AR094317A1 - SHORT ACTION FACTOR VII POLIPEPTIDES - Google Patents

SHORT ACTION FACTOR VII POLIPEPTIDES

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Publication number
AR094317A1
AR094317A1 ARP130105071A ARP130105071A AR094317A1 AR 094317 A1 AR094317 A1 AR 094317A1 AR P130105071 A ARP130105071 A AR P130105071A AR P130105071 A ARP130105071 A AR P130105071A AR 094317 A1 AR094317 A1 AR 094317A1
Authority
AR
Argentina
Prior art keywords
hemorrhage
factor vii
mammal
moles
sequence
Prior art date
Application number
ARP130105071A
Other languages
Spanish (es)
Inventor
Bauzon Maxine
Hermiston Terry
Original Assignee
Bayer Healthcare Llc
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
Application filed by Bayer Healthcare Llc filed Critical Bayer Healthcare Llc
Publication of AR094317A1 publication Critical patent/AR094317A1/en

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Es deseable acortar la semivida para el tratamiento de hemorragias agudas y trastornos similares. La modificación de la sialilación y/o glucosilación del Factor VII y variantes del mismo produjeron péptidos útiles en el tratamiento de afecciones de hemorragia aguda. Reivindicación 1: Una composición de polipéptidos del Factor VII variantes, en la que los polipéptidos del Factor VII variantes comprenden una secuencia de aminoácidos que tiene al menos dos alteraciones de secuencia respecto a la secuencia de aminoácidos de SEC ID Nº 16, en la que al menos dos alteraciones de secuencia son (1) un residuo de glutamina sustituido por el residuo de prolina en la posición 10, y (2) un residuo de ácido glutámico sustituido por el residuo de lisina en la posición 32; y en la que la proporción entre los moles de ácido siálico conjugado por mol de glucano unido a N está dentro de un intervalo seleccionado del grupo que consiste en (1) de 0 a 5; (2) de 0 a 4; (3) de 0 a 3; (4) de 0 a 2; (5) de 0 a 1 y (6) de 0 a 0,5. Reivindicación 3: Un polipéptido del Factor VII variante aislado que comprende una secuencia de aminoácidos que tiene al menos dos alteraciones de secuencia respecto a la secuencia de aminoácidos de SEC ID Nº 16, en el que las al menos dos alteraciones de la secuencia son (1) un residuo de glutamina sustituido por el residuo de prolina en la posición 10 y (2) un residuo de ácido glutámico sustituido por el residuo de usina en la posición 32, en la que el polipéptido tiene una proporción entre los moles del ácido siálico conjugado y los moles del glucano unido a N entre 0 y 5,0. Reivindicación 29: Un procedimiento de tratamiento de un mamífero que tiene una enfermedad o trastorno en el que es deseable la formación de coágulos sanguíneos, comprendiendo dicho procedimiento administrar a un mamífero que lo necesite una cantidad eficaz de una composición que comprende los polipéptidos del Factor VII desialilado aislado, preparados mediante el procedimiento de la reivindicación 14, en el que la enfermedad o trastorno se selecciona del grupo que consiste en una hemorragia, hemorragia gastrointestinal, hemorragia incontrolada, hemorragia en un mamífero sometido a transplante o resección o cirugía, hemorragia varicosa, trombocitopenia, hemofilia, hemorragia intracraneal, aneurisma aórtico y sobre administración de un anticoagulante. Reivindicación 43: Una composición farmacéutica que comprende la composición de los polipéptidos del Factor VII variante de la reivindicación 1, y un excipiente farmacéuticamente aceptable. Reivindicación 49: Un procedimiento de tratamiento de un mamífero que tiene una enfermedad o trastorno en el que se desea que se formen coágulos sanguíneos, que comprende administrar a un mamífero que lo necesite una cantidad eficaz de un polipéptido del Factor VII que comprende la secuencia de aminoácidos de SEC ID Nº 16, en el que la proporción entre los moles del ácido siálico conjugado y los moles de Glucano unido a N es inferior a 0,05, en el que la enfermedad o trastorno es seleccionado del grupo que consiste en una hemorragia, hemorragia gastrointestinal, hemorragia incontrolada, hemorragia en un mamífero sometido a transplante o resección o cirugía, hemorragia por varices, trombocitopenia, hemofilia, hemorragia intracraneal, aneurisma aórtico y sobreadministración de un anticoagulante.It is desirable to shorten the half-life for the treatment of acute hemorrhages and similar disorders. Modification of the sialylation and / or glycosylation of Factor VII and variants thereof produced peptides useful in the treatment of acute bleeding conditions. Claim 1: A composition of variant Factor VII polypeptides, wherein the variant Factor VII polypeptides comprise an amino acid sequence having at least two sequence alterations with respect to the amino acid sequence of SEQ ID NO: 16, wherein minus two sequence alterations are (1) a glutamine residue substituted by the proline residue at position 10, and (2) a glutamic acid residue substituted by the lysine residue at position 32; and wherein the ratio between moles of conjugated sialic acid per mole of glucan attached to N is within a range selected from the group consisting of (1) from 0 to 5; (2) from 0 to 4; (3) from 0 to 3; (4) from 0 to 2; (5) from 0 to 1 and (6) from 0 to 0.5. Claim 3: An isolated variant Factor VII polypeptide comprising an amino acid sequence having at least two sequence alterations with respect to the amino acid sequence of SEQ ID NO: 16, wherein the at least two sequence alterations are (1 ) a glutamine residue substituted by the proline residue at position 10 and (2) a glutamic acid residue substituted by the usine residue at position 32, in which the polypeptide has a ratio between moles of conjugated sialic acid and the moles of glucan bound to N between 0 and 5.0. Claim 29: A method of treating a mammal having a disease or disorder in which blood clot formation is desirable, said method comprising administering to a mammal in need thereof an effective amount of a composition comprising Factor VII polypeptides. isolated desialylated, prepared by the method of claim 14, wherein the disease or disorder is selected from the group consisting of a hemorrhage, gastrointestinal bleeding, uncontrolled bleeding, hemorrhage in a mammal undergoing transplantation or resection or surgery, varicose hemorrhage, thrombocytopenia, hemophilia, intracranial hemorrhage, aortic aneurysm and administration of an anticoagulant. Claim 43: A pharmaceutical composition comprising the composition of the variant Factor VII polypeptides of claim 1, and a pharmaceutically acceptable excipient. Claim 49: A method of treating a mammal having a disease or disorder in which it is desired that blood clots form, comprising administering to an mammal in need thereof an effective amount of a Factor VII polypeptide comprising the sequence of amino acids of SEQ ID No. 16, in which the ratio between moles of conjugated sialic acid and moles of N-linked glucan is less than 0.05, in which the disease or disorder is selected from the group consisting of a hemorrhage , gastrointestinal hemorrhage, uncontrolled hemorrhage, hemorrhage in a mammal undergoing transplantation or resection or surgery, variceal hemorrhage, thrombocytopenia, hemophilia, intracranial hemorrhage, aortic aneurysm and over-administration of an anticoagulant.

