WO2006029393A2 - Process for preparation of mixtures of polypeptides using purified hydrobromic acid - Google Patents
Process for preparation of mixtures of polypeptides using purified hydrobromic acid Download PDFInfo
- Publication number
- WO2006029393A2 WO2006029393A2 PCT/US2005/032395 US2005032395W WO2006029393A2 WO 2006029393 A2 WO2006029393 A2 WO 2006029393A2 US 2005032395 W US2005032395 W US 2005032395W WO 2006029393 A2 WO2006029393 A2 WO 2006029393A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- solution
- mixture
- acetic acid
- acid
- hydrobromic acid
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4713—Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
Definitions
- a mixture of polypeptides which do not all have the same amino acid sequence referred to as glatiramer acetate (GA) is marketed under the tradename Copaxone® and comprises the acetate salts of polypeptides containing L- glutamic acid, L-alanine, L-tyrosine and L-lysine at average molar fractions of 0.141, 0.427, 0.095 and 0.338, respectively.
- the average molecular weight of Copaxone® is between 4,700 and 11,000 daltons.
- glatiramer acetate is designated L-glutamic acid polymer with L- alanine, L-lysine, L-tyrosine, acetate (salt) . Its structural formula is:
- Glatiramer acetate is approved for reduction of the frequency of relapses in patients with relapsing- remitting multiple sclerosis. Multiple sclerosis has been classified as an autoimmune disease. Glatiramer acetate has also been disclosed for use in the treatment of other autoimmune diseases (Publication No. US 2002/0055466 Al for R. Aharoni et al . ) , inflammatory non-autoimmune diseases (Publication No. US 2005/0014694 Al for V. Wee Yong et al . ; and U.S. Patent Application No. 2002/0077278 Al, published June 20, 2002 (Young et al .
- This invention provides an improved manufacturing process.
- the subject invention provides a process for obtaining a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacetyl lysine, wherein the mixture has a desired average molecular weight and wherein during the process a batch of a mixture of polypeptides, each of which consists essentially of alanine, ⁇ -benzyl glutamate, tyrosine and trifluoroacetyl lysine is deprotected with a solution of hydrobromic acid in acetic acid, the improvement comprising use of a solution of hydrobromic acid in acetic acid, which solution comprises less than 0.5% of free bromine.
- the subject invention also provides a process for obtaining a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacetyl lysine, wherein the mixture has a desired average molecular weight and wherein during the process a batch of a mixture of polypeptides, each of which consists essentially of alanine, ⁇ -benzyl glutamate, tyrosine and trifluoroacetyl lysine is deprotected with a solution of hydrobromic acid in acetic acid, the improvement comprising use of a solution of hydrobromic acid in acetic acid, which solution comprises less than 1000 ppm of metal ion impurities.
- the subject invention further provides process of producing a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacetyl lysine, wherein the mixture has a desired average molecular weight comprising deprotecting a mixture of polypeptides each consisting essentially of alanine, ⁇ -benzyl glutamate, tyrosine and trifluoroacetyl lysine with a solution of hydrobromic acid in acetic acid, which solution comprises less than 0.5% of free bromine and less than 1000 ppm of metal ion impurities .
- the subject invention also provides a composition comprising the trifluoroacetyl product produced by any one of the subject invention processes, and a carrier.
- the subject invention further provides a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacetyl lysine, wherein the mixture has a desired average molecular weight, no more than 0.1% brominated tyrosine and less than 1000 ppm metal ion impurities.
- the subject invention also provides a composition comprising the mixture of trifluoroacetyl polypeptides and a carrier.
- the subject invention also provides process for obtaining a pharmaceutical composition containing a mixture of polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and lysine, and wherein the mixture has a desired average molecular weight, which comprises a) polymerizing N-carboxyanhydrides of tyrosine, alanine, ⁇ -benzyl glutamate and N- trifluoroacetyl lysine to form a mixture of protected polypeptides;
- the subjection invention further provides process of producing glatiramer acetate comprising the steps of:
- the subject invention yet further provides a method of analyzing the percentage of brominated tyrosine in a sample of glatiramer acetate comprising the steps of:
- the subject invention also provides a process for preparing a pharmaceutical composition containing a mixture of polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of glutamic acid, alanine, tyrosine and lysine, wherein the mixture has a predetermined percentage of brominated tyrosine acceptable for inclusion in a pharmaceutical composition, which comprises obtaining a batch of a mixture of polypeptides having nonuniform amino acid sequences, where each polypeptide consists essentially of glutamic acid, alanine, tyrosine and lysine; measuring the percentage of brominated tyrosine of the batch by a process comprising
- the subject invention provides a process for obtaining a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacetyl lysine, wherein the mixture has a desired average molecular weight and wherein during the process a batch of a mixture of polypeptides, each of which consists essentially of alanine, ⁇ -benzyl glutamate, tyrosine and trifluoroacetyl lysine is deprotected with ' a solution of hydrobromic acid in acetic acid, the improvement comprising use of a solution of hydrobromic acid in acetic acid, which solution comprises less than 0.5% of free bromine.
- the improvement further comprises use of a solution of hydrobromic acid in acetic acid that comprises less than 1000 ppm of metal ion impurities.
- the subject invention further provides a process for obtaining a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacetyl lysine, wherein the mixture has a desired average molecular weight and wherein during the process a batch of a mixture of polypeptides, each of which consists essentially of alanine, ⁇ -benzyl glutamate, tyrosine and trifluoroacetyl lysine is deprotected with a solution of hydrobromic acid in acetic acid, the improvement comprising use of a solution of hydrobromic acid in acetic acid, which solution comprises less than 1000 ppm of metal ion impurities .
- the subject invention yet further provides a process of producing a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacetyl lysine, wherein the mixture has a desired average molecular weight comprising deprotecting a mixture of polypeptides each consisting essentially of alanine, ⁇ -benzyl glutamate, tyrosine and trifluoroacetyl lysine with a solution of hydrobromic acid in acetic acid, which solution comprises less than 0.5% of free bromine and less than 1000 ppm of metal ion impurities .
- ' a process of producing a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacety
- the solution of hydrobromic acid in acetic acid comprises less than 0.1% of free bromine.
- the solution of hydrobromic acid in acetic acid comprises less than 0.05% of free bromine.
- the solution of hydrobromic acid in acetic acid comprises less than 0.01% of free bromine.
- the solution of hydrobromic acid in acetic acid comprises less than 0.001% of free bromine .
- the solution of hydrobromic acid in acetic acid is free of free bromine.
- the solution of hydrobromic acid in acetic acid comprises less than 1000 ppm of metal ion impurities .
- the solution of hydrobromic acid in acetic acid comprises less than 500 ppm of metal ion impurities.
- the solution of hydrobromic acid in acetic acid comprises less than 100 ppm of metal ion impurities .
