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Glatiramer acetate

January 01, 1970

Glatiramer acetate (also known as Copolymer 1, Cop-1), sold under the brand name Copaxone among others, is an immunomodulator medication used to treat multiple sclerosis.[1][2] Glatiramer acetate is approved in the United States to reduce the frequency of relapses, but not for reducing the progression of disability. Observational studies, but not randomized controlled trials, suggest that it may reduce progression of disability. While a conclusive diagnosis of multiple sclerosis requires a history of two or more episodes of symptoms and signs, glatiramer acetate is approved to treat a first episode anticipating a diagnosis. It is also used to treat relapsing-remitting multiple sclerosis. It is administered by subcutaneous injection.[1][2]

Glatiramer acetate
Clinical data
Trade namesCopaxone,[1] Glatopa,[2] Brabio
AHFS/Drugs.comMonograph
MedlinePlusa603016
License data
Pregnancy
category
  • AU: B1
Routes of
administration		Subcutaneous injection
ATC code
Legal status
Legal status
Identifiers
CAS Number
  • 147245-92-9 Y
PubChem CID
  • 3081884
DrugBank
  • DB05259 N
ChemSpider
  • none
UNII
  • 5M691HL4BO
ChEMBL
  • ChEMBL1201507 N
CompTox Dashboard (EPA)
  • DTXSID30163637
ECHA InfoCard100.248.824
Chemical and physical data
FormulaC25H45N5O13
Molar mass623.657 g·mol−1
 NY (what is this?)  (verify)

It is a mixture of random-sized peptides that are composed of the four amino acids found in myelin basic protein, namely glutamic acid, lysine, alanine, and tyrosine. Myelin basic protein is the antigen in the myelin sheaths of the neurons that stimulates an autoimmune reaction in people with MS, so the peptide may work as a decoy for the attacking immune cells.

It is on the World Health Organization's List of Essential Medicines.[6]

History edit

Glatiramer acetate was originally discovered at the Weizmann Institute of Science. Three main clinical trials followed to demonstrate safety and efficacy: The first trial was performed in a single center, double-blind, placebo controlled trial and included 50 patients.[7] The second trial was a two-year, multi-center, randomized, double-blind, placebo controlled trial and involved 251 patients.[8] The third trial was a double-blind MRI study involving participation of 239 patients.[9]

Medical uses edit

Glatiramer acetate is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.[1]

A 2010 Cochrane review concluded that glatiramer acetate had partial efficacy in "relapse-related clinical outcomes" but no effect on progression of the disease.[10] As a result, it is approved by the FDA for reducing the frequency of relapses, but not for reducing the progression of disability.[1][2]

A 15-year followup of the original trial compared patients who continued with glatiramer to patients who dropped out of the trial. Patients with glatiramer had reduced relapse rates, and decreased disability progression and transition to secondary progressive MS, compared to patients who did not continue glatiramer. However, the two groups were not necessarily comparable, as it was no longer a randomized trial. There were no long-term safety issues.[11]

Adverse effects edit

 
An injection site reaction on the upper left arm

Side effects may include a lump at the injection site (injection site reaction) in approximately 30% of users, and aches, fever, chills (flu-like symptoms) in approximately 10% of users.[12] Side effect symptoms are generally mild in nature. A reaction that involves flushing, shortness of breath, anxiety and rapid heartbeat has been reported soon after injection in up to 5% of patients (usually after inadvertently injecting directly into a vein). These side effects subside within thirty minutes. Over time, a visible dent at a repeat-injection site can occur due to the local destruction of fat tissue, known as lipoatrophy, that may develop.

More serious side effects have been reported for glatiramer acetate, according to the FDA's prescribing label, these include serious side effects to the cardiovascular, digestive (including the liver), hematopoietic, lymphatic, musculoskeletal, nervous, respiratory, and urogenital systems as well as special senses (in particular the eyes). Metabolic and nutritional disorders have also been reported; however a link between glatiramer acetate and these adverse effects has not been established.[1][2]

It may also cause Jessner lymphocytic infiltrate.[13]

