AR108969A1 - DERIVED FROM GLUCAGÓN, A CONJUGATE OF HIMSELF, AND A COMPOSITION THAT INCLUDES THE SAME, AND A THERAPEUTIC USE OF THE SAME - Google Patents

DERIVED FROM GLUCAGÓN, A CONJUGATE OF HIMSELF, AND A COMPOSITION THAT INCLUDES THE SAME, AND A THERAPEUTIC USE OF THE SAME

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Publication number
AR108969A1
AR108969A1 ARP170101804A ARP170101804A AR108969A1 AR 108969 A1 AR108969 A1 AR 108969A1 AR P170101804 A ARP170101804 A AR P170101804A AR P170101804 A ARP170101804 A AR P170101804A AR 108969 A1 AR108969 A1 AR 108969A1
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AR
Argentina
Prior art keywords
cysteine
absent
lysine
valine
glutamic acid
Prior art date
Application number
ARP170101804A
Other languages
Spanish (es)
Inventor
Sung Youb Jung
In Young Choi
Young Jin Park
Jung Kuk Kim
Original Assignee
Hanmi Pharm Ind Co Ltd
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Publication date
Application filed by Hanmi Pharm Ind Co Ltd filed Critical Hanmi Pharm Ind Co Ltd
Publication of AR108969A1 publication Critical patent/AR108969A1/en