- the solution of hydrobromic acid in acetic acid comprises less than 30 ppm of metal ion impurities .
- the solution of hydrobromic acid in acetic acid comprises less than 20 ppm of metal ion impurities.
- the solution of hydrobromic acid in acetic acid comprises less than 10 ppm of metal ion impurities .
- the solution of hydrobromic acid in acetic acid is free of metal ion impurities.
- the mixture of trifluoroacetyl polypeptides is trifluoroacetyl glatiramer acetate ("TFA GA") .
- the hydrobromic acid in acetic acid solution is from 10% to 36% hydrobromic acid in acetic acid.
- the hydrobromic acid in acetic acid is from 16% to 33% hydrobromic acid in acetic acid; 18% to 33% hydrobromic acid in acetic acid; 20% to 37% hydrobromic acid in acetic acid; 20% to 33% hydrobromic acid in acetic acid; 22% to 33% hydrobromic acid in acetic acid; 24% to 33% hydrobromic acid in acetic acid; 25% to 35% hydrobromic acid in acetic acid; 26% to 33% hydrobromic acid in acetic acid; 28% to 33% hydrobromic acid in acetic acid; 30% to 34% hydrobromic acid is acetic acid; 30% to 33% hydrobromic acid in acetic acid; or 32% to 33% hydrobromic acid in acetic acid.
- the solution is 33% hydrobromic acid in acetic acid.
- the solution is 16% hydrobromic acid in acetic acid.
- the solution is pretreated with a bromine scavenger in order to remove free bromine.
- the bromine scavenger is phenol
- the solution is produced in a non-metallic reactor.
- the solution is prepared in a glass-lined or Teflon lined reactor.
- the color of the hydrobromic acid in acetic acid solution is less than 2000 APHA.
- the color of the hydrobromic acid in acetic acid solution is less than 1000 APHA.
- the color of the hydrobromic acid in acetic acid solution is less than 700 APHA. In yet another embodiment, the color of the hydrobromic acid in acetic acid solution is less than 500 APHA.
- the subject invention also provides a trifluoroacetyl product produced by any one of the disclosed processes.
- the subject invention further provides a composition comprising the trifluoroacetyl product produced by any one of the disclosed processes, and a carrier.
- the subject invention yet further provides a mixture of trifluoroacetyl polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and trifluoroacetyl lysine, wherein the mixture has a desired average molecular weight, no more than 0.1% brominated tyrosine and less than 1000 ppm metal ion impurities.
- the mixture of trifluoroacetyl polypeptides has an average molecular weight from 2000 daltons to 40,000 daltons .
- the mixture of trifluoroacetyl polypeptides has an average molecular weight from 4000 daltons to 18,000 daltons.
- the mixture of trifluoroacetyl polypeptides has an average molecular weight from 4000 daltons to 13,000 daltons.
- the mixture of trifluoroacetyl polypeptides has an average molecular weight from 13,000 daltons to 19,000 daltons. In yet another embodiment, the mixture of trifluoroacetyl polypeptides has an average molecular weight from 13,500 daltons to 18,500 daltons .
- the mixture of trifluoroacetyl polypeptides has an average molecular weight of 7,000 ⁇ 2, 000 daltons .
- the mixture of trifluoroacetyl polypeptides has an average molecular weight of 7,000 daltons.
- the mixture of trifluoroacetyl polypeptides has an average molecular weight of 14,000 daltons .
- the mixture of trifluoroacetyl polypeptides has an average molecular weight from 4,700 - 11, 000 daltons.
- the mixture of trifluoroacetyl polypeptides comprises less than 1000 ppm of metal ion impurities .
- the mixture of trifluoroacetyl polypeptides comprises less than 500 ppm of metal ion impurities .
- the mixture of trifluoroacetyl polypeptides comprises less than 100 ppm of metal ion impurities . In another embodiment, the mixture of trifluoroacetyl polypeptides comprises less than 30 ppm of metal ion impurities .
- the mixture of trifluoroacetyl polypeptides comprises less than 20 ppm of metal ion impurities .
- the mixture of trifluoroacetyl polypeptides comprises, less than 10 ppm of metal ion impurities .
- the mixture of trifluoroacetyl polypeptides is free of metal ion impurities.
- the subject invention also provides a composition comprising the mixture of trifluoroacetyl polypeptides and a carrier.
- the subject invention further provides a process for obtaining a pharmaceutical composition containing a mixture of polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of alanine, glutamic acid, tyrosine and lysine, and wherein the mixture has a desired average molecular weight, which comprises a) polymerizing N-carboxyanhydrides of tyrosine, alanine, ⁇ -benzyl glutamate and N-trifluoroacetyl lysine to form an aqueous mixture of protected polypeptides;
- the average mole fraction in the mixture is glutamic acid 0.129-0.159; alanine 0.392- 0.462; tyrosine 0.086-0.100; and lysine 0.300-0.374.
- the average mole fraction in the mixture of glutamic acid is 0.141, of alanine is 0.427, of tyrosine is 0.093, and of lysine is 0.337.
- the subject invention also provides a process of producing glatiramer acetate comprising the steps of:
- the product of the step d) is further subjected to ultrafiltration to remove polypeptide species with molecular weight less than 5000 daltons.
- the hydrobromic acid in acetic acid solution is from 10% to 36% hydrobromic acid in acetic acid.
- the hydrobromic acid in acetic acid is from 16% to 33% hydrobromic acid in acetic acid; 18% to 33% hydrobromic acid in acetic acid; 20% to 37% hydrobromic acid in acetic acid; 20% to 33% hydrobromic acid in acetic acid; 22% to 33% hydrobromic acid in acetic acid; 24% to 33% hydrobromic acid in acetxc acid; 25% to 35% hydrobromic acid in acetic acid; 26% to 33% hydrobromic acid in acetic acid; 28% to 33% hydrobromic acid in acetic acid; 30% to 34% hydrobromic acid is acetic acid; 30% to 33% hydrobromic acid in acetic acid; or 32% to 33% hydrobromic acid in acetic acid.
- the solution is 33% hydrobromic acid in acetic acid.
- the solution is 16%
- the hydrobromic acid in acetic acid solution is pretreated with a bromine scavenger in order to remove free bromine.
- the bromine scavenger is phenol .
- the hydrobromic acid in acetic acid solution is produced in a non-metallic reactor.
- the hydrobromic acid in acetic acid solution is prepared in a glass-lined or Teflon lined reactor.
- the color of the hydrobromic acid in acetic acid solution is less than 2000 APHA.
- the color of the hydrobromic acid in acetic acid solution is less than 1000 APHA.
- the color of the hydrobromic acid in acetic acid solution is less than 700 APHA.
- the color of the hydrobromic acid in acetic acid solution is less than 500 APHA.
