title: Production of peptides as generic drugs: a patent landscape of octreotide.
abstract: BACKGROUND
  New low-cost strategies and enhancement of the already described methods to manufacture peptide molecules on an industrial scale are highly requested, particularly for peptides such as octreotide, which, along with goserelin and leuprolide, dominate the global peptide market. A number of patents related to the production of octreotide can be found, concerning both solution and solid-phase synthesis. Thus, there is a need to revise the existing synthetic approaches in order to organize them in a more comprehensible way.
  
  
  METHODS
  The octreotide patent landscape could help improvement of the methods for manufacturing of octreotide in industrial scale, leading to the appearance of innovative approaches.
  
  
  CONCLUSIONS
  The pharmaceutical value of octreotide can be seen from its high market percentage among other peptide drugs. The complex chemical structure of octreotide represents the main challenge for its industrial production. Two synthetic steps are crucial in the preparation of octreotide: (i) threoninol attachment or on resin formation working in solid-phase and (ii) disulphide bond formation to achieve cyclic structure. Analysis of various patents filed to date allows us to see the trend in simplification of the synthetic approaches from the labor intensive syntheses in solution to the more versatile and rapid solid-phase methods.
authors.affiliation: a Laboratory of Peptide and Protein Chemistry and Biology - PeptLab , Sesto Fiorentino (Florence) , Italy.|b Department of Chemistry 'Ugo Schiff' , University of Florence , Sesto Fiorentino (Florence) , Italy.|c Espikem Srl , Prato , Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sabatino
authors.affiliation: d Fresenius Kabi Anti Infectives Srl , Milano , Italy.|e Institute of Chemistry , St. Petersburg State University , St. Petersburg , Russia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Guryanov
authors.affiliation: f Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmaceutical Sciences and Nutraceutics , University of Florence , Sesto Fiorentino , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rombecchi
authors.affiliation: d Fresenius Kabi Anti Infectives Srl , Milano , Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Zanon
authors.affiliation: d Fresenius Kabi Anti Infectives Srl , Milano , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ricci
authors.affiliation: d Fresenius Kabi Anti Infectives Srl , Milano , Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
authors.affiliation: a Laboratory of Peptide and Protein Chemistry and Biology - PeptLab , Sesto Fiorentino (Florence) , Italy.|b Department of Chemistry 'Ugo Schiff' , University of Florence , Sesto Fiorentino (Florence) , Italy.|g PeptLab@UCP Platform and Laboratory of Chemical Biology EA4505 , University of Cergy-Pontoise , Cergy-Pontoise CEDEX , France.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Papini
authors.affiliation: a Laboratory of Peptide and Protein Chemistry and Biology - PeptLab , Sesto Fiorentino (Florence) , Italy.|f Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmaceutical Sciences and Nutraceutics , University of Florence , Sesto Fiorentino , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rovero
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D004345:Drug Industry / Q000379:methods; D016568:Drugs, Generic / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D015282:Octreotide / Q000138:chemical synthesis* / Q000737:chemistry; D010330:Patents as Topic; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D016568:Drugs, Generic; D010455:Peptides; D015282:Octreotide
keywords: Octreotide; peptides manufacturing; solution and solid-phase methods; somatotropin release-inhibiting factor (SRIF)