SU1664845A1 - Method for obtaining peptides - Google Patents
Method for obtaining peptides Download PDFInfo
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- SU1664845A1 SU1664845A1 SU867774327A SU7774327A SU1664845A1 SU 1664845 A1 SU1664845 A1 SU 1664845A1 SU 867774327 A SU867774327 A SU 867774327A SU 7774327 A SU7774327 A SU 7774327A SU 1664845 A1 SU1664845 A1 SU 1664845A1
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- USSR - Soviet Union
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- ala
- nitroanilide
- leu
- asp
- yield
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 10
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 8
- 238000000034 method Methods 0.000 title claims description 11
- 102000005741 Metalloproteases Human genes 0.000 claims abstract description 9
- 108010006035 Metalloproteases Proteins 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 238000001042 affinity chromatography Methods 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 5
- 241000193755 Bacillus cereus Species 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000012531 culture fluid Substances 0.000 claims description 3
- 229960003438 aspartame Drugs 0.000 abstract description 8
- 239000000605 aspartame Substances 0.000 abstract description 8
- YSCNREZXFSZAQO-ROUUACIJSA-N (3s)-4-[[(2s)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxo-3-(phenylmethoxycarbonylamino)butanoic acid Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H](CC(O)=O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 YSCNREZXFSZAQO-ROUUACIJSA-N 0.000 abstract description 3
- 108010011485 Aspartame Proteins 0.000 abstract description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 abstract description 3
- 235000010357 aspartame Nutrition 0.000 abstract description 3
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241001660259 Cereus <cactus> Species 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- XYXYXSKSTZAEJW-VIFPVBQESA-N (2s)-2-(phenylmethoxycarbonylamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 XYXYXSKSTZAEJW-VIFPVBQESA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000193389 Bacillus thermoproteolyticus Species 0.000 description 1
- 102000010750 Metalloproteins Human genes 0.000 description 1
- 108010063312 Metalloproteins Proteins 0.000 description 1
- 241000194105 Paenibacillus polymyxa Species 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Enzymes And Modification Thereof (AREA)
Abstract
Изобретение относитс к способу получени пептидов, особенно Z-ALA-ALA-LEN-P-нитроанилида и Z-L-ASP-L-PHEOME (аспартама) в присутствии металлопротеиназ. Цель изобретени - повышение выхода трипептидов (Z-аспартама). Способ заключаетс в св зывании Z-ALA-ALA с LEN-P-нитроанилидом и Z-L-ASP с L-PHEOME-HCL в присутствии протеиназы из BACILLUS CEREUS ZIMET 10700. МЕТАЛЛОПРОТЕИНАЗУ ИСПОЛЬЗУЮТ В ВИДЕ ФИЛЬТРАТА КУЛЬТУРАЛЬНОЙ ЖИДКОСТИ ИЛИ ОЧИЩЕННОГО АФИННОЙ ХРОМАТОГРАФИЕЙ С БАЦИТРАЦИН-СИЛОХРОМОМ.This invention relates to a method for producing peptides, especially Z-ALA-ALA-LEN-P-nitroanilide and Z-L-ASP-L-PHEOME (aspartame) in the presence of metalloproteinases. The purpose of the invention is to increase the yield of tripeptides (Z-aspartame). A way to connect Z-ALA-ALA .