Mechanism of action edit

Glatiramer acetate is a random polymer (average molecular mass 6.4 kD) composed of four amino acids found in myelin basic protein. The mechanism of action for glatiramer acetate is not fully elucidated. It is thought to act by modifying immune processes that are believed to be responsible for the pathogenesis of MS. Administration of glatiramer acetate shifts the population of T cells from proinflammatory Th1 T-cells to regulatory Th2 T-cells that suppress the inflammatory response.[14] This is done by the inhibition of secretion of proinflammatory cytokines (IL-1, IL-12, TNF, INFγ) by Th1 T-cells, thereby inducing Th2 T-cells to cross the blood–brain barrier and produce anti-inflammatory cytokines (IL-4, IL-5, IL-13, IL-10, TGF-β).[15] Given its resemblance to myelin basic protein, glatiramer acetate may act as a decoy, diverting an autoimmune response against myelin. This hypothesis is supported by findings of studies that have been carried out to explore the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a condition induced in several animal species through immunization against central nervous system derived material containing myelin and often used as an experimental animal model of MS. Studies in animals and in vitro systems suggest that upon its administration, glatiramer acetate-specific regulatory T cells (Tregs) are induced and activated in the periphery, inhibiting the inflammatory reaction to myelin basic protein.[1][2]

The integrity of the blood–brain barrier, however, is not appreciably affected by glatiramer acetate, at least not in the early stages of treatment. Glatiramer acetate has been shown in clinical trials to reduce the number and severity of multiple sclerosis exacerbations.[16]

Society and culture edit

Marketing edit

Glatiramer acetate has been approved for marketing in numerous countries worldwide, including the United States, Israel, Canada and 24 European Union countries.[17][18] Approval in the U.S. was obtained in 1997.[19] Glatiramer acetate was approved for marketing in the U.K. in August 2000, and launched in December.[20] This first approval in a major European market led to approval across the European Union under the mutual recognition procedure. Iran is proceeding with domestic manufacture of glatiramer acetate.[21][22]

Patent status edit

Novartis subsidiary Sandoz has marketed Glatopa since 2015, a generic version of the original Teva 20 mg formulation that requires daily injection.[23]

Teva developed a long-acting 40 mg formulation, marketed since 2015, which reduced required injections to three per week.[24] In October 2017, the FDA approved a generic version, which is manufactured in India by Natco Pharma, and imported and sold by Dutch firm Mylan.[25][26] In February 2018, Sandoz received FDA approval for their generic version.[27] In parallel with the development and approval processes, the generic competitors have disputed Teva's newer patents, any of which if upheld, would prevent marketing of long-acting generics.[28]

While the patent on the chemical drug expired in 2015,[29] Teva obtained new US patents covering pharmaceutical formulations for long-acting delivery.[30] Litigation from industry competitors in 2016-2017 resulted in the new patents being judged invalid.[31][32] In October 2018, the U.S. Court of Appeals for the Federal Circuit upheld the patent invalidation for obviousness.[33][34] The case reflects the larger controversy over evergreening of generic drugs.