- the subject invention further provides method of analyzing the percentage of brominated tyrosine in a sample of glatiramer acetate comprising the steps of:
- the subject invention also provides a process for preparing a pharmaceutical composition containing a mixture of polypeptides which do not all have the same amino acid sequence, where each polypeptide consists essentially of glutamic acid, alanine, tyrosine and lysine, wherein the mixture has a predetermined percentage of brominated tyrosine acceptable for inclusion in a pharmaceutical composition, which comprises obtaining a batch of a mixture of polypeptides having nonuniform amino acid sequences, where each polypeptide consists essentially of glutamic acid, alanine, tyrosine and lysine; measuring the percentage of brominated tyrosine of the batch by a process comprising
- step b) eluting the sample solutions through the column of step b) ; and f) calculating the percentage of brominated tyrosine in the batch; and including in the pharmaceutical composition a batch only if its percentage of brominated tyrosine so measured is less than 0.3%.
- the batch is acceptable for inclusion in the pharmaceutical composition only if its percentage of brominated tyrosine so measured is less than 0.2%.
- the batch is acceptable for inclusion in the pharmaceutical composition only if its percentage of brominated tyrosine so measured is less than
- the mixture of polypeptides is glatiramer acetate ("GA") .
- average molecular weight means the molecular weight of the species of polypeptides present in the mixture in the highest relative proportion (i.e. the peak maximum) when the mixture is subjected to separation by molecular weight on an HPLC gel permeation column. This value can be obtained in several ways, e.g. from the retention time on a calibrated column; or from a correlation between the location of the peak and the location of the cochromatographed copolymer markers of defined sequence and molecular weight. Other methods of determining an average molecular weight such as by light scattering may be employed and will correspond substantially to the value obtained from the peak maximum.
- a polypeptide mixture according to this invention as exemplified is the acetate salt of synthetic polypeptides prepared by chemically reacting four activated amino acid derivatives (two of them L-Glutamic acid and L-lysine protected) : L-Glutamic acid (L-GIu) , L-alanine (L- AIa) , L-tyrosine (L-Tyr) and L-lysine (L-Lys) (two of them protected i.e. 5Bz-Glutamate derivative and 6N-TFA- Lysine derivative) in a specified ratio.
- mixture generally refers to in the “mixture of polypeptides of the invention” comprising L-glutamic acid, L-alanine, L-tyrosine, and L-lysine, and both terms are meant to include residual impurities from the manufacturing process.
- the molar fraction range of each amino acid residue is: L-GIu 0.129-0.153, L-AIa 0.392-0.462, L-Tyr 0.086-0.100 and L-Lys 0.300-0.374.
- impurities may be of the following three types :
- polypeptide mixture of the invention molecules may contain brominated L-tyrosyl residues, formed during production due to the presence of free bromine in the HBr/acetic acid reagent.
- the molecular structures of the identified structure-related impurities can be derived from the participating monomers i.e. starting materials.
- Unidentified related substances are small molecular size polypeptides of the same origin with similar structures. These substances probably have similar response factors and the concentration (%) of each impurity can be calculated as % peak area relative to the the polypeptide mixture of the invention peak area.
- the characterization of the impurities is based on their relative chromatography retention time (RRT] relative to the L-Tryptophan standard.
- Residual solvents and inorganic impurities covered in the specification such as the residual solvent 1,4 dioxane, residual piperidine and heavy metals.
- the inventors discovered that the brominated tyrosine impurity was introduced into the GA through free bromine in HBr/acetic acid.
- the free bromine was present in 33% HBr/acetic acid bought from a supplier and used in the production process.
- Measures were taken in order to decrease the level of free bromine in 33% HBr/acetic acid.
- pre-treatment of HBr/acetic acid with a bromine scavenger was effective in removing some of the free bromine from the HBr/acetic acid solution.
- One of the bromine scavengers used in the HBr purification process was phenol.
- other reducing agents such as sodium bisulfite, may be used.
- Phenol was chosen as a bromine scavenger because it and its reaction product with bromine (bromophenols) are both essentially non-reactive with protected polypeptides, such as protected GA, TFA polypeptides, such as TFA GA and polypeptides, such as GA, and they are easy to remove from the solution of GA during the purification process.
- any bromine scavenging agent may be used provided that it, and its reaction product with bromine, are not reactive with protected polypeptides, such as protected GA, TFA polypeptides, such as TFA GA and polypeptides, such as GA, and it is easily removable during the final purification process.
- GA is marketed in two pharmaceutical dosage forms, lyophilized powder and pre-filled syringes.
- the syringes marketed under the trade name Copaxone® Injection, generally contained clear solution.
- the storage instructions were to keep the syringes refrigerated.
- a non-metal reactor for the production of 33% HBr/acetic acid solution.
- the reactor used for the production of HBr/acetic acid solution was glass lined in order to prevent the formation of impurities which could later affect the purity of, e.g., the GA.
- parts of the piping used were Teflon-lined.
- other types of non-reactive, acid resistant non-metal apparatus can be used to prevent the formation of trace metal ions in the HBr/acetic acid solution.
- HBr solution with a color below 2000 APHA was shown to produce glatiramer acetate without red color.
- Standard solutions containing 2 ⁇ g/mL Bromotyrosine were ' prepared using distilled water.
- Amino acid standard stock solution was prepared using the following amino acids:
- the amino acids were dissolved in water. A few drops of 5 N NaOH were added and water was added to a final volume of 25 ⁇ iL .
- a negative control vial was prepared by adding 0.5 mL of the amino acid standard stock solution to a 5 mL hydrolysis vial. 0.5 mL of water and 0.5 mL of concentrated HCl containing 1% of phenol were added to each of the vials. The vials were heated to 110 0 C for 24 hours, under N 2 atmosphere. The samples were then cooled to room temperature. Each of the hydrolyzates were transferred to 5 mL volumetric flasks and filled to volume with distilled water.
- the bromotyrosine standard, and each of the hydrolyzates, were independently eluted through an HPLC column using an eluent of acetonitrile : water : acetic acid in a ratio of 4 : 95 : 1.
- the column was equipped with an UV detector and data recording system.
- the amino acid standard is used as a negative control to determine which peak in the glatiramer acetate hydiolyzate corresponds to bromotyrosine .
- Table 1 shows the effect of free Bromine on the level of brominated tyrosine moiety in TFA Glatiramer Acetate and in Glatiramer Acetate
- the glass-lined reactor is rinsed with acetic acid, then emptied. 1013 kg of acetic acid is added into the reactor.
- the acetic acid is maintained at a temperature of 10-20 0 C. 522 kg of HBr gas is introduced into the reactor while mixing the solution. After the gas is introduced, the solution is mixed for an additional 30 minutes. The solution is tested to determine if HBr content is 33%.