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

Abstract

Reivindicación 1: Una composición farmacéutica para prevenir o tratar hiperinsulinismo congénito que comprende la secuencia de aminoácidos de la fórmula general (1): X¹-X²-QGTF-X⁷-SD-X¹⁰-S-X¹²-X¹³-X¹⁴-X¹⁵-X¹⁶-X¹⁷-X¹⁸-X¹⁹-X²⁰-X²¹-F-X²³-X²⁴-W-L-X²⁷-X²⁸-X²⁹-X³⁰ (fórmula general (1), SEQ ID Nº 45) donde, de la fórmula general (1), X¹ es histidina (H), desamino-histidilo, N-dimetil-histidilo, b-hidroxi imidazopropionilo, 4-imidazoacetilo, b-carboxi imidazopropionilo, triptofano (W), o tirosina (Y), o está ausente; X² es ácido a-metil-glutámico, ácido aminoisobutírico (Aib), D-alanina, glicina (G), Sar (N-metilglicina), serina (S), o D-serina; X⁷ es treonina (T), valina (V), o cisteína (C); X¹⁰ es tirosina (Y) o cisteína (C); X¹² es lisina (K) o cisteína (C); X¹³ es tirosina (Y) o cisteína (C); X¹⁴ es leucina (L) o cisteína (C); X¹⁵ es ácido aspártico (D), ácido glutámico (E), o cisteína (C); X¹⁶ es ácido glutámico (E), ácido aspártico (D), serina (S), ácido a-metil-glutámico, o cisteína (C), o está ausente; X¹⁷ es ácido aspártico (D), glutamina (Q), ácido glutámico (E), lisina (K) arginina (R), serina (S), cisteína (C), o valina (V), o está ausente; X¹⁸ es alanina (A), ácido aspártico (D), ácido glutámico (E), arginina (R) valina (V), o cisteína (C), o está ausente; X¹⁹ es alanina (A), arginina (R), serina (S), valina (V), o cisteína (C), o está ausente; X²⁰ es lisina (K), histidina (H), glutamina (Q), ácido aspártico (D), arginina (R), ácido a-metil-glutámico, o cisteína (C), o está ausente; X²¹ es ácido aspártico (D), ácido glutámico (E), leucina (L), valina (V), o cisteína (C), o está ausente; X²³ es isoleucina (I), valina (V), o arginina (R), o está ausente; X²⁴ es valina (V), arginina (R), alanina (A), cisteína (C), ácido glutámico (E), lisina (K), glutamina (Q), ácido a-metil-glutámico, o leucina (L), o está ausente; X²⁷ es isoleucina (I), valina (V), alanina (A), lisina (K), metionina (M), glutamina (Q), o arginina (R), o está ausente; X²⁸ es glutamina (Q), lisina (K), asparagina (N), o arginina (R), o está ausente; X²⁹ es lisina (K), alanina (A), glicina (G), o treonina (T), o está ausente; y X³⁰ es cisteína (C), o está ausente; con la condición de que cuando la secuencia de aminoácidos de fórmula general (1) es idéntica a la SEQ ID Nº 1, se excluye. Reivindicación 35: Un péptido aislado que comprende la secuencia de aminoácidos de la fórmula general (2): Y-Aib-QGTF-X⁷-SD-X¹⁰-S-X¹²-Y-L-X¹⁵-X¹⁶-X¹⁷-R-A-X²⁰-X²¹-F-V-X²⁴-W-L-M-N-T-X³⁰ (fórmula general (2), SEQ ID Nº 46) donde, de la fórmula general (2), X⁷ es treonina (T), valina (V), o cisteína (C); X¹⁰ es tirosina (Y) o cisteína (C); X¹² es lisina (K) o cisteína (C); X¹⁵ es ácido aspártico (D) o cisteína (C); X¹⁶ es ácido glutámico (E) o serina (S); X¹⁷ es lisina (K) o arginina (R); X²⁰ es glutamina (Q) o lisina (K); X²¹ es ácido aspártico (D) o ácido glutámico (E); X²⁴ es valina (V) o glutamina (Q); y X³⁰ es cisteína (C) o está ausente, con la condición de que los péptidos correspondientes a las SEQ ID Nº 19, 33, 49, y 50 se excluyen de los péptidos aislados que comprenden la secuencia de aminoácidos de la fórmula general (2). Reivindicación 40: Un conjugado aislado que comprende un resto peptídico y un resto de material biocompatible que se liga al resto de péptido, donde el resto de péptido es la misma secuencia que la secuencia de aminoácidos de la fórmula general (2) o una secuencia que incluye la misma: Y-Aib-QGTF-X⁷-SD-X¹⁰-S-X¹²-Y-L-X¹⁵-X¹⁶-X¹⁷-R-A-X²⁰-X²¹-F-V-X²⁴-W-L-M-N-T-X³⁰ (fórmula general (2), SEQ ID Nº 46) donde, de la fórmula general (2), X⁷ es treonina (T), valina (V), o cisteína (C); X¹⁰ es tirosina (Y) o cisteína (C); X¹² es lisina (K) o cisteína (C); X¹⁵ es ácido aspártico (D) o cisteína (C); X¹⁶ es ácido glutámico (E) o serina (S); X¹⁷ es lisina (K) o arginina (R); X²⁰ es glutamina (Q) o lisina (K); X²¹ es ácido aspártico (D) o ácido glutámico (E); X²⁴ es valina (V) o glutamina (Q); y X³⁰ es cisteína (C) o está ausente. Reivindicación 47: Una composición farmacéutica para prevenir o tratar hipoglucemia, que comprende: (i) el péptido aislado de acuerdo con cualquiera de las reivindicaciones 35 a 39 o el conjugado aislado de acuerdo con cualquiera de las reivindicaciones 40 a 46; y (ii) un excipiente farmacéuticamente aceptable. Reivindicación 55: Un método para prevenir o tratar hipoglucemia que comprende administrar el péptido aislado de acuerdo con cualquiera de las reivindicaciones 35 a 39 o el conjugado aislado de acuerdo con cualquiera de las reivindicaciones 40 a 46 a un sujeto que lo necesita.Claim 1: A pharmaceutical composition for preventing or treating congenital hyperinsulinism comprising the amino acid sequence of the general formula (1): X¹-X²-QGTF-X⁷-SD-X¹⁰-S-X¹²-X¹³-X¹⁴-X¹⁵-X¹⁶- X¹⁷-X¹⁸-X¹⁹-X²⁰-X²¹-F-X²³-X²⁴-WL-X²⁷-X²⁸-X²⁹-X³⁰ (general formula (1), SEQ ID No. 45) where, of the general formula (1), X¹ is histidine (H), deamino-histidyl, N-dimethyl-histidyl, b-hydroxy imidazopropionyl, 