References edit

  1. ^ a b c d e f g h "Copaxone- glatiramer acetate injection, solution". DailyMed. 23 July 2020. Retrieved 11 November 2020.
  2. ^ a b c d e f g "Glatopa- glatiramer acetate injection, solution". DailyMed. 31 July 2020. Retrieved 11 November 2020.
  3. ^ "Neurological therapies". Health Canada. 9 May 2018. Retrieved 13 April 2024.
  4. ^ "Brabio 20 mg/mL Solution for Injection, Pre-filled Syringe - Summary of Product Characteristics (SmPC)". (emc). Retrieved 11 November 2020.
  5. ^ "Copaxone 20 mg/ml solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC)". (emc). 29 September 2020. Retrieved 11 November 2020.
  6. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  7. ^ Bornstein MB, Miller A, Slagle S, Weitzman M, Crystal H, Drexler E, Keilson M, Merriam A, Wassertheil-Smoller S, Spada V (August 1987). "A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis". The New England Journal of Medicine. 317 (7): 408–14. doi:10.1056/NEJM198708133170703. PMID 3302705.
  8. ^ Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB (July 1995). "Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group". Neurology. 45 (7): 1268–76. doi:10.1212/WNL.45.7.1268. PMID 7617181. S2CID 28895177.
  9. ^ Comi G, Filippi M, Wolinsky JS (March 2001). "European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging--measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group". Annals of Neurology. 49 (3): 290–7. doi:10.1002/ana.64. PMID 11261502. S2CID 35614752.
  10. ^ La Mantia L, Munari LM, Lovati R (May 2010). "Glatiramer acetate for multiple sclerosis". The Cochrane Database of Systematic Reviews. 5 (5): CD004678. doi:10.1002/14651858.CD004678.pub2. PMID 20464733.
  11. ^ Ford C, Goodman AD, Johnson K, Kachuck N, Lindsey JW, Lisak R, et al. (March 2010). "Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate". Multiple Sclerosis. 16 (3): 342–50. doi:10.1177/1352458509358088. PMC 2850588. PMID 20106943.
  12. ^ "Copaxone". MediGuard.
  13. ^ Krafchik BR (2011). "Reaction Patterns". In Schachner LA, Hansen RC (eds.). Pediatric Dermatology. Elsevier Health Sciences. p. 1022. ISBN 978-0-7234-3665-2.
  14. ^ Arnon R, Sela M (1999). (PDF). Chem. Israel. 1: 12–17. Archived from the original (PDF) on 2003-09-07.
  15. ^ https://go.drugbank.com/drugs/DB05259; Glatiramer Mechanism of Action
  16. ^ "Copaxone". All About Multiple Sclerosis.
  17. ^ McKeage K (May 2015). "Glatiramer Acetate 40 mg/mL in Relapsing-Remitting Multiple Sclerosis: A Review". CNS Drugs. 29 (5): 425–32. doi:10.1007/s40263-015-0245-z. PMID 25906331. S2CID 30186027.
  18. ^ Comi G, Amato MP, Bertolotto A, Centonze D, De Stefano N, Farina C, et al. (2016). "The heritage of glatiramer acetate and its use in multiple sclerosis". Multiple Sclerosis and Demyelinating Disorders. 1 (1). doi:10.1186/s40893-016-0010-2.
  19. ^ "Copaxone". CenterWatch.
  20. ^ "Teva's Copaxone approved in UK". The Pharma Letter.
  21. ^ . Tofigh Daru Research and Engineering Company. Archived from the original on 2018-10-21. Retrieved 2017-02-01.
  22. ^ Isayev S, Jafarov T (1 May 2012). "Iran to manufacture multiple sclerosis cure". Trend News Agency.
  23. ^ . Novartis. 2015. Archived from the original on 2018-02-03. Retrieved 2017-02-21.
  24. ^ Silva P (9 October 2015). "New 3-Times-Per-Week Regimen For Teva's Copaxone". Multiple Sclerosis News Today.
  25. ^ Erman M, Grover D (3 October 2017). "Mylan surges, Teva slumps after FDA okays Copaxone copy". Reuters. Retrieved 4 October 2017.
  26. ^ . NATCO Pharma (India). 3 October 2017. Archived from the original on 10 January 2019. Retrieved 4 October 2017.>
  27. ^ "Sandoz announces US FDA approval and launch of Glatopa 40 mg/mL". Novartis International AG. February 13, 2018. Retrieved May 10, 2018.
  28. ^ "Teva's Copaxone still growing despite patent risks". BioPharmaDive.
  29. ^ Helfand C. "Copaxone". FiercePharma.
  30. ^ Decker S (1 September 2016). "Teva loses decision on validity of 302 copaxone patent". Bloomberg Markets.
  31. ^ Decker S, Flanagan C, Benmeleh Y (30 January 2017). "Teva loses ruling invalidating patents on copaxone drug". Bloomberg Markets.
  32. ^ "Teva loses patent ruling". Briefcase. The Philadelphia Inquirer. Bloomberg News. September 2, 2017. p. A12. Retrieved June 23, 2018 – via Newspapers.com (Publisher Extra).
  33. ^ "U.S. appeals court upholds ruling that canceled Teva Copaxone patents". Reuters. October 12, 2018. Retrieved October 12, 2018.
  34. ^ "In Re: Copaxone Consolidated Cases" (PDF). United States Court of Appeals for the Federal Circuit. October 12, 2018. Retrieved October 12, 2018.