- HBr solution in a weight ratio of 1 to 100. The solution was then stirred for 12 to 24 hours. The purified HBr solution is then added to protected glatiramer acetate.
- the reaction of the HBr with protected GA forms TFA GA.
- the TFA GA is reacted with piperidine to form GA.
- the level of Brominated tyrosine moiety in various batches of glatiramer acetate was measured using the method described in example 1.
- the color of the HBr/acetic acid solution was determined using standard visual color determination techniques.
- the American Public Health Association (APHA) color index is a single number yellowness index where each APHA unit is based on a dilution of the 500 ppm stock solution of platinum-cobalt (PtCo) .
- PtCo platinum-cobalt
- the APHA measurement is determined by visual comparison of the solution with PtCo standards that contain controlled amounts of potassium chloroplatinate and cobaltous chloride. Each number unit is the equivalent of 1 mg of platinum per liter of solution (ppm) .
- the standards and corresponding measurements are designated according to their ppm measurement, i.e. the No. 20 APHA standard contains 20 ppm of platinum.
- distille water has an APHA value of 0
- the stock solution has an APHA value of 500 ppm.
- HunterLab APHA Background, Applications Not, Insight on Color, November 16-30, 1996, Vol. 8, No. 16. available at http: //www.hunterlab. com/appnotes/anll 96br2.pdf.
- the APHA measurement may be made by various instruments well known in the art.
- APHA color standard "500” and APHA color standard "1000” were prepared.
- APHA color standard "500” was prepared by dissolving 1.246 g Potassium Chloroplatinate, K 2 PtCl 6 (equivalent to 50 mg metallic Platinum) and 1.00 g crystallized Cobaltous Chloride, C0CI 2 -6H 2 O (equivalent to about 250 mg metallic Cobalt) in distilled water with 100 ml concentrated HCl and was diluted to 1000 mL with distilled water.
- APHA color standard "1000" was prepared by dissolving 2.492 g Potassium Chloroplatinate K 2 PtCl 6 and 2.00 g crystallized Cobaltous Chloride CoCl 2 -6H 2 0 in distilled water with 200 mL concentrated HCl and was diluted to 1000 mL with distilled water.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Rehabilitation Therapy (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (21)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2007531423A JP5149008B2 (en) | 2004-09-09 | 2005-09-09 | Method for preparing a polypeptide mixture using purified hydrobromic acid |
BRPI0515033-7A BRPI0515033B1 (en) | 2004-09-09 | 2005-09-09 | PROCESS FOR OBTAINING A MIXTURE OF TRIFLUOROACETYL POLYPEPTIDES, MIXTURE OF TRIFLUOROACETYL POLYPEPTIDES, AND PROCESSES FOR OBTAINING A PHARMACEUTICAL COMPOSITION AND FOR THE PRODUCTION OF GLATIRAMER ACETATE |
NZ554018A NZ554018A (en) | 2004-09-09 | 2005-09-09 | Process for preparation of trifluoroacetyl glatiramer acetate using purified hydrobromic acid |
PL05791236T PL1799703T3 (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
DK05791236.2T DK1799703T3 (en) | 2004-09-09 | 2005-09-09 | Process for Preparing Mixtures of Polypeptides by Purified Hydrogen Bromide |
CN200580033851.5A CN101166754B (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
CA2579656A CA2579656C (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
AT05791236T ATE454396T1 (en) | 2004-09-09 | 2005-09-09 | METHOD FOR PRODUCING POLYPEPTIDE MIXTURES USING PURIFIED HYDROCROMIC ACID |
UAA200703838A UA91029C2 (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
DE602005018800T DE602005018800D1 (en) | 2004-09-09 | 2005-09-09 | METHOD FOR THE PRODUCTION OF POLYPEPTIDE MIXTURES USING PURIFICED BROMINE HYDROGEN ACID |
AU2005282249A AU2005282249B2 (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
EP05791236A EP1799703B1 (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
RSP-2010/0114A RS51257B (en) | 2004-09-09 | 2005-09-09 | Process forpreparation of mixtures of polupeptides using purified hydrobromic acid |
KR1020077007738A KR101317131B1 (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
MX2007002760A MX2007002760A (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid. |
IL181596A IL181596A (en) | 2004-09-09 | 2007-02-27 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
IS8622A IS8622A (en) | 2004-09-09 | 2007-03-16 | Method of Preparation of Polypeptide Preparations Using Purified Hydrochloric Acid |
NO20071632A NO20071632L (en) | 2004-09-09 | 2007-03-28 | Process for the preparation of polypeptide mixtures using purified hydrobromic acid |
HK07108827.5A HK1100780A1 (en) | 2004-09-09 | 2007-08-14 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
HR20100164T HRP20100164T1 (en) | 2004-09-09 | 2010-03-19 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
IL241702A IL241702A0 (en) | 2004-09-09 | 2015-09-17 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US60884304P | 2004-09-09 | 2004-09-09 | |
US60/608,843 | 2004-09-09 |
Publications (3)
Publication Number | Publication Date |
---|---|
WO2006029393A2 true WO2006029393A2 (en) | 2006-03-16 |
WO2006029393A8 WO2006029393A8 (en) | 2007-04-19 |
WO2006029393A3 WO2006029393A3 (en) | 2007-12-13 |
Family
ID=36037047
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2005/032395 WO2006029393A2 (en) | 2004-09-09 | 2005-09-09 | Process for preparation of mixtures of polypeptides using purified hydrobromic acid |
Country Status (28)
Country | Link |
---|---|
US (2) | US7495072B2 (en) |
EP (3) | EP2177528B1 (en) |
JP (1) | JP5149008B2 (en) |
KR (1) | KR101317131B1 (en) |
CN (1) | CN101166754B (en) |
AT (2) | ATE454396T1 (en) |
AU (1) | AU2005282249B2 (en) |
BR (1) | BRPI0515033B1 (en) |
CA (1) | CA2579656C (en) |
CY (1) | CY1110280T1 (en) |
DE (1) | DE602005018800D1 (en) |
DK (3) | DK2177528T3 (en) |
ES (3) | ES2382298T3 (en) |
HK (3) | HK1100780A1 (en) |
HR (3) | HRP20100164T1 (en) |
IL (2) | IL181596A (en) |
IS (1) | IS8622A (en) |
MX (1) | MX2007002760A (en) |