4-imidazoacetyl, b-carboxy imidazopropionyl, tryptophan (W), or tyrosine (Y), or is absent; X² is a-methyl-glutamic acid, aminoisobutyric acid (Aib), D-alanine, glycine (G), Sar (N-methylglycine), serine (S), or D-serine; X⁷ is threonine (T), valine (V), or cysteine (C); X¹⁰ is tyrosine (Y) or cysteine (C); X¹² is lysine (K) or cysteine (C); X¹³ is tyrosine (Y) or cysteine (C); X¹⁴ is leucine (L) or cysteine (C); X¹⁵ is aspartic acid (D), glutamic acid (E), or cysteine (C); X¹⁶ is glutamic acid (E), aspartic acid (D), serine (S), a-methyl-glutamic acid, or cysteine (C), or is absent; X¹⁷ is aspartic acid (D), glutamine (Q), glutamic acid (E), lysine (K) arginine (R), serine (S), cysteine (C), or valine (V), or is absent; X¹⁸ is alanine (A), aspartic acid (D), glutamic acid (E), arginine (R) valine (V), or cysteine (C), or is absent; X¹⁹ is alanine (A), arginine (R), serine (S), valine (V), or cysteine (C), or is absent; X²⁰ is lysine (K), histidine (H), glutamine (Q), aspartic acid (D), arginine (R), a-methyl-glutamic acid, or cysteine (C), or is absent; X²¹ is aspartic acid (D), glutamic acid (E), leucine (L), valine (V), or cysteine (C), or is absent; X²³ is isoleucine (I), valine (V), or arginine (R), or is absent; X²⁴ is valine (V), arginine (R), alanine (A), cysteine (C), glutamic acid (E), lysine (K), glutamine (Q), a-methyl-glutamic acid, or leucine (L) , or is absent; X²⁷ is isoleucine (I), valine (V), alanine (A), lysine (K), methionine (M), glutamine (Q), or arginine (R), or is absent; X²⁸ is glutamine (Q), lysine (K), asparagine (N), or arginine (R), or is absent; X²⁹ is lysine (K), alanine (A), glycine (G), or threonine (T), or is absent; and X³⁰ is cysteine (C), or is absent; with the proviso that when the amino acid sequence of general formula (1) is identical to SEQ ID No. 1, it is excluded. Claim 35: An isolated peptide comprising the amino acid sequence of the general formula (2): Y-Aib-QGTF-X⁷-SD-X¹⁰-S-X¹²-YL-X¹⁵-X¹⁶-X¹⁷-RA-X²⁰-X²¹- FV-X²⁴-WLMNT-X³⁰ (general formula (2), SEQ ID No. 46) where, of the general formula (2), X⁷ is threonine (T), valine (V), or cysteine (C); X¹⁰ is tyrosine (Y) or cysteine (C); X¹² is lysine (K) or cysteine (C); X¹⁵ is aspartic acid (D) or cysteine (C); X¹⁶ is glutamic acid (E) or serine (S); X¹⁷ is lysine (K) or arginine (R); X²⁰ is glutamine (Q) or lysine (K); X²¹ is aspartic acid (D) or glutamic acid (E); X²⁴ is valine (V) or glutamine (Q); and X³⁰ is cysteine (C) or is absent, with the proviso that the peptides corresponding to SEQ ID Nos. 19, 33, 49, and 50 are excluded from isolated peptides comprising the amino acid sequence of the general formula (2 ). Claim 40: An isolated conjugate comprising a peptide moiety and a biocompatible material moiety that binds to the peptide moiety, wherein the peptide moiety is the same sequence as the amino acid sequence of the general formula (2) or a sequence that It includes: Y-Aib-QGTF-X⁷-SD-X¹⁰-S-X¹²-YL-X¹⁵-X¹⁶-X¹⁷-RA-X²⁰-X²¹-FV-X²⁴-WLMNT-X³⁰ (general formula (2), SEQ ID No. 46) where, of the general formula (2), X⁷ is threonine (T), valine (V), or cysteine (C); X¹⁰ is tyrosine (Y) or cysteine (C); X¹² is lysine (K) or cysteine (C); X¹⁵ is aspartic acid (D) or cysteine (C); X¹⁶ is glutamic acid (E) or serine (S); X¹⁷ is lysine (K) or arginine (R); X²⁰ is glutamine (Q) or lysine (K); X²¹ is aspartic acid (D) or glutamic acid (E); X²⁴ is valine (V) or glutamine (Q); and X³⁰ is cysteine (C) or is absent. Claim 47: A pharmaceutical composition for preventing or treating hypoglycemia, comprising: (i) the isolated peptide according to any one of claims 35 to 39 or the isolated conjugate according to any one of claims 40 to 46; and (ii) a pharmaceutically acceptable excipient. Claim 55: A method of preventing or treating hypoglycemia comprising administering the isolated peptide according to any of claims 35 to 39 or the isolated conjugate according to any of claims 40 to 46 to a subject in need thereof.

ARP170101804A 2016-06-29 2017-06-29 DERIVED FROM GLUCAGÓN, A CONJUGATE OF HIMSELF, AND A COMPOSITION THAT INCLUDES THE SAME, AND A THERAPEUTIC USE OF THE SAME AR108969A1 (en)

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KR20160081995 2016-06-29

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AR108969A1 true AR108969A1 (en) 2018-10-17

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MA (1) MA44558B1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023001186A1 (en) * 2021-07-20 2023-01-26 派格生物医药(苏州)股份有限公司 Polypeptide conjugate and application thereof in preparation of drug for treating diseases related to glucose metabolism

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023001186A1 (en) * 2021-07-20 2023-01-26 派格生物医药(苏州)股份有限公司 Polypeptide conjugate and application thereof in preparation of drug for treating diseases related to glucose metabolism

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Publication number Publication date
MA44558A1 (en) 2020-02-28
MA44558B1 (en) 2022-04-29

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