agentes terapeuticos biotecnologia

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Principais Agentes Terapêuticos produzidos por microrganismos
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Proteínas humanas aprovadas para uso terapêutico ($60 billion-2006)
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Table 10.1
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Recombinant proteins-from http://en.wikipedia.org/wiki/List_of_recombinant_proteins -9/10/12
Human recombinants that largely replaced animal or harvested from human types
Human growth hormone (rhGH) Humatrope from Lilly and Serostim from Serono replaced cadaver harvested human growth hormone
Human insulin (rhI) Humulin from Lilly and Novolin from Novo Nordisk among others; largely replaced bovine and porcine insulin for human therapy. Some prefer to continue using the animal-sourced preparations, as there is some evidence that synthetic insulin varieties are more likely to induce hypoglycemia unawareness. Remaining manufacturers of highly-purified animal-sourced insulin include the U.K.'s Wockhardt Ltd. (headquartered in India), Poland's Polfa Tarchomin S.A., Argentina's Laboratorios Beta S.A., and China's Wanbang Biopharma Co.
Follicle-stimulating hormone FSH replaced Serono's Pergonal which was previously isolated from post-menopausal female urine
Factor VIII Kogenate from Bayer replaced blood harvested factor VIII
Human recombinants with recombination as only source
Erythropoietin (EPO) Epogen from Amgen
Granulocyte colony-stimulating factor (G-CSF) filgrastim sold as Neupogen from Amgen; pegfilgrastim sold as Neulasta
alpha-galactosidase A Fabrazyme by Genzyme
alpha-L-iduronidase (rhIDU; laronidase) Aldurazyme by BioMarin Pharmaceutical and Genzyme
N-acetylgalactosamine-4-sulfatase (rhASB; galsulfase) Naglazyme (TM) by BioMarin Pharmaceutical
DNAse Pulmozyme by Genentech
Tissue plasminogen activator (TPA) Activase by Genentech
Glucocerebrosidase Ceredase by Genzyme
Interferon (IF) Interferon-beta-1a as Avonex from Biogen Idec; Rebif from Serono; Interferon beta-1b as Betaseron from Schering
Insulin-like growth factor 1 (IGF-1)
Animal recombinants
Bovine somatotropin (bST)
Porcine somatotropin (pST)
Bovine Chymosin
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Interferon
Natural
Interferons
Man Made
Interferons
(Recombinant)
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Interferon
Envolvido com a 1ª linha de defesa contra infecções virais
Compõe o sistema imune inato-inespecífico
Produzido por células-estímulos
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Types on Interferon
Alfa (leukocyte interferon)
Leucócitos infectados por vírus
beta (fibroblast interferon)
Células epiteliais ou fibroblastos
gamma (immune interferon)
Linfócitos T ou NK 
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How Does It Prevent Viral Replication?
virus
cells
(Other stimuli:
exogenous ds RNA,
LPS, bacterial 
components)
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How Does It Prevent Viral Replication? 
virus
interferon
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How Does it Prevent Viral Replication?
virus
Inhibitory
proteins
No replication
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Interferon Response to Acute Viral Infection
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Effects of Interferon Treatment
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Mecanismo de Ação
IFN alpha and beta
Indução de inibidores de síntese de proteínas 
IFN gamma
Indução de moléculas de MHC II de APC
Indução de macrófagos resistirem a infecção e fagocitar células infectadas
All IFN
Indução de moléculas de MHC I
Indução de células NK
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Viral Defense Against Interferon
block interferon binding to cells
inhibit action of interferon-induced protein kinase
inhibit NK function
interfere with cell surface expression MHC
block complement activation
prevent apoptosis in host cell
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Indications for Interferon
alpha
Hepatitis B & C, Hairy cell leukemia, Chronic myeloid leukemia, multiple myeloma, low grade lymphomas, Kaposi’s Sarcoma, Melanoma
beta
Multiple Sclerosis, (Ulcerative colitis)
gamma
Chronic granulomatous disease, Chronic Myeloid Leukemia, Renal cell Carcinoma
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Incomplete List of Interferons
Actimmune
Alferon
Avonex
Betaserone
Infergen
Intron
Wellferon, etc
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Interferon Side Effects
Flu-like symptoms
Headache
Nausea, vomiting, diarrhea
Depression, irritability, anxiety
Injection site reactions, partial alopecia
Hematologic abnormalities
Autoimmune disorders
(Hepatitis C Data)
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Pegylated Interferon
HCV is an ideal setting for peginterferon
polyethylene glycol (PEG):interferon
Pegylation was developed to overcome disadvantages of standard interferon
shields IFN from enzymatic degradation thus lowers systemic clearance
allows less frequent dosing
achieve higher/sustained serum [interferon]
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Different Interferon Drugs
 Interferons are broken down into recombinant versions of a specific interferon subtype and purified blends of natural human interferon. 
 Many of these are in clinical use and are given intramuscularly or subcutaneously
 Recombinant forms of alpha interferon include:
Alpha-2a drug name Roferon
Alpha-2b drug name Intron A
Alpha-n1 drug name Wellferon
Alpha-n3 drug name AlferonN
Alpha-con1 drug name Infergen
Recombinant forms of beta interferon include:
Beta-1a drug name Avonex
Beta-1b drug name Betaseron
Recombinant forms of gamma interferon include:
Gamma-1b drug name Acimmune
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Anticorpos monoclonais aprovados para uso terapêutico
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Table 10.3
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Antibody Structure
Antibodies are immune system-related proteins called immunoglobulins. Each antibody consists of four polypeptides– two heavy chains and two light chains joined to form a "Y" shaped molecule.
 
The amino acid sequence in the tips of the "Y" varies greatly among different antibodies. This variable region, composed of 110-130 amino acids, give the antibody its specificity for binding antigen. The variable region includes the ends of the light and heavy chains. Treating the antibody with a protease can cleave this region, producing Fab or fragment antigen binding that include the variable ends of an antibody.
The constant region determines the mechanism used to destroy antigen. Antibodies are divided into five major classes, IgM, IgG, IgA, IgD, and IgE, based on their constant region structure and immune function. 
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Figure 10.24
Structure of an antibody molecule
Complementarity-determining regions (CDRs) 
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Figure 10.25
Genetically engineered chimeric antibody
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Figure 10.26
Genetically engineered humanized antibody
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Figure 10.40
Making monoclonal antibodies even more effective therapeutic agents: two ways
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