NO (1) | NO20071632L (en) |
NZ (1) | NZ554018A (en) |
PL (3) | PL2361924T3 (en) |
PT (3) | PT1799703E (en) |
RS (3) | RS53248B (en) |
RU (1) | RU2388764C2 (en) |
SI (3) | SI2177528T1 (en) |
UA (1) | UA91029C2 (en) |
WO (1) | WO2006029393A2 (en) |
ZA (1) | ZA200702591B (en) |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009129018A1 (en) * | 2008-04-16 | 2009-10-22 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
WO2010115175A1 (en) | 2009-04-03 | 2010-10-07 | Momenta Pharmaceticals, Inc. | Control of copolymer compositions |
WO2012123959A2 (en) | 2011-02-14 | 2012-09-20 | Usv Limited | Copolymer-1, process for preparation and analytical methods thereof |
US8324348B1 (en) | 2011-07-11 | 2012-12-04 | Momenta Pharmaceuticals, Inc. | Evaluation of copolymer diethylamide |
EP2563804A2 (en) * | 2010-04-27 | 2013-03-06 | Dr. Reddy's Laboratories Ltd. | Preparation of polypeptides and salts thereof |
US9155775B1 (en) | 2015-01-28 | 2015-10-13 | Teva Pharmaceutical Industries, Ltd. | Process for manufacturing glatiramer acetate product |
US9617596B2 (en) | 2012-10-10 | 2017-04-11 | Teva Pharmaceutical Industries, Ltd. | Biomarkers predictive for clinical response for glatiramer acetate |
US9625473B2 (en) | 2010-10-11 | 2017-04-18 | Teva Pharmaceutical Industries Ltd. | Cytokine biomarkers as predictive biomarkers of clinical response for glatiramer acetate |
US9702007B2 (en) | 2013-10-21 | 2017-07-11 | Teva Pharmaceuticals Industries, Ltd. | Genetic markers predictive of response to glatiramer acetate |
US11167003B2 (en) | 2017-03-26 | 2021-11-09 | Mapi Pharma Ltd. | Methods for suppressing or alleviating primary or secondary progressive multiple sclerosis (PPMS or SPMS) using sustained release glatiramer depot systems |
EP3199544B1 (en) * | 2014-09-26 | 2021-11-17 | Hybio Pharmaceutical Co., Ltd | Preparation method for glatiramer acetate |
USRE49251E1 (en) | 2010-01-04 | 2022-10-18 | Mapi Pharma Ltd. | Depot systems comprising glatiramer or pharmacologically acceptable salt thereof |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1098902A4 (en) | 1998-07-23 | 2002-07-24 | Yeda Res & Dev | Treatment of autoimmune conditions with copolymer 1 and related copolymers and peptides |
ES2527760T3 (en) * | 1998-07-23 | 2015-01-29 | Yeda Research And Development Co., Ltd. | Treatment of Crohn's disease with copolymer 1 and polypeptides |
US6800287B2 (en) | 1998-09-25 | 2004-10-05 | Yeda Research And Development Co., Ltd. | Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use |
WO2002076503A1 (en) * | 2000-06-20 | 2002-10-03 | Mayo Foundation For Medical Education And Research | Treatment of central nervous system diseases by antibodies against glatiramer acetate |
US7429374B2 (en) * | 2001-12-04 | 2008-09-30 | Teva Pharmaceutical Industries, Ltd. | Process for the measurement of the potency of glatiramer acetate |
CA2558380A1 (en) * | 2004-03-03 | 2005-09-15 | Teva Pharmaceutical Industries, Ltd. | Combination therapy with glatiramer acetate and riluzole |
WO2006029411A2 (en) * | 2004-09-09 | 2006-03-16 | Yeda Research And Development Co. Ltd. | Mixtures of polypeptides, compositions containing and processes for preparing same, and uses thereof |
NZ554018A (en) * | 2004-09-09 | 2009-06-26 | Teva Pharma | Process for preparation of trifluoroacetyl glatiramer acetate using purified hydrobromic acid |
US8324641B2 (en) * | 2007-06-29 | 2012-12-04 | Ledengin, Inc. | Matrix material including an embedded dispersion of beads for a light-emitting device |
AR052321A1 (en) * | 2004-10-29 | 2007-03-14 | Sandoz Ag | PROCESSES FOR THE PREPARATION OF A POLYPEPTIDE |
US20060172942A1 (en) * | 2005-02-02 | 2006-08-03 | Teva Pharmaceutical Industries, Ltd. | Process for producing polypeptide mixtures using hydrogenolysis |
SI1848415T1 (en) * | 2005-02-17 | 2013-08-30 | Teva Pharmaceutical Industries Ltd. | Combination therapy with glatiramer acetate and rasagiline for the treatment of multiple sclerosis |
EP1891233A4 (en) * | 2005-04-25 | 2010-03-24 | Yeda Res & Dev | Markers associated with the therapeutic efficacy of glatiramer acetate |
US20090035816A1 (en) * | 2007-08-02 | 2009-02-05 | Scinopharm Taiwan Ltd. | Process for the preparation of a polypeptide |
EA201070656A1 (en) * | 2007-11-28 | 2010-12-30 | Тева Фармасьютикал Индастриз, Лтд. | METHOD OF DELAYING THE BEGINNING OF MANIFESTATION OF CLINICALLY DEFINED SCATTERED SCLEROSIS |
PL2307448T3 (en) * | 2008-08-07 | 2015-10-30 | Sigma Aldrich Co Llc | Preparation of low molecular weight polylysine and polyornithine in high yield |
WO2010017292A1 (en) * | 2008-08-07 | 2010-02-11 | Scinopharm Taiwan, Ltd. | Synthesis of glatiramer acetate |
RS52885B (en) | 2009-08-20 | 2014-02-28 | Yeda Research And Development Co. Ltd. | Low frequency glatiramer acetate therapy |
US8759302B2 (en) | 2010-03-16 | 2014-06-24 | Teva Pharmaceutical Industries, Ltd. | Methods of treating a subject afflicted with an autoimmune disease using predictive biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis |
JP5701103B2 (en) * | 2011-03-02 | 2015-04-15 | 昭和シェル石油株式会社 | Antifoam composition for lubricating oil and defoaming method using the same |
ES2601892T3 (en) | 2011-04-21 | 2017-02-16 | Mapi Pharma Limited | Random Pentapolymer for the treatment of autoimmune diseases |
WO2013009864A1 (en) | 2011-07-11 | 2013-01-17 | Momenta Pharmaceuticals, Inc. | Structure assessment of heterogeneous polypeptide mixtures |
US8575198B1 (en) | 2011-09-07 | 2013-11-05 | Momenta Pharmaceuticals, Inc. | In-process control for the manufacture of glatiramer acetate |
EA201490749A1 (en) | 2011-10-10 | 2014-09-30 | Тева Фармасьютикал Индастриз Лтд. | ONE-NUCLEOTIC POLYMORPHISMS USEFUL FOR PREDICTING CLINICAL REACTION TO GLETYRAMER ACETATE |
CN102717992A (en) * | 2012-05-30 | 2012-10-10 | 苏州市旭洋工业搪瓷厂 | Glass lining made bromine storage tank |
CN102718963B (en) * | 2012-06-19 | 2014-10-15 | 深圳翰宇药业股份有限公司 | Preparation method of polymer polypeptide |