Description
1 (89) DD 257174 (48) 08.06.881 (89) DD 257174 (48) 08.06.88
(21)7774327/13(21) 7774327/13
(22)03.11.86(22) 11/03/86
(31JWPC 12 Р/284889(31JWPC 12 P / 284889
(32)20.12.85(32) 12.20.85
(33) DD(33) DD
(46)23.07.91. Бюл. №27(46) 07.23.91. Bul №27
(71)Научный центр по биотехнологии (DD), Всесоюзный научно-исследовательский институт генетики и селекции промышленных микроорганизмов(51)5(71) Biotechnology Research Center (DD), All-Union Scientific Research Institute of Genetics and Selection of Industrial Microorganisms (51) 5
(72)Ульрих Корн (DD), А.Л. Остерман, В.М. Степанов, Т.Л. Воюшина. Л.А. Люблинска (SU), Райнер Грунов (DD)(72) Ulrich Korn (DD), A.L. Osterman, V.M. Stepanov, T.L. Voyushin L.A. Lublin (SU), Rainer Grunov (DD)
(53) 668.392 (088.8)(53) 668.392 (088.8)
(57) СПОСОБ ПОЛУЧЕНИЯ ПЕПТИДОВ (57) Изобретение относитс к способу получени пептидов, особенно Z-Ala-A a-Leu-p- нитроанилида и Z-L-Asp-L-Phe OMe (аспартама) в присутствии металлопротеи- наз. Цель изобретени - повышение выхода трипептидов (Z-аспартама). Способ заключаетс в св зывании Z-Ala-Aia с Leu-p-нитро- анилидом и Z-L-Asp с L-PheOMe-HCI в присутствии протеиназы из Bacillus cereus ZIMET 10700 Металлопротеиназуиспользуют в виде фильтрата культуральной жидкости или очищенного афинной хроматографией с бацитрацин-силохромом. 1 з.п ф-лы(57) METHOD FOR OBTAINING PEPTIDES (57) The invention relates to a method for producing peptides, especially Z-Ala-A a-Leu-p-nitroanilide and Z-L-Asp-L-Phe OMe (aspartame) in the presence of metalloprotein. The purpose of the invention is to increase the yield of tripeptides (Z-aspartame). The method involves binding Z-Ala-Aia with Leu-p-nitro-anilide and ZL-Asp with L-PheOMe-HCI in the presence of a proteinase from Bacillus cereus ZIMET 10700 Metalloproteinase used in the form of a filtrate of culture liquid or purified by bacinitacin-silochrom affinity chromatography . 1 z p f-ly
Изобретение относитс к способу по получению пептидов, особенно Z-Ala-Ala- Leu-p-нитроанилида и Z-L-Asp-L-PheoMe (аспартама), в присутствии металлопротеи- наз.The invention relates to a process for the preparation of peptides, especially Z-Ala-Ala-Leu-p-nitroanilide and Z-L-Asp-L-PheoMe (aspartame), in the presence of metalloproteinis.
Из обзора ISOWA, V, Vu ki Case Kagaku Kycka aishi, 36, 1978, 195-20 известен способ получени пептидов с использованием протеиназ в качестве катализаторов. При этом используютс серинпротеи- назы и металлопротеиназы разного биологического происхождени из Bacillus polymyxa, Bacillus subtilis, Bacillus thermoproteolyticus и др.From the review of ISOWA, V, Vu ki, Case Kagaku Kycka aishi, 36, 1978, 195-20, there is known a method for producing peptides using proteinases as catalysts. In this case, serine proteinases and metalloproteinases of different biological origin from Bacillus polymyxa, Bacillus subtilis, Bacillus thermoproteolyticus, etc. are used.
Недостатком данного способа вл етс то, что эти ферменты требуют глубокой очистки .The disadvantage of this method is that these enzymes require deep cleaning.
Из описани патента ФРГ № 3203292, кл. С 12 Р 21/00, опублик 1985 известен способ получени пептидов путем св зывани Z-Ala-Ala с Leu-p-нитроанилидом и Z-L (ЛFrom the description of the patent of Germany No. 3203292, cl. C 12 P 21/00, published 1985, a method for producing peptides by binding Z-Ala-Ala to Leu-p-nitroanilide and Z-L (L
СWITH
Asp с Zthe-оме-НС в присутствии металлопротеиназы .Asp with Zthe-ome-NS in the presence of metalloproteinase.
Недостатком этого способа вл етс .о, что при этом образуетс незначительное количество трипептидовThe disadvantage of this method is that it produces a small amount of tripeptides.
Целью изобретени вл етс повышение выхода целевых продуктовThe aim of the invention is to increase the yield of target products.
Металлопротеиназа из В.cereus ZIMET 10700 примен етс дл получени пептида Z-Ala-Ala-Leu-р-нитроанилида или пептида Z-L-Asp-L-PheOMe, при этом установлено, что этот ферментможноиспользоватьтакже в виде фильтрата культуральной жидкости или очищенного аффинной хроматографией с бацитрацин-силохромомThe metalloproteinase from B. cereus ZIMET 10700 is used to prepare the peptide Z-Ala-Ala-Leu-p-nitroanilide or the peptide ZL-Asp-L-PheOMe, and it has been established that bacitracin-silochrome
Эффективность синтеза выше, если примен етс очищенный фермент. Действенным методом очистки дл металлопротеиназы из Вас. cereus ZIMET 10700 вл етс аффинна хроматографи с бацитрацин-силохромом В результате очистки получаютThe efficiency of the synthesis is higher if the purified enzyme is used. An effective purification method for metalloproteinases from you. cereus ZIMET 10700 is a bacitracin-silochrome affinity chromatography. As a result of purification,
оabout
4four
оэoh
4 СЛ4 SL
фермент, почти свободный от углеводов и чужих протеинов. Этот фермент позвол ет повысить скорость реакции и выход конечного продукта.an enzyme almost free of carbohydrates and foreign proteins. This enzyme improves the reaction rate and the yield of the final product.
