitising agent to that light. Suitable artificial light sources are well known in the art, e.g. using blue (400-475 nm) or red (620-750 nm) wavelength light. For TPCS2a, for example, a wavelength of between 400 and 500 nm, more preferably between 400 and 450 nm, e.g. from 400-435 nm or 420-435 nm, and even more preferably approximately 435 nm, or 435 nm may be used. In the alternative, red light may be used to ensure deeper light penetration, e.g. for tumour tissue. In this case a wavelength of 620-750, e.g. 640-660 nm may be used. Where appropriate the photosensitiser, e.g. a porphyrin or chlorin, may be activated by green light , for example the KillerRed (Evrogen, Moscow, Russia) photosensitiser may be activated by green light.
The expressed polypeptides may act directly in a therapeutic manner (e.g. a cytotoxic molecule) or may initiate a therapeutic response, e.g. a therapeutic immune response. Particularly preferred diseases, disorders or infections to be treated include cancer, cardiovascular disease, autoimmune diseases, cystic fibrosis, neurodegenerative diseases such as Huntington’s disease, Alzheimer’s disease and Parkinson’s disease, viral infections such as influenza, hepatitis (e.g. B and C), HIV and herpes, infections with intracellular or extracellular bacteria, such as in tuberculosis, leprosy, chlamydia, listeria, legionella and cholera and infection by E. coli, P. aeruginosa, S. aureus, Streptococcus spp., N. meningitidis and S. pyogenes , infections by parasites, e.g. in malaria and leishmaniosis and other diseases, disorders or infections discussed herein.
The in vivo uses may be divided into protein therapy, immunotherapy and gene therapy methods.
In protein therapy methods , the mRNA is used to produce a protein that the patient is lacking, e.g. because of an inherited mutation or reduced expression, or which would have a therapeutic effect. In one alternative, this could be e.g. an enzyme, a peptide hormone, a cytokine, a growth factor, a blood clotting factor (in bleeding disorders) or other important proteins. In this case an mRNA encoding the missing protein is delivered to suitable cells in the body (for example in the skin, muscle, liver etc.) so that these cells produce the missing protein that will either act inside the producer cell (e.g. if the mRNA encodes an intracellular enzyme), locally (e.g. to produce a growth factor in a certain tissue) or systemically (e.g. to produce a missing blood clotting factor or a peptide hormone).
In immunotherapy methods the expressed polypeptide is used to generate a therapeutic immune response. This may include prophylactic or therapeutic vaccination methods. Such methods may be used to treat infectious diseases. For example, prophylactic vaccination may be used in which a relevant antigen is used prior to exposure to the infectious agent to generate adaptive immunity to subsequent exposure. Preferred target infectious diseases are typically diseases in which T-cell responses are important. Examples include: viral diseases such as influenza, hepatitis (e.g. B and C), HIV, Herpes and many other viral infections; infections with bacteria (intracellular or extracellular), such as in tuberculosis, leprosy, chlamydia, listeria, legionella and cholera and infection by E. coli, P. aeruginosa, S. aureus, Streptococcus spp., N. meningitidis and S. pyogenes , and several other infections; infections by parasites, e.g. in malaria and leishmaniosis. Appropriate antigens are selected to generate a prophylactic immune response and the encoding mRNA used in methods of the invention.
Gene therapy methods may also be used. As referred to herein gene therapy methods are considered to be methods which introduce or modify one or more gene within a subject or modify the expression of one or more gene in a subject. Thus, by way of example, the mRNA may encode a polypeptide that would assist in altering the subject’s genome. Thus, for example, mRNA which encodes enzymes useful in sequence-specific modification of the chromosomal DNA in the target cells may be used, e.g. to corrected a mutated gene or to insert a copy of a non-mutated version of a disease-causing mutated gene. Examples of such enzymes include Cas9 (CRISPR technology), zinc finger nucleases, transcription activator-like effector nuclease mRNA (TALEN mRNA) and site-specific recombinases. As necessary, in some cases the mRNA would be used together with a “donor DNA” e.g. to insert the “correct” DNA sequence to correct a mutation, in other cases the mRNA may be used alone, e.g. for inactivating a gene. In preferred aspects, the method may be used to treat Huntingdon’s disease, cystic fibrosis and other inherited diseases.
Patentsøknaden inneholder hele 27 clames
Dette er en veldig gjennomført patentsøknad som baserer seg på omfattende testing
God helg !