WO2015066515A1 (en) | 2013-11-01 | 2015-05-07 | Receptos, Inc. | Selective sphingosine 1 phosphate receptor modulators and combination therapy therewith |
US20190202984A1 (en) * | 2018-01-03 | 2019-07-04 | Kinbio Ltd. | Process of preparing glatiramer acetate |
Family Cites Families (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3846550A (en) | 1971-01-21 | 1974-11-05 | H Akrongold | Cosmetic skin powder containing urea |
IL36670A (en) * | 1971-04-21 | 1974-09-10 | Sela M | Therapeutic basic copolymers of amino acids |
JPS54119499A (en) * | 1978-03-09 | 1979-09-17 | Shionogi & Co Ltd | Triazolobenzodiazepin derivative |
JPS6053535A (en) | 1983-09-02 | 1985-03-27 | Nitto Boseki Co Ltd | Production of regular polyaminoacid resin |
SU1182051A1 (en) | 1984-04-28 | 1985-09-30 | Таджикский государственный университет им.В.И.Ленина | Polytripeptides possessing oenantic selectivity in reactions of hydrolysis of carbobenzoxy-d-1 alanine n-nitrophenyl esters |
ATE73338T1 (en) | 1985-06-18 | 1992-03-15 | Univ Emory | BIOLOGICALLY ACTIVE COPOLYMERS. |
DD257174A3 (en) | 1985-12-20 | 1988-06-08 | Ve Forschungszentrum Biotechno | PROCESS FOR PREPARING THE PEPTIDES Z ALA ALA LON P NITRANILIDE OR Z ASP ASP PHE OME WITH METALOPROTEASE |
SU1469826A1 (en) | 1986-05-30 | 1995-11-20 | Институт Высокомолекулярных Соединений Ан Ссср | Copolymer of l-lysine and l-glutamic acid containing side groups and showing prolonged hypotensive activity and compensatory effect at hemorrhagic shock, and a method of its preparing |
SU1690368A1 (en) | 1989-07-20 | 1995-08-20 | Институт Высокомолекулярных Соединений Ан Ссср | Statistic copolymers as low toxic compounds having prolonged hypotensive action and method for their production |
DE3930733A1 (en) | 1989-09-14 | 1991-03-28 | Roehm Gmbh | METHOD FOR PRODUCING A COMPLEX MEDICINAL PRODUCT |
USH1312H (en) * | 1992-05-28 | 1994-05-03 | Cytogen Corporation | Method for the preparation of gyk-dtpa |
US5800808A (en) * | 1994-05-24 | 1998-09-01 | Veda Research And Development Co., Ltd. | Copolymer-1 improvements in compositions of copolymers |
US5858964A (en) | 1995-04-14 | 1999-01-12 | Yeda Research And Development Co. Ltd. | Pharmaceutical compositions comprising synthetic peptide copolymer for prevention of GVHD |
FR2750423B1 (en) | 1996-06-28 | 1998-08-14 | Rhone Poulenc Chimie | PROCESS FOR THE ASYMMETRIC HYDROGENATION OF A KETONIC COMPOUND |
US6214791B1 (en) | 1997-01-10 | 2001-04-10 | Yeda Research And Development Co. Ltd. | Treatment of multiple sclerosis through ingestion or inhalation of copolymer-1 |
DK1031563T3 (en) | 1997-09-30 | 2006-05-08 | Daiichi Seiyaku Co | sulphonyl derivatives |
US5872122A (en) * | 1997-10-16 | 1999-02-16 | Monsanto Company | Pyrimidinylamidino β-amino acid derivatives useful as inhibitors of platelet aggregation |
US5965047A (en) | 1997-10-24 | 1999-10-12 | Steag Ast | Rapid thermal processing (RTP) system with rotating substrate |
GB9724627D0 (en) | 1997-11-20 | 1998-01-21 | Genencor Int Bv | Gram positive microorganism formate pathway |
ES2527760T3 (en) | 1998-07-23 | 2015-01-29 | Yeda Research And Development Co., Ltd. | Treatment of Crohn's disease with copolymer 1 and polypeptides |
EP1098902A4 (en) | 1998-07-23 | 2002-07-24 | Yeda Res & Dev | Treatment of autoimmune conditions with copolymer 1 and related copolymers and peptides |
US6800287B2 (en) | 1998-09-25 | 2004-10-05 | Yeda Research And Development Co., Ltd. | Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use |
US6514938B1 (en) | 1998-09-25 | 2003-02-04 | Yeda Research And Development Co. Ltd. At The Weizmann Institute Of Science | Copolymer 1 related polypeptides for use as molecular weight markers and for therapeutic use |
AU775073C (en) | 1998-11-12 | 2007-05-03 | Yeda Research And Development Co. Ltd. | Pharmaceutical compositions comprising synthetic peptide copolymers and methods for preventing and treating GVHD and HVGD |
US6114649A (en) | 1999-07-13 | 2000-09-05 | Duran Technologies Inc. | Anode electrode for plasmatron structure |
EP1250450A2 (en) | 1999-09-03 | 2002-10-23 | University of Iowa Research Foundation Inc. | Quorum sensing signaling in bacteria |
DE19944003C1 (en) | 1999-09-14 | 2001-03-22 | Baumeister & Ostler Gmbh Co | Foldable separator |
ES2243450T3 (en) * | 2000-01-20 | 2005-12-01 | Yeda Research And Development Co. Ltd. | THE USE OF COPOLIMERO 1 AND PEPTIDES AND RELATED POLYPEPTIDES, AND OF T-CELLS TREATED WITH THE SAME, FOR NEUROPROTECTOR THERAPY. |
US7022663B2 (en) | 2000-02-18 | 2006-04-04 | Yeda Research And Development Co., Ltd. | Oral, nasal and pulmonary dosage formulations of copolymer 1 |
CA2400374A1 (en) | 2000-02-18 | 2001-08-23 | Adrian Gilbert | Oral, nasal and pulmonary dosage formualtions of copolymer 1 |
US20020077278A1 (en) | 2000-06-05 | 2002-06-20 | Yong V. Wee | Use of glatiramer acetate (copolymer 1) in the treatment of central nervous system disorders |
US20020037848A1 (en) | 2000-06-07 | 2002-03-28 | Michal Eisenbach-Schwartz | Use of copolymer 1 and related peptides and polypeptides and T cells treated therewith for neuroprotective therapy |
WO2002076503A1 (en) | 2000-06-20 | 2002-10-03 | Mayo Foundation For Medical Education And Research | Treatment of central nervous system diseases by antibodies against glatiramer acetate |
JP3698984B2 (en) | 2000-11-10 | 2005-09-21 | ヤマウチ株式会社 | Shoe press belt |
JP2004517074A (en) * | 2000-11-20 | 2004-06-10 | ファルマシア・コーポレーション | Substituted polycyclic aryl and heteroaryl pyridines useful for selectively inhibiting the coagulation cascade |
JP3661935B2 (en) | 2001-06-20 | 2005-06-22 | ソニー株式会社 | Information processing apparatus and method, recording medium, and program |
US7429374B2 (en) * | 2001-12-04 | 2008-09-30 | Teva Pharmaceutical Industries, Ltd. | Process for the measurement of the potency of glatiramer acetate |