January 01, 1970
glatiramer, acetate, also, known, copolymer, sold, under, brand, name, copaxone, among, others, immunomodulator, medication, used, treat, multiple, sclerosis, approved, united, states, reduce, frequency, relapses, reducing, progression, disability, observation. Glatiramer acetate also known as Copolymer 1 Cop 1 sold under the brand name Copaxone among others is an immunomodulator medication used to treat multiple sclerosis 1 2 Glatiramer acetate is approved in the United States to reduce the frequency of relapses but not for reducing the progression of disability Observational studies but not randomized controlled trials suggest that it may reduce progression of disability While a conclusive diagnosis of multiple sclerosis requires a history of two or more episodes of symptoms and signs glatiramer acetate is approved to treat a first episode anticipating a diagnosis It is also used to treat relapsing remitting multiple sclerosis It is administered by subcutaneous injection 1 2 Glatiramer acetateClinical dataTrade namesCopaxone 1 Glatopa 2 BrabioAHFS Drugs comMonographMedlinePlusa603016License dataUS DailyMed GlatiramerPregnancycategoryAU B1Routes ofadministrationSubcutaneous injectionATC codeL03AX13 WHO Legal statusLegal statusAU S4 Prescription only CA only 3 UK POM Prescription only 4 5 US only 1 2 IdentifiersCAS Number147245 92 9 YPubChem CID3081884DrugBankDB05259 NChemSpidernoneUNII5M691HL4BOChEMBLChEMBL1201507 NCompTox Dashboard EPA DTXSID30163637ECHA InfoCard100 248 824Chemical and physical dataFormulaC 25H 45N 5O 13Molar mass623 657 g mol 1 N Y what is this verify It is a mixture of random sized peptides that are composed of the four amino acids found in myelin basic protein namely glutamic acid lysine alanine and tyrosine Myelin basic protein is the antigen in the myelin sheaths of the neurons that stimulates an autoimmune reaction in people with MS so the peptide may work as a decoy for the attacking immune cells It is on the World Health Organization s List of Essential Medicines 6 Contents 1 History 2 Medical uses 3 Adverse effects 4 Mechanism of action 5 Society and culture 5 1 Marketing 5 2 Patent status 6 ReferencesHistory editGlatiramer acetate was originally discovered at the Weizmann Institute of Science Three main clinical trials followed to demonstrate safety and efficacy The first trial was performed in a single center double blind placebo controlled trial and included 50 patients 7 The second trial was a two year multi center randomized double blind placebo controlled trial and involved 251 patients 8 The third trial was a double blind MRI study involving participation of 239 patients 9 Medical uses editGlatiramer acetate is indicated for the treatment of relapsing forms of multiple sclerosis MS to include clinically isolated syndrome relapsing remitting disease and active secondary progressive disease in adults 1 A 2010 Cochrane review concluded that glatiramer acetate had partial efficacy in relapse related clinical outcomes but no effect on progression of the disease 10 As a result it is approved by the FDA for reducing the frequency of relapses but not for reducing the progression of disability 1 2 A 15 year followup of the original trial compared patients who continued with glatiramer to patients who dropped out of the trial Patients with glatiramer had reduced relapse rates and decreased disability progression and transition to secondary progressive MS compared to patients who did not continue glatiramer However the two groups were not necessarily comparable as it was no longer a randomized trial There were no long term safety issues 11 Adverse effects edit nbsp An injection site reaction on the upper left arm Side effects may include a lump at the injection site injection site reaction in approximately 30 of users and aches fever chills flu like symptoms in approximately 10 of users 12 Side effect symptoms are generally mild in nature A reaction that involves flushing shortness of breath anxiety and rapid heartbeat has been reported soon after injection in up to 5 of patients usually after inadvertently injecting directly into a vein These side effects subside within thirty minutes Over time a visible dent at a repeat injection site can occur due to the local destruction of fat tissue known as lipoatrophy that may develop More serious side effects have been reported for glatiramer acetate according to the FDA s prescribing label these include serious side