Пример 1. 74 мг Z-A a-Ala и 62 мг Leu-p-нитроанилида раствор ют в 250 мкл диметилформамида и смешивают с 500 мклExample 1. 74 mg of Z-A a-Ala and 62 mg of Leu-p-nitroanilide are dissolved in 250 µl of dimethylformamide and mixed with 500 µl
50мМ трис-HCI, рН 7,5, с 1 мм Са-ацетата, при 35°С и добавл ют 180 мкл фильтрата культуральной жидкости из Вас. cereus ZIMET 10700, содержащего 140 мкг фермента . Концентраци субстратов при этом составл ет по 200 мкмоль. При перемешивании в течение 25 ч при 35°С получено50 mM Tris-HCl, pH 7.5, with 1 mm Ca-acetate, at 35 ° C and 180 µl of the culture fluid filtrate from you is added. cereus ZIMET 10700, containing 140 μg of enzyme. The concentration of the substrates is 200 µmol each. With stirring for 25 h at 35 ° C obtained
51% продукта. Качественный анализ конеч- ного продукта провод т тонкослойной хроматографией на силикагельных пластинках51% of the product. Qualitative analysis of the final product is carried out by thin layer chromatography on silica gel plates.
в системе н-бутанол : пиридин : уксусна кислота : вода в соотношении 10:15:3:12, а детектирование в ультрафиолетовом свете после обработки нингидрином и с помощью KJ после хлорировани . Кроме этого , дл качественного и количественного определени конечного продукта примен ют HPLC. Детектирование провод т у аб- сорбционного максимума р-нитроанилина (315 нм) после отделени субстрата от продукта в С18-коло нке в ацетонитрильном градиенте . Дополнительно определ ют выход Z-Ala-Ala-Leu-р-нитроанилида гравиметри- ческим методом после повторной промывки NaHCO, и водой.in the system n-butanol: pyridine: acetic acid: water in the ratio 10: 15: 3: 12, and detection in ultraviolet light after treatment with ninhydrin and using KJ after chlorination. In addition, HPLC is used for the qualitative and quantitative determination of the final product. Detection is carried out at the absorption peak of p-nitroaniline (315 nm) after separation of the substrate from the product in the C18 column in the acetonitrile gradient. Additionally, the yield of Z-Ala-Ala-Leu-p-nitroanilide is determined by a gravimetric method after repeated washing with NaHCO3 and water.
Пример 2. 74 мг Z-Ala-Ala и 62 мг Leu-p-нитроанилида раствор ют в 250 мкл диметилформамида и смешивают с 300 мкл 50 мМ трис-HCI, рН 7,5, с 1 мМ Са-ацетата. Общий объем составл ет 900 мкл, а концентраци субстратов по 250 мкмоль. После чего довод т температуру до 35 °С, добавл ют 10 мкг фермента из Вас, cereus ZIMET 10700, очищенного аффинной хроматографией , и перемешивают 18 ч при 35°С. Выход Z-Ala-Ala-Leu-р-нитроанилида составл ет 72%.Example 2. 74 mg of Z-Ala-Ala and 62 mg of Leu-p-nitroanilide are dissolved in 250 µl of dimethylformamide and mixed with 300 µl of 50 mM Tris-HCl, pH 7.5, with 1 mM Ca-acetate. The total volume is 900 µl and the substrate concentration is 250 µmol. Then bring the temperature to 35 ° C, add 10 µg of the enzyme from you, cereus ZIMET 10700, purified by affinity chromatography, and stir for 18 hours at 35 ° C. The yield of Z-Ala-Ala-Leu-p-nitroanilide is 72%.
