• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Peptide derived from socs1 for use in chronic complications of diabetes, especially ocular, renal, nervous and vascular complications, as well as compositions containing it and isolated polynucleotides that encode it. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2552587A2
    申请号:ES201430796
    申请日:2014-05-28
    公开日:2015-11-30
    发明作者:Jesús EGIDO DE LOS RÍOS；Carmen GÓMEZ GUERRERO；Rafael Simó Canonge；Cristina Hernández Pascual
    申请人:Universidad Autonoma de Madrid；Fundacio Hospital Universitari Vall dHebron Institut de Recerca FIR VHIR；Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz；
    IPC主号:
    专利说明:

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    themselves, may be modified, preferably phosphorylated. According to a preferred embodiment, the phosphorylated amino acid or one of the phosphorylated amino acids will be a tyrosine (Y). Also, the SOCS1 protein according to the previous definitions may be linked to a region of cellular permeability, preferably to a lysine-palmitate group. According to a preferred embodiment, the cell permeability region is joined by the N-terminal end of the polypeptide, the cell permeability region being more preferably a lysine palmitate group.
    The identical variant in at least 85% includes the SOCS1 proteins of other mammals, such as Ratus Norvergicus, Gorilla, Oryctolagus cuniculus, Pan troglodytes, Pongo abelii, Cavia porcellus or Sus Scrofa.
    According to particular embodiments, the variant to the SOCS1 sequences of human or murine origin are identical in at least 90%, even more preferably in approximately 94%, to said sequences.
    All the preferred embodiments indicated for this first aspect of the invention are also applicable to the rest of aspects of the invention, detailed below.
    A further aspect of the invention is the use of an isolated polypeptide containing
    a) the sequence of SEQ ID NO 2 (DTHFRTFRSHADYRRI); or
    b) a variant to the sequence of a) that is at least 85% identical to SEQ ID NO 2, based on the identity of all the amino acids of said sequence;
    for the preparation of a medication for the prevention or treatment of chronic diabetes complications.
    According to another aspect of the invention, this refers to a composition comprising a therapeutically effective amount of a polypeptide according to any of the above definitions, and at least one pharmaceutically acceptable carrier or excipient, for use in prevention. or treatment of chronic complications of diabetes, according to the definition given above.
    In a preferred embodiment of the invention the composition is suitable or is intended for use in the prevention or treatment of eye disorders in diabetic patients, preferably diabetic retinopathy. It could also be used for other retinal diseases that occur with neurodegeneration, such as age-related macular degeneration, glaucoma and retinitis pigmentosa.
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    Thus according to a particular embodiment, the carrier or excipient is a pharmaceutically acceptable carrier or excipient suitable for ophthalmic administration.
    The compositions according to the present invention comprise at least one pharmaceutically acceptable carrier or excipient. The term "pharmaceutically acceptable carrier or excipient" refers to molecular substances or entities next to which the peptide of the invention is administered. Such vehicles or excipients will be suitable for the route of administration chosen, and will be apparent to a person skilled in the art depending on the route of administration. The vehicles may be sterile liquids, such as water or oils, including those derived from petroleum, animal, vegetable or synthetic origin, excipients, disintegrants, wetting agents,
    or diluents. Suitable vehicles and excipients are described for example in "Remington's Pharmaceutical Sciences" by E.W. Martin, which is incorporated by reference to the present application.
    The compositions according to the present invention can be administered by any known route, including oral, gastroenteric, parenteral, rectal, respiratory and topical, in particular ophthalmic. The compositions may also contain other suitable active ingredients or adjuvants that will be apparent to the person skilled in the art. Also the compositions could contain only a single polypeptide according to the invention.
    or two or more polypeptides according to the invention.
    In the case of the ophthalmic route, the vehicle or excipient must be suitable for this route of administration. The compositions in this case will be conveniently prepared, either as an aqueous solution or suspension, in a pharmaceutically acceptable ophthalmic base vehicle or solution. In addition to the active ingredient, in this case the polypeptide according to the invention may contain other adjuvants, such as antimicrobial agents, preservatives, chelating agents, tonicity regulating agents, pH regulating agents, including buffer solutions, viscous agents, etc.