AU2003301457A1 (en) | 2002-05-09 | 2004-05-04 | Keith Baumann | Bioweapon-detecting fibrous-network products and methods for making same |
CA2411786C (en) * | 2002-11-13 | 2009-01-27 | Brantford Chemicals Inc. | A process for the preparation of polypeptides from n-carboxyanhydrides of amino acids |
AU2003283152A1 (en) * | 2002-11-13 | 2004-06-03 | Apotex Pharmachem Inc. | Process for the preparation of glatiramer acetate by polymerisation of n-carboxy anhydrides of l-alanine, l-tyrosine, benzyl l-glutamate and benzyloxycarbonyl l-lysine |
DE10353960B4 (en) | 2003-10-16 | 2006-03-23 | Vertilas Gmbh | Surface-emitting semiconducting laser with structured waveguide has structured layer about lateral area of elevation with thickness selected so its optical thickness is at least equal to that of current carrying layer near elevation depth |
WO2006029411A2 (en) | 2004-09-09 | 2006-03-16 | Yeda Research And Development Co. Ltd. | Mixtures of polypeptides, compositions containing and processes for preparing same, and uses thereof |
NZ554018A (en) | 2004-09-09 | 2009-06-26 | Teva Pharma | Process for preparation of trifluoroacetyl glatiramer acetate using purified hydrobromic acid |
US20060172942A1 (en) | 2005-02-02 | 2006-08-03 | Teva Pharmaceutical Industries, Ltd. | Process for producing polypeptide mixtures using hydrogenolysis |
EP1891233A4 (en) * | 2005-04-25 | 2010-03-24 | Yeda Res & Dev | Markers associated with the therapeutic efficacy of glatiramer acetate |
WO2007072865A1 (en) | 2005-12-22 | 2007-06-28 | Pioneer Corporation | Facility information delivery device, communication terminal, facility information delivery method, information output method, program, and recording medium |
-
2005
- 2005-09-09 NZ NZ554018A patent/NZ554018A/en unknown
- 2005-09-09 AT AT05791236T patent/ATE454396T1/en active
- 2005-09-09 PT PT05791236T patent/PT1799703E/en unknown
- 2005-09-09 RS RS20140097A patent/RS53248B/en unknown
- 2005-09-09 EP EP10150124A patent/EP2177528B1/en not_active Revoked
- 2005-09-09 KR KR1020077007738A patent/KR101317131B1/en active IP Right Grant
- 2005-09-09 CA CA2579656A patent/CA2579656C/en active Active
- 2005-09-09 ES ES10150124T patent/ES2382298T3/en active Active
- 2005-09-09 DE DE602005018800T patent/DE602005018800D1/en active Active
- 2005-09-09 PL PL10194363T patent/PL2361924T3/en unknown
- 2005-09-09 UA UAA200703838A patent/UA91029C2/en unknown
- 2005-09-09 ES ES05791236T patent/ES2338138T3/en active Active
- 2005-09-09 CN CN200580033851.5A patent/CN101166754B/en active Active
- 2005-09-09 MX MX2007002760A patent/MX2007002760A/en active IP Right Grant
- 2005-09-09 PT PT10150124T patent/PT2177528E/en unknown
- 2005-09-09 EP EP10194363.7A patent/EP2361924B1/en not_active Revoked
- 2005-09-09 US US11/223,072 patent/US7495072B2/en active Active
- 2005-09-09 PL PL10150124T patent/PL2177528T3/en unknown
- 2005-09-09 JP JP2007531423A patent/JP5149008B2/en not_active Expired - Fee Related
- 2005-09-09 AU AU2005282249A patent/AU2005282249B2/en active Active
- 2005-09-09 DK DK10150124.5T patent/DK2177528T3/en active
- 2005-09-09 SI SI200531482T patent/SI2177528T1/en unknown
- 2005-09-09 RS RSP-2010/0114A patent/RS51257B/en unknown
- 2005-09-09 PL PL05791236T patent/PL1799703T3/en unknown
- 2005-09-09 SI SI200531830T patent/SI2361924T1/en unknown
- 2005-09-09 SI SI200530934T patent/SI1799703T1/en unknown
- 2005-09-09 BR BRPI0515033-7A patent/BRPI0515033B1/en not_active IP Right Cessation
- 2005-09-09 DK DK10194363.7T patent/DK2361924T3/en active
- 2005-09-09 RS RS20120091A patent/RS52265B/en unknown
- 2005-09-09 RU RU2007112956/04A patent/RU2388764C2/en active
- 2005-09-09 AT AT10150124T patent/ATE536363T1/en active
- 2005-09-09 EP EP05791236A patent/EP1799703B1/en not_active Revoked
- 2005-09-09 WO PCT/US2005/032395 patent/WO2006029393A2/en active Application Filing
- 2005-09-09 DK DK05791236.2T patent/DK1799703T3/en active
- 2005-09-09 ES ES10194363.7T patent/ES2451006T3/en active Active
- 2005-09-09 ZA ZA200702591A patent/ZA200702591B/en unknown
- 2005-09-09 PT PT101943637T patent/PT2361924E/en unknown
-
2006
- 2006-09-27 US US11/529,668 patent/US20070021324A1/en not_active Abandoned
-
2007
- 2007-02-27 IL IL181596A patent/IL181596A/en active IP Right Grant
- 2007-03-16 IS IS8622A patent/IS8622A/en unknown
- 2007-03-28 NO NO20071632A patent/NO20071632L/en not_active Application Discontinuation
- 2007-08-14 HK HK07108827.5A patent/HK1100780A1/en not_active IP Right Cessation
-
2010
- 2010-03-19 HR HR20100164T patent/HRP20100164T1/en unknown
- 2010-03-31 CY CY20101100308T patent/CY1110280T1/en unknown
- 2010-07-23 HK HK11110984.4A patent/HK1156637A1/en not_active IP Right Cessation
- 2010-07-23 HK HK10107102.8A patent/HK1140775A1/en not_active IP Right Cessation
-
2012
- 2012-03-02 HR HRP20120209TT patent/HRP20120209T1/en unknown
-
2014
- 2014-03-10 HR HRP20140216TT patent/HRP20140216T1/en unknown
-
2015
- 2015-09-17 IL IL241702A patent/IL241702A0/en unknown
Non-Patent Citations (1)
Title |
---|
See references of EP1799703A2 * |
Cited By (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009129018A1 (en) * | 2008-04-16 | 2009-10-22 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
EP2277050B2 (en) † | 2008-04-16 | 2022-09-28 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
US7884187B2 (en) | 2008-04-16 | 2011-02-08 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
US10160992B2 (en) | 2008-04-16 | 2018-12-25 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
US9410964B2 (en) | 2008-04-16 | 2016-08-09 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
US9395374B2 (en) | 2008-04-16 | 2016-07-19 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
US8329391B2 (en) | 2008-04-16 | 2012-12-11 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
US9085796B2 (en) | 2008-04-16 | 2015-07-21 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
US8592142B2 (en) | 2008-04-16 | 2013-11-26 | Momenta Pharmaceuticals, Inc. | Analysis of amino acid copolymer compositions |
