AR086969A1 - Conjugado que comprende oxontomodulina y un fragmento de inmunoglobulina, y su uso - Google Patents
Conjugado que comprende oxontomodulina y un fragmento de inmunoglobulina, y su usoInfo
- Publication number
- AR086969A1 AR086969A1 ARP120102154A ARP120102154A AR086969A1 AR 086969 A1 AR086969 A1 AR 086969A1 AR P120102154 A ARP120102154 A AR P120102154A AR P120102154 A ARP120102154 A AR P120102154A AR 086969 A1 AR086969 A1 AR 086969A1
- Authority
- AR
- Argentina
- Prior art keywords
- suppressed
- alanine
- serine
- seq
- glutamine
- Prior art date
Links
- 108060003951 Immunoglobulin Proteins 0.000 title abstract 4
- 102000018358 immunoglobulin Human genes 0.000 title abstract 4
- 239000012634 fragment Substances 0.000 title 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical group C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 abstract 8
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- 235000004400 serine Nutrition 0.000 abstract 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 abstract 6
- 239000004475 Arginine Chemical group 0.000 abstract 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 abstract 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 abstract 6
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical group NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 abstract 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 abstract 6
- 239000004472 Lysine Substances 0.000 abstract 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Chemical group OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 abstract 6
- 235000009697 arginine Nutrition 0.000 abstract 6
- 235000013922 glutamic acid Nutrition 0.000 abstract 6
- 239000004220 glutamic acid Substances 0.000 abstract 6
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Chemical group OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 abstract 6
- 235000004554 glutamine Nutrition 0.000 abstract 6
- 235000018977 lysine Nutrition 0.000 abstract 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 abstract 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical group OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 abstract 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 abstract 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 abstract 4
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- 235000005772 leucine Nutrition 0.000 abstract 4
- 239000004474 valine Substances 0.000 abstract 4
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical group CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 abstract 3
- QHSCIWIRXWFIGH-UHFFFAOYSA-N 2-amino-2-methylpentanedioic acid Chemical compound OC(=O)C(N)(C)CCC(O)=O QHSCIWIRXWFIGH-UHFFFAOYSA-N 0.000 abstract 3
- 239000004471 Glycine Substances 0.000 abstract 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 abstract 3
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- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 abstract 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 abstract 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 abstract 2
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- -1 deamino-histidyl Chemical group 0.000 abstract 2
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- 229930182817 methionine Natural products 0.000 abstract 2
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- 235000020824 obesity Nutrition 0.000 abstract 2
- 125000001151 peptidyl group Chemical group 0.000 abstract 2
- 229920000642 polymer Polymers 0.000 abstract 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 abstract 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 abstract 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 abstract 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 abstract 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 abstract 1
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- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 abstract 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 abstract 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 abstract 1
- 108010077895 Sarcosine Proteins 0.000 abstract 1
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- 239000004473 Threonine Substances 0.000 abstract 1
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- 230000004913 activation Effects 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 abstract 1
- 229940024606 amino acid Drugs 0.000 abstract 1
- 235000009582 asparagine Nutrition 0.000 abstract 1
- 229960001230 asparagine Drugs 0.000 abstract 1
- 230000037406 food intake Effects 0.000 abstract 1
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- 230000030136 gastric emptying Effects 0.000 abstract 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 abstract 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 abstract 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 abstract 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 abstract 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 abstract 1
- 230000004130 lipolysis Effects 0.000 abstract 1
- 230000007774 longterm Effects 0.000 abstract 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 abstract 1