Пример 3. 24,4 мг Z-Asp раствор ют в 30 мкл 6 н. NaOH и 42,2 мг PheOMe-HCI, раствор ют в 200 мкл диметилформамида и смешивают с 300 мкл 50 мМ трис-HCI, рНExample 3. 24.4 mg of Z-Asp are dissolved in 30 µl of 6N. NaOH and 42.2 mg of PheOMe-HCl is dissolved in 200 µl of dimethylformamide and mixed with 300 µl of 50 mM Tris-HCl, pH
7,5, с 1 мМ Са-ацетата. После нагрева до 35°С добавл ют 100 мкл фильтрата культуральной жидкости, содержащего 110 мкг фермента. После перемешивани в течение 24 ч выход составл ет 38%, Качественное и количественное определение Z-аспартама соответствует методу примера 1, причем детектирование разделенного HPLC продукта провод т у 220 нм.7.5, with 1 mM Ca-acetate. After heating to 35 ° C, 100 µl of the culture fluid filtrate containing 110 µg of the enzyme is added. After stirring for 24 hours, the yield is 38%. The qualitative and quantitative determination of Z-aspartame corresponds to the method of Example 1, and the HPLC-separated product is detected at 220 nm.
Пример 4, 122 мг Z-Asp раствор ют в 160 мкл 6н. NaOH и 211 мг PheOMe-HCI в 800 мкл 50 мМ трис-HCI, рН 7,5, с 1 мМ Са-ацетата. После нагрева до 35 С добавл ют 1 мг фермента, очищенного аффинной хроматографией, в 100 мкл 50 мМ трис-HCI, рН 7,5, с 1 мМ Са-ацетата. В результате перемешивани в течение 24 ч получают выход Z-аспартама 54%.Example 4, 122 mg of Z-Asp is dissolved in 160 µl of 6N. NaOH and 211 mg of PheOMe-HCI in 800 μl of 50 mM Tris-HCl, pH 7.5, with 1 mM Ca-acetate. After heating to 35 ° C, 1 mg of an enzyme purified by affinity chromatography is added in 100 µl of 50 mM Tris-HCl, pH 7.5, with 1 mM Ca-acetate. As a result of stirring for 24 hours, a yield of Z-aspartame of 54% is obtained.
Пример 5. Способ осуществл ют как в примере 4, причем четвертное количество реактандов раствор ют в 2,5 мл 50 мМ трис- HCI-ном буфере, рН 7,0, с 1,0 м.М Са-ацетата . После повышени температуры до 35°С добавл ют 3 мг фермента, очищенного аффинной хроматографией. Через 5 ч перемешивани твердый осадок удал ют центрифугированием, а надосадочную жидкость снова инкубируют. Образующийс в течение следующих 5 ч осадок оп ть центрифугируют и определ ют количество Z-аспартама . Общий выход составл ет 85%.Example 5. The method is carried out as in Example 4, with a quarter amount of reagents being dissolved in 2.5 ml of 50 mM Tris-HCl buffer, pH 7.0, with 1.0 mM Ca-acetate. After raising the temperature to 35 ° C, 3 mg of the enzyme purified by affinity chromatography is added. After 5 hours of stirring, the solid precipitate is removed by centrifugation, and the supernatant is again incubated. The precipitate formed over the next 5 hours is centrifuged again and the amount of Z-aspartame determined. The overall yield is 85%.