    In the compositions according to the invention the peptide will be contained in a concentration range of 1-12 mg / mL. In the particular case of ocular administration, the peptide will be contained in a concentration of at least 5 mg / mL, in particular embodiments it will be contained in a concentration of at least 8 mg / mL, at least 9 mg / mL, at least 10 mg / mL, according to a preferred embodiment at a concentration of 10 mg / mL ± 5%, that is, 10 mg / mL ± 0.5 mg / mL. In the particular case of intraperitoneal administration, the peptide will be contained in a concentration of between 1 and 5 mg / mL, according to a particular embodiment it will be contained in a concentration of between 1 and 3 mg / mL, according to embodiments. preferred, at a concentration of 2 mg / mL ± 10% or ± 5%, that is, ± 0.2 mg / mL or ± 0.1 mg / mL.
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    "Kinase inhibitory region" of the SOCS1 protein, bound to a region of cellular permeability (lysine palmitate), in which tyrosine (Y) is phosphorylated. Throughout the examples, the peptide derivative formed by SEQ ID NO 1 and the lysine-palmitate group will be called miS1. In some cases it was conjugated with a fluorescent marker to allow its subsequent monitoring in tissues and cells. A mutated non-functional peptide (Mut) was also synthesized by replacing F (Phe) with A (Ala): SEQ ID NO 3, DTHARTARSHSDYRRI, Asp Thr His Ala Arg Thr Ala Arg Ser His Ser Asp Tyr Arg Arg Ile; also linked to the lysine palmitate cell permeability region, for use as a control of the experiments. The peptides were dissolved (<1% DMSO in saline) and sterilized by filtration.
    Animals:
    Two experimental models were used, namely an experimental model of type 2 diabetes (db / db mice) and another type 1 diabetes (streptozotocin injection in apoE mice). The mice were kept in standard-sized cages under controlled conditions of temperature (20 ° C) and humidity (60%), with 12-hour light / dark cycles and with access to food (standard diet) and ad libitum water. These studies have been carried out according to current Spanish legislation regarding the use, protection and care of experimental animals (Royal Decree 53/2013), following recommendations of the EEC (86/609 / EEC) and ARVO (Associationfor Research in Vision and Ophthalmology) and have been previously approved by the Ethical Committees of the two participating institutions (IIS-Fundación Jiménez Díaz / Autonomous University of Madrid and Institut de Recerca Hospital Universitari Vall d'Hebron).
    Treatment of neurodegeneration of the retina caused by diabetes by topical ocular treatment with a peptide derived from SOCS1
    Diabetic mice (db / db) of 8 weeks received the peptide eye drops miS1 (drops of 5 μL in each eye; 10 mg / mL; twice daily for 15 days; n = 4 mice). As controls, diabetic mice treated with the non-functional peptide Mut (n = 4), vehicle-treated and non-diabetic (db / +) were used. Weight and blood glucose (colorimetric assay) were monitored throughout the study period. On day 15, the animals were euthanized by cervical dislocation and the enucleated eyes were immediately frozen and 8mm dorsoventral sections were cut to analyze the morphology of the retina and other immunohistochemical analyzes. Glial activation was assessed by immunofluorescence of GFAP (Glial fibrillar acidic protein). The fixed sections were blocked (1% BSA and 10% goat serum in PBS, 2h at RT) and incubated with anti-GFAP antibodies (dilution 1: 500, 16h at 4 ° C) followed by a secondary antibody (goat anti-rabbit , conjugated with Alexa 488, dilution 1: 200). The samples were contrasted with Hoesch and
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    权利要求:
    Claims (1)
    [1]
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    同族专利:
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    ES2552587B1|2017-01-18|
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    WO2015181427A1|2015-12-03|
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    HUE041836T2|2019-05-28|
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    引用文献:
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    US20030175971A1|2001-12-28|2003-09-18|Geoffrey Lindeman|Differentiation and/or proliferation modulating agents and uses therefor|
    CA2558025A1|2004-03-04|2005-09-22|Vanderbilt University|Cell-penetrating socs polypeptides that inhibit cytokine-induced signaling|
    CN101437834B|2004-07-19|2012-06-06|贝勒医学院|Modulation of cytokine signaling regulators and applications for immunotherapy|
    EP1849474B1|2005-02-15|2016-09-07|Toagosei Co., Ltd.|Antimicrobial peptide and use thereof|
    EP1918297A4|2005-07-20|2010-03-10|Toagosei Co Ltd|Neuronal differentiation-inducing peptide and use thereof|
    WO2010151495A2|2009-06-26|2010-12-29|University Of Florida Research Foundation Inc.|Materials and methods for treating and preventing viral infections|
    US20110229525A1|2010-03-12|2011-09-22|Vanderbilt University|Modulation of cytokine signaling|
    CN102921007B|2011-08-09|2014-12-10|中国科学院上海生命科学研究院|Method and reagent used for controlling insulin resistance and diabetes mellitus|
    CN103173446A|2011-12-26|2013-06-26|吕成伟|Construction method of recombinant adeno-associated virus vector of targeting interference SOCS1 gene and application of construction method|
    ES2552587B1|2014-05-28|2017-01-18|Fundació Hospital Universitari Vall D'hebron-Institut De Recerca|PEPTIDE DERIVED FROM SOCS1 FOR USE IN CHRONIC COMPLICATIONS OF THE DIABETES|ES2552587B1|2014-05-28|2017-01-18|Fundació Hospital Universitari Vall D'hebron-Institut De Recerca|PEPTIDE DERIVED FROM SOCS1 FOR USE IN CHRONIC COMPLICATIONS OF THE DIABETES|
    CN105315377A|2015-12-07|2016-02-10|华东理工大学|TCS fusion protein with cell-penetrating peptide, plasmid, preparation method and application|
    CN106349347B|2016-10-25|2019-09-13|南通大学|A kind of micromolecule polypeptide and its encoding gene and application|
    法律状态:
    2016-12-28| PC2A| Transfer of patent|Owner name: FUNDACION INSTITUTO DE INVESTIGACION SANITARIA FUN Effective date: 20161221 |
    2017-01-18| FG2A| Definitive protection|Ref document number: 2552587 Country of ref document: ES Kind code of ref document: B1 Effective date: 20170118 |
    2021-10-04| FD2A| Announcement of lapse in spain|Effective date: 20211004 |
    优先权:
    申请号 | 申请日 | 专利标题
    ES201430796A|ES2552587B1|2014-05-28|2014-05-28|PEPTIDE DERIVED FROM SOCS1 FOR USE IN CHRONIC COMPLICATIONS OF THE DIABETES|ES201430796A| ES2552587B1|2014-05-28|2014-05-28|PEPTIDE DERIVED FROM SOCS1 FOR USE IN CHRONIC COMPLICATIONS OF THE DIABETES|
    CA2950348A| CA2950348A1|2014-05-28|2015-05-27|Socs1-derived peptide for use in chronic complications of diabetes|
    HUE15738128A| HUE041836T2|2014-05-28|2015-05-27|Socs1-derived peptide for use in chronic complications relating to diabetes|
    PL15738128T| PL3178485T3|2014-05-28|2015-05-27|Socs1-derived peptide for use in chronic complications relating to diabetes|
    BR112016027936A| BR112016027936A2|2014-05-28|2015-05-27|socs1-derived peptide for use in chronic diabetes complications|
    US15/314,395| US10532082B2|2014-05-28|2015-05-27|SOCS1-derived peptide for use in chronic complications of diabetes|
    PT15738128T| PT3178485T|2014-05-28|2015-05-27|Socs1-derived peptide for use in chronic complications relating to diabetes|
    MX2016015514A| MX369378B|2014-05-28|2015-05-27|Socs1-derived peptide for use in chronic complications relating to diabetes.|
    JP2017514978A| JP6681387B2|2014-05-28|2015-05-27|SOCS1-derived peptides for use in chronic complications of diabetes|
    ES15738128T| ES2715412T3|2014-05-28|2015-05-27|Peptide derived from SOCS1 for use in chronic complications of diabetes|
    TR2019/03509T| TR201903509T4|2014-05-28|2015-05-27|Socs1-derived peptide for use in chronic complications associated with diabetes.|
    EP15738128.6A| EP3178485B1|2014-05-28|2015-05-27|Socs1-derived peptide for use in chronic complications relating to diabetes|
    PCT/ES2015/070415| WO2015181427A1|2014-05-28|2015-05-27|Socs1-derived peptide for use in chronic complications relating to diabetes|
    CN201580040669.6A| CN107074922A|2014-05-28|2015-05-27|SOCS1 derived peptides for chronic complicating diseases of diabetes|
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