effects to the cardiovascular digestive including the liver hematopoietic lymphatic musculoskeletal nervous respiratory and urogenital systems as well as special senses in particular the eyes Metabolic and nutritional disorders have also been reported however a link between glatiramer acetate and these adverse effects has not been established 1 2 It may also cause Jessner lymphocytic infiltrate 13 Mechanism of action editGlatiramer acetate is a random polymer average molecular mass 6 4 kD composed of four amino acids found in myelin basic protein The mechanism of action for glatiramer acetate is not fully elucidated It is thought to act by modifying immune processes that are believed to be responsible for the pathogenesis of MS Administration of glatiramer acetate shifts the population of T cells from proinflammatory Th1 T cells to regulatory Th2 T cells that suppress the inflammatory response 14 This is done by the inhibition of secretion of proinflammatory cytokines IL 1 IL 12 TNF INFg by Th1 T cells thereby inducing Th2 T cells to cross the blood brain barrier and produce anti inflammatory cytokines IL 4 IL 5 IL 13 IL 10 TGF b 15 Given its resemblance to myelin basic protein glatiramer acetate may act as a decoy diverting an autoimmune response against myelin This hypothesis is supported by findings of studies that have been carried out to explore the pathogenesis of experimental autoimmune encephalomyelitis EAE a condition induced in several animal species through immunization against central nervous system derived material containing myelin and often used as an experimental animal model of MS Studies in animals and in vitro systems suggest that upon its administration glatiramer acetate specific regulatory T cells Tregs are induced and activated in the periphery inhibiting the inflammatory reaction to myelin basic protein 1 2 The integrity of the blood brain barrier however is not appreciably affected by glatiramer acetate at least not in the early stages of treatment Glatiramer acetate has been shown in clinical trials to reduce the number and severity of multiple sclerosis exacerbations 16 Society and culture editMarketing edit Glatiramer acetate has been approved for marketing in numerous countries worldwide including the United States Israel Canada and 24 European Union countries 17 18 Approval in the U S was obtained in 1997 19 Glatiramer acetate was approved for marketing in the U K in August 2000 and launched in December 20 This first approval in a major European market led to approval across the European Union under the mutual recognition procedure Iran is proceeding with domestic manufacture of glatiramer acetate 21 22 Patent status edit Novartis subsidiary Sandoz has marketed Glatopa since 2015 a generic version of the original Teva 20 mg formulation that requires daily injection 23 Teva developed a long acting 40 mg formulation marketed since 2015 which reduced required injections to three per week 24 In October 2017 the FDA approved a generic version which is manufactured in India by Natco Pharma and imported and sold by Dutch firm Mylan 25 26 In February 2018 Sandoz received FDA approval for their generic version 27 In parallel with the development and approval processes the generic competitors have disputed Teva s newer patents any of which if upheld would prevent marketing of long acting generics 28 While the patent on the chemical drug expired in 2015 29 Teva obtained new US patents covering pharmaceutical formulations for long acting delivery 30 Litigation from industry competitors in 2016 2017 resulted in the new patents being judged invalid 31 32 In October 2018 the U S Court of Appeals for the Federal Circuit upheld the patent invalidation for obviousness 33 34 The case reflects the larger controversy over evergreening of generic drugs References edit a b c d e f g h Copaxone glatiramer acetate injection solution DailyMed 23 July 2020 Retrieved 11 November 2020 a b c d e f g Glatopa glatiramer acetate injection solution DailyMed 31 July 2020 Retrieved 11 November 2020 Neurological therapies Health Canada 9 May 2018 Retrieved 13 April 2024 Brabio 20 mg mL Solution for Injection Pre filled Syringe Summary of Product Characteristics SmPC emc Retrieved 11 November 2020 Copaxone 20 mg ml solution for injection in pre filled syringe Summary of Product Characteristics SmPC emc 29 September 2020 Retrieved 11 November 2020 World Health Organization 2023 The selection and use of essential