ARP130105071A 2012-12-24 2013-12-27 SHORT ACTION FACTOR VII POLIPEPTIDES AR094317A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201261745674P 2012-12-24 2012-12-24

Publications (1)

Publication Number Publication Date
AR094317A1 true AR094317A1 (en) 2015-07-29

Family

ID=56117356

Family Applications (4)

Application Number Title Priority Date Filing Date
ARP130105071A AR094317A1 (en) 2012-12-24 2013-12-27 SHORT ACTION FACTOR VII POLIPEPTIDES
ARP200101073A AR118704A2 (en) 2012-12-24 2020-04-16 FACTOR VII POLIPEPTIDE TO TREAT DISEASES
ARP200101072A AR118703A2 (en) 2012-12-24 2020-04-16 FACTOR VII POLIPEPTIDE TO TREAT A DISEASE
ARP200101074A AR118705A2 (en) 2012-12-24 2020-04-16 FACTOR VII POLIPEPTIDE TO TREAT DISEASES, METHOD FOR PREPARING IT AND COMPOSITION CONTAINING IT

Family Applications After (3)

Application Number Title Priority Date Filing Date
ARP200101073A AR118704A2 (en) 2012-12-24 2020-04-16 FACTOR VII POLIPEPTIDE TO TREAT DISEASES
ARP200101072A AR118703A2 (en) 2012-12-24 2020-04-16 FACTOR VII POLIPEPTIDE TO TREAT A DISEASE
ARP200101074A AR118705A2 (en) 2012-12-24 2020-04-16 FACTOR VII POLIPEPTIDE TO TREAT DISEASES, METHOD FOR PREPARING IT AND COMPOSITION CONTAINING IT

Country Status (1)

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AR (4) AR094317A1 (en)

Also Published As

Publication number Publication date
AR118703A2 (en) 2021-10-27
AR118704A2 (en) 2021-10-27
AR118705A2 (en) 2021-10-27

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