US8859489B2 (en) | 2009-04-03 | 2014-10-14 | Momenta Pharmaceuticals, Inc. | Water-mediated control of depolymerization step of glatiramer acetate synthesis |
WO2010115175A1 (en) | 2009-04-03 | 2010-10-07 | Momenta Pharmaceticals, Inc. | Control of copolymer compositions |
US8058235B1 (en) | 2009-04-03 | 2011-11-15 | Momenta Pharmaceuticals, Inc. | Water-mediated control of depolymerization step of glatiramer acetate synthesis |
USRE49251E1 (en) | 2010-01-04 | 2022-10-18 | Mapi Pharma Ltd. | Depot systems comprising glatiramer or pharmacologically acceptable salt thereof |
EP2563804A4 (en) * | 2010-04-27 | 2014-09-17 | Reddys Lab Ltd Dr | Preparation of polypeptides and salts thereof |
EP2563804A2 (en) * | 2010-04-27 | 2013-03-06 | Dr. Reddy's Laboratories Ltd. | Preparation of polypeptides and salts thereof |
US9625473B2 (en) | 2010-10-11 | 2017-04-18 | Teva Pharmaceutical Industries Ltd. | Cytokine biomarkers as predictive biomarkers of clinical response for glatiramer acetate |
WO2012123959A2 (en) | 2011-02-14 | 2012-09-20 | Usv Limited | Copolymer-1, process for preparation and analytical methods thereof |
US8324348B1 (en) | 2011-07-11 | 2012-12-04 | Momenta Pharmaceuticals, Inc. | Evaluation of copolymer diethylamide |
US8765911B2 (en) | 2011-07-11 | 2014-07-01 | Momenta Pharmaceuticals, Inc. | Evaluation of copolymer diethylamide |
US8759484B2 (en) | 2011-07-11 | 2014-06-24 | Momenta Pharmaceuticals, Inc. | Evaluation of copolymer diethylamide |
US9617596B2 (en) | 2012-10-10 | 2017-04-11 | Teva Pharmaceutical Industries, Ltd. | Biomarkers predictive for clinical response for glatiramer acetate |
US9702007B2 (en) | 2013-10-21 | 2017-07-11 | Teva Pharmaceuticals Industries, Ltd. | Genetic markers predictive of response to glatiramer acetate |
EP3199544B1 (en) * | 2014-09-26 | 2021-11-17 | Hybio Pharmaceutical Co., Ltd | Preparation method for glatiramer acetate |
US9155775B1 (en) | 2015-01-28 | 2015-10-13 | Teva Pharmaceutical Industries, Ltd. | Process for manufacturing glatiramer acetate product |
US9763993B2 (en) | 2015-01-28 | 2017-09-19 | Teva Pharmaceutical Industries Ltd. | Process for manufacturing glatiramer acetate product |
US11167003B2 (en) | 2017-03-26 | 2021-11-09 | Mapi Pharma Ltd. | Methods for suppressing or alleviating primary or secondary progressive multiple sclerosis (PPMS or SPMS) using sustained release glatiramer depot systems |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP2177528B1 (en) | Process for the preparation of mixtures of trifluoroacetyl glatiramer acetate using purified hydrobromic acid | |
Scholtz et al. | The energetics of ion-pair and hydrogen-bonding interactions in a helical peptide | |
Taylor et al. | Epidermal growth factor: physical and chemical properties | |
US9029507B2 (en) | Copolymer-1, process for preparation and analytical methods thereof | |
CN103520735A (en) | Formulations of human growth hormone comprising a non-naturally encoded amino acid | |
Cuatrecasas et al. | Cross-linking of aminotyrosyl residues in the active site of staphylococcal nuclease | |
Mascioni et al. | Conformational preferences of the amylin nucleation site in SDS micelles: an NMR study | |
Strosberg et al. | Amino acid sequence of rabbit pneumococcal antibody. I. Light-chain cysteine-containing peptides | |
WO2002062833A2 (en) | Modified leptin with reduced immunogenicity | |
Hegyi et al. | Photoaffinity labeling of the nucleotide binding site of actin | |
CA2437272A1 (en) | Modified erythropoietin (epo) with reduced immunogenicity | |
EP1411969A1 (en) | Modified protamine with reduced immunogenicity | |
CA2439682A1 (en) | Modified ciliary neurotrophic factor (cntf) with reduced immunogenicity | |
Fredrickson et al. | Helix-coil stability constants for the naturally occurring amino acids in water. 19. Isoleucine parameters from random poly [(hydroxypropyl) glutamine-co-L-isoleucine] | |
Barden et al. | Fluorine-19 NMR study of the myosin and tropomyosin binding sites on actin | |
Nakamura et al. | JAL-TA9 inhibits aggregation of hPrP180-192 through the cleavage reaction | |
Chin | Calmodulin: The relationship between structure and function explored by trace chemical modification and molecular modeling | |
JP2003501017A (en) | Regulation of gene expression in gastrointestinal inflammation | |
AU2002242715A1 (en) | Modified protamine with reduced immunogenicity | |
AU2002250891A1 (en) | Modified leptin with reduced immunogenicity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200580033851.5 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU LV MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 181596 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/a/2007/002760 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007531423 Country of ref document: JP Ref document number: 2579656 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 554018 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2234/DELNP/2007 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005282249 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020077007738 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007112956 Country of ref document: RU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005791236 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2005282249 Country of ref document: AU Date of ref document: 20050909 Kind code of ref document: A |
|
WWP | Wipo information: published in national office |
Ref document number: 2005282249 Country of ref document: AU |
|
WWP | Wipo information: published in national office |
Ref document number: 2005791236 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: PI0515033 Country of ref document: BR |
|
WWE | Wipo information: entry into national phase |
Ref document number: P-2010/0114 Country of ref document: RS |
|
WWE | Wipo information: entry into national phase |
Ref document number: 241702 Country of ref document: IL |