Classifications
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- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
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- C—CHEMISTRY; METALLURGY
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Una composición farmacéutica para la prevención o el tratamiento de obesidad que comprende a los conjugados. El conjugado que comprende oxintomodulina y la región Fc de inmunoglobulina de la presente reduce la ingesta de alimentos, suprime el vaciado gástrico, y facilita la lipólisis sin efectos secundarios, a diferencia de la oxintomodulina nativa, y también presenta excelentes efectos de activación del receptor y sostenibilidad a largo plazo, en comparación con la oxintomodulina nativa. Por lo tanto, se puede utilizar ampliamente en el tratamiento de obesidad con seguridad y eficacia.Reivindicación 1: Un conjugado, caracterizado porque comprende oxintomodulina, una región Fc de inmunoglobulina y un polímero no peptidílico, en donde el conjugado se puede obtener por unión covalente de la oxintomodulina a la región Fc de inmunoglobulina a través de un polímero no peptidílico. Reivindicación 4: El conjugado de acuerdo con la reivindicación 3, caracterizado porque el derivado de la oxintomodulina comprende la secuencia de aminoácidos de la fórmula (1): R1-X1-X2-GTFTSD-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-X22-X23-X24-R2 (1) donde R1 es histidina, desamino-histidilo, dimetil-histidilo (N-dimetilhistidilo), b-hidroxiimidazopropionilo, 4-imidazoacetilo, b-carboxi imidazopropionilo o tirosina; X1 es Aib (ácido aminoisobutírico), d-alanina, glicina, Sar (N-metilglicina), serina o d-serina; X2 es ácido glutámico o glutamina; X3 es leucina o tirosina; X4 es serina o alanina; X5 es lisina o arginina; X6 es glutamina o tirosina; X7 es leucina o metionina; X8 es ácido aspártico o ácido glutámico; X9 es ácido glutámico, serina o ácido a-metilglutámico, o bien ha sido suprimido; X10 es glutamina, ácido glutámico, lisina, arginina o serina, o bien ha sido suprimido; X11 es alanina, arginina o valina, o bien ha sido suprimido; X12 es alanina, arginina, serina o valina, o bien ha sido suprimido; X13 es lisina, glutamina, arginina o ácido a-metilglutámico, o bien ha sido suprimido; X14 es ácido aspártico, ácido glutámico o leucina, o bien ha sido suprimido; X15 es fenilalanina o ha sido suprimido; X16 es isoleucina o valina, o bien ha sido suprimido; X17 es alanina, cisteína, ácido glutámico, lisina, glutamina o ácido a-metilglutámico, o bien ha sido suprimido; X18 es triptofano o ha sido suprimido; X19 es alanina, isoleucina, leucina, serina o valina, o bien ha sido suprimido; X20 es alanina, lisina, metionina, glutamina o arginina, o bien ha sido suprimido; X21 es asparragina o ha sido suprimido; X22 es alanina, glicina o treonina, o bien ha sido suprimido; X23 es cisteína o lisina, o bien ha sido suprimido; X24 es un péptido que comprende entre 2 y 10 aminoácidos, que en particular consiste en combinaciones de alanina, glicina y serina, o bien ha sido suprimido; y R2 es KRNRNNIA (SEQ ID Nº 35), GPSSGAPPPS (SEQ ID Nº 36), GPSSGAPPPSK (SEQ ID Nº 37), HSQGTFTSDYSKYLD (SEQ ID Nº 38), HSQGTFTSDYSRYLDK (SEQ ID Nº 39) o HGEGTFTSDLSKQMEEEAVK (SEQ ID Nº 40), o bien ha sido suprimido (es decir, se lo excluye si la secuencia de aminoácidos de fórmula (1) es idéntica a SEQ ID Nº 1).
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20110058852 | 2011-06-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR086969A1 true AR086969A1 (es) | 2014-02-05 |
Family
ID=47357296
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP120102154A AR086969A1 (es) | 2011-06-17 | 2012-06-15 | Conjugado que comprende oxontomodulina y un fragmento de inmunoglobulina, y su uso |
| ARP220101329A AR125914A2 (es) | 2011-06-17 | 2022-05-19 | Conjugado que comprende oxintomodulina y un fragmento de inmunoglobulina y su uso |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP220101329A AR125914A2 (es) | 2011-06-17 | 2022-05-19 | Conjugado que comprende oxintomodulina y un fragmento de inmunoglobulina y su uso |
Country Status (33)
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| EP (2) | EP2721062B1 (es) |
| JP (2) | JP6038905B2 (es) |
| KR (2) | KR101577734B1 (es) |
| CN (2) | CN109306015B (es) |
| AR (2) | AR086969A1 (es) |
| AU (3) | AU2012270366C1 (es) |
| BR (1) | BR112013032375B1 (es) |
| CA (2) | CA3080189C (es) |
| CL (1) | CL2013003619A1 (es) |
| CY (1) | CY1121255T1 (es) |
| DK (2) | DK2721062T3 (es) |
| ES (2) | ES2710356T3 (es) |
| HR (1) | HRP20190265T1 (es) |
| HU (1) | HUE042585T2 (es) |
| IL (4) | IL229759A (es) |
| LT (1) | LT2721062T (es) |
| MX (2) | MX381780B (es) |
| MY (1) | MY164680A (es) |
| PE (3) | PE20181268A1 (es) |
| PH (2) | PH12018501119B1 (es) |
| PL (1) | PL2721062T3 (es) |
| PT (1) | PT2721062T (es) |
| RS (1) | RS58606B1 (es) |
| RU (2) | RU2733544C2 (es) |
| SG (2) | SG195275A1 (es) |
| SI (1) | SI2721062T1 (es) |
| SM (1) | SMT201900078T1 (es) |
| TR (1) | TR201901402T4 (es) |
| TW (2) | TWI601744B (es) |
| UA (2) | UA114709C2 (es) |
| WO (1) | WO2012173422A1 (es) |
| ZA (1) | ZA201309013B (es) |
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