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD28488985A DD257174A3 (en) | 1985-12-20 | 1985-12-20 | PROCESS FOR PREPARING THE PEPTIDES Z ALA ALA LON P NITRANILIDE OR Z ASP ASP PHE OME WITH METALOPROTEASE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SU1664845A1 true SU1664845A1 (en) | 1991-07-23 |
Family
ID=5574763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU867774327A SU1664845A1 (en) | 1985-12-20 | 1986-11-03 | Method for obtaining peptides |
Country Status (2)
| Country | Link |
|---|---|
| DD (1) | DD257174A3 (en) |
| SU (1) | SU1664845A1 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6342476B1 (en) | 1994-05-24 | 2002-01-29 | Yeda Research & Development Company Limited | Copolymer-1 improvements in compositions of copolymers |
| US7163802B2 (en) | 1998-09-25 | 2007-01-16 | Yeda Research And Development Co., Ltd. | Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use |
| US7279172B2 (en) | 1998-07-23 | 2007-10-09 | Yeda Research And Development Co., Ltd. | Treatment of autoimmune conditions with copolymer 1 and related copolymers |
| US7425332B2 (en) | 1998-07-23 | 2008-09-16 | Yeda Research And Development Co., Ltd. | Treatment of autoimmune conditions with Copolymer 1 and related Copolymers |
| US7429374B2 (en) | 2001-12-04 | 2008-09-30 | Teva Pharmaceutical Industries, Ltd. | Process for the measurement of the potency of glatiramer acetate |
| US7495072B2 (en) | 2004-09-09 | 2009-02-24 | Teva Pharmaceutical Industries, Ltd. | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
| US7560100B2 (en) | 2004-09-09 | 2009-07-14 | Yeda Research And Development Co., Ltd. | Mixtures of polypeptides, compositions containing and processes for preparing same, for treating neurodegenerative diseases |
| US8536305B2 (en) | 2004-10-29 | 2013-09-17 | Sandoz Ag | Processes for preparing a polypeptide |
-
1985
- 1985-12-20 DD DD28488985A patent/DD257174A3/en not_active IP Right Cessation
-
1986
- 1986-11-03 SU SU867774327A patent/SU1664845A1/en active
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7625861B2 (en) | 1994-05-24 | 2009-12-01 | Yeda Research And Development Co., Ltd. | Copolymer-1 improvements in compositions of copolymers |
| US6362161B1 (en) | 1994-05-24 | 2002-03-26 | Yeda Research & Development Company Limited | Copolymer-1 improvements on compositions of copolymers |
| US6620847B2 (en) | 1994-05-24 | 2003-09-16 | Yeda Research And Development Co., Ltd. | Copolymer-1 improvements in compositions of copolymers |
| US6939539B2 (en) | 1994-05-24 | 2005-09-06 | Yeda Research & Development | Copolymer-1 improvements in compositions of copolymers |
| US6342476B1 (en) | 1994-05-24 | 2002-01-29 | Yeda Research & Development Company Limited | Copolymer-1 improvements in compositions of copolymers |
| US7199098B2 (en) | 1994-05-24 | 2007-04-03 | Yeda Research And Development Co., Ltd. | Copolymer-1 improvements in compositions of copolymers |
| US8367605B2 (en) | 1994-05-24 | 2013-02-05 | Yeda Research And Development Co. Ltd. | Copolymer-1 improvements in compositions of copolymers |
| US7279172B2 (en) | 1998-07-23 | 2007-10-09 | Yeda Research And Development Co., Ltd. | Treatment of autoimmune conditions with copolymer 1 and related copolymers |
| US7425332B2 (en) | 1998-07-23 | 2008-09-16 | Yeda Research And Development Co., Ltd. | Treatment of autoimmune conditions with Copolymer 1 and related Copolymers |
| US7163802B2 (en) | 1998-09-25 | 2007-01-16 | Yeda Research And Development Co., Ltd. | Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use |
| US7615359B2 (en) | 1998-09-25 | 2009-11-10 | Yeda Research And Development Co., Ltd. | Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use |
| US8399211B2 (en) | 1998-09-25 | 2013-03-19 | Yeda Research And Development Co., Ltd. | Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use |
| US7923215B2 (en) | 2001-12-04 | 2011-04-12 | Teva Pharmaceutical Industries, Ltd. | Process for the measurement of the potency of glatiramer acetate |
| US7429374B2 (en) | 2001-12-04 | 2008-09-30 | Teva Pharmaceutical Industries, Ltd. | Process for the measurement of the potency of glatiramer acetate |
| US8389228B2 (en) | 2001-12-04 | 2013-03-05 | Teva Pharmaceutical Industries, Ltd. | Process for the measurement of the potency of glatiramer acetate |
| US7560100B2 (en) | 2004-09-09 | 2009-07-14 | Yeda Research And Development Co., Ltd. | Mixtures of polypeptides, compositions containing and processes for preparing same, for treating neurodegenerative diseases |
| US7495072B2 (en) | 2004-09-09 | 2009-02-24 | Teva Pharmaceutical Industries, Ltd. | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
| US8536305B2 (en) | 2004-10-29 | 2013-09-17 | Sandoz Ag | Processes for preparing a polypeptide |
Also Published As
| Publication number | Publication date |
|---|---|
| DD257174A3 (en) | 1988-06-08 |
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