medicines 2023 web annex A World Health Organization model list of essential medicines 23rd list 2023 Geneva World Health Organization hdl 10665 371090 WHO MHP HPS EML 2023 02 Bornstein MB Miller A Slagle S Weitzman M Crystal H Drexler E Keilson M Merriam A Wassertheil Smoller S Spada V August 1987 A pilot trial of Cop 1 in exacerbating remitting multiple sclerosis The New England Journal of Medicine 317 7 408 14 doi 10 1056 NEJM198708133170703 PMID 3302705 Johnson KP Brooks BR Cohen JA Ford CC Goldstein J Lisak RP Myers LW Panitch HS Rose JW Schiffer RB July 1995 Copolymer 1 reduces relapse rate and improves disability in relapsing remitting multiple sclerosis results of a phase III multicenter double blind placebo controlled trial The Copolymer 1 Multiple Sclerosis Study Group Neurology 45 7 1268 76 doi 10 1212 WNL 45 7 1268 PMID 7617181 S2CID 28895177 Comi G Filippi M Wolinsky JS March 2001 European Canadian multicenter double blind randomized placebo controlled study of the effects of glatiramer acetate on magnetic resonance imaging measured disease activity and burden in patients with relapsing multiple sclerosis European Canadian Glatiramer Acetate Study Group Annals of Neurology 49 3 290 7 doi 10 1002 ana 64 PMID 11261502 S2CID 35614752 La Mantia L Munari LM Lovati R May 2010 Glatiramer acetate for multiple sclerosis The Cochrane Database of Systematic Reviews 5 5 CD004678 doi 10 1002 14651858 CD004678 pub2 PMID 20464733 Ford C Goodman AD Johnson K Kachuck N Lindsey JW Lisak R et al March 2010 Continuous long term immunomodulatory therapy in relapsing multiple sclerosis results from the 15 year analysis of the US prospective open label study of glatiramer acetate Multiple Sclerosis 16 3 342 50 doi 10 1177 1352458509358088 PMC 2850588 PMID 20106943 Copaxone MediGuard Krafchik BR 2011 Reaction Patterns In Schachner LA Hansen RC eds Pediatric Dermatology Elsevier Health Sciences p 1022 ISBN 978 0 7234 3665 2 Arnon R Sela M 1999 The chemistry of the Copaxone drug PDF Chem Israel 1 12 17 Archived from the original PDF on 2003 09 07 https go drugbank com drugs DB05259 Glatiramer Mechanism of Action Copaxone All About Multiple Sclerosis McKeage K May 2015 Glatiramer Acetate 40 mg mL in Relapsing Remitting Multiple Sclerosis A Review CNS Drugs 29 5 425 32 doi 10 1007 s40263 015 0245 z PMID 25906331 S2CID 30186027 Comi G Amato MP Bertolotto A Centonze D De Stefano N Farina C et al 2016 The heritage of glatiramer acetate and its use in multiple sclerosis Multiple Sclerosis and Demyelinating Disorders 1 1 doi 10 1186 s40893 016 0010 2 Copaxone CenterWatch Teva s Copaxone approved in UK The Pharma Letter Glatiramer Acetate Tofigh Daru Research and Engineering Company Archived from the original on 2018 10 21 Retrieved 2017 02 01 Isayev S Jafarov T 1 May 2012 Iran to manufacture multiple sclerosis cure Trend News Agency Sandoz announces US launch of Glatopa Novartis 2015 Archived from the original on 2018 02 03 Retrieved 2017 02 21 Silva P 9 October 2015 New 3 Times Per Week Regimen For Teva s Copaxone Multiple Sclerosis News Today Erman M Grover D 3 October 2017 Mylan surges Teva slumps after FDA okays Copaxone copy Reuters Retrieved 4 October 2017 NATCO s marketing partner Mylan receives final approval of generic glatiramer acetate for both 20 mg mL and 40 mg mL versions NATCO Pharma India 3 October 2017 Archived from the original on 10 January 2019 Retrieved 4 October 2017 gt Sandoz announces US FDA approval and launch of Glatopa 40 mg mL Novartis International AG February 13 2018 Retrieved May 10 2018 Teva s Copaxone still growing despite patent risks BioPharmaDive Helfand C Copaxone FiercePharma Decker S 1 September 2016 Teva loses decision on validity of 302 copaxone patent Bloomberg Markets Decker S Flanagan C Benmeleh Y 30 January 2017 Teva loses ruling invalidating patents on copaxone drug Bloomberg Markets Teva loses patent ruling Briefcase The Philadelphia Inquirer Bloomberg News September 2 2017 p A12 Retrieved June 23 2018 via Newspapers com Publisher Extra U S appeals court upholds ruling that canceled Teva Copaxone patents Reuters October 12 2018 Retrieved October 12 2018 In Re Copaxone Consolidated Cases PDF United States Court of Appeals for the Federal Circuit October 12 2018 Retrieved October 12 2018 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Glatiramer acetate amp oldid 1218836594, wikipedia, wiki, book, books, library,

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