Biopharmaceuticals II

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Biopharmaceuticals II

• Core 218
• Spring 2007

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Biotherapeutic Agents

• Virtually all biotherapeutic agents in clinical
  use are biotech pharmaceuticals
• A biotech pharmaceutical is simply any medically
  useful drug whose manufacture involves
  microorganisms or substances that living
  organisms produce (e.g., enzymes).
• Most biotech pharmaceuticals are recombinantthat
  is, produced by genetic engineering

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Birth of Genentech

• Genentech was formed in 1976 by who?

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Genentech

• What was the first biopharmaceutical?
• Insulin

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Why was insulin a good choice?

• There is a need.
• In 1970 there were 7.5 million Americans using
  insulin and even more undiagnosed.
• Insulin produced from cattle and pigs was not an
  exact match for human insulin resulting in some
  adverse reactions.

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Genentech the Pioneers

• Initially faced skepticism from academic and
  business communities, however..
• 1977, produced first human protein (somatostatin,
  HGH inhibitor) in E. coli.
• 1978, genes for human insulin cloned
• 1979, human growth hormone cloned
• 1980, Genentech raised 35 million with IPO
  (initial 35, 88 after one hour)

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Genentech Timeline

• 1982, human insulin, licensed to Eli Lilly and
  Co., first recombinant drug to be marketed
• 1984, Produce Factor VIII, a clotting factor for
  bleeding in hemophiliacs
• 1985, Protropin, growth hormone for children with
  HGH deficiency, first recombinant pharmaceutical
  to be produced and marketed by a biotech company

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Genentech, Timeline

• 1986, interferon alpha-2a licensed to Hoffmann-La
  Roche, Inc. for treatment of hairy cell leukemia
• Instituted the Uninsured Patients Program, free
  HGH for financially need patients in the US.
• In 1988, Genetic engineering becomes a public
  debate and Genentech stocks drop so I bought
  some.
• 1989, opened largest corporate sponsored day care
  center

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Genentech, Timeline

• 1990several new products
• Actimmune interferon gamma-1b
• Activase blot clots in lungs
• Hepatitis B vaccine
• Pulmozyme for treating cystic fibrosis
• Factor VIII for treating hemophilia-A
• 1993, launches Access Excellence
• 1995, Roche Holding, Ltd agreement to purchase
  outstanding common stock

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Genetech

• Named 9 times to Working Mother magazines list
  of the 100 best companies for working mothers
• 1999- Roche exercises its option and purchases
  all of Genentechs shares
• 2000-Genentech ranks 32 in Fortune Magazines
  list of 100 best companies to work for in America

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Biopharmaceutical Categories

• Biopharamaceuticals can be grouped into six
  categories.
• Cytokines
• Enzymes
• Hormones
• Clotting Factors
• Vaccines
• Monoclonal Antibodies

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Cytokines

• Cytokines - Cytokines are hormone-like molecules
  that can control reactions between cells. They
  activate immune-system cells such as lymphocytes
  and macrophages.
• Interferon - potent glycoprotein cytokine that
  act against viruses and uncontrolled cell
  proliferation
• Interleukins function as messengers for various
  steps in the immune process. Ex. interleukin-2
  (IL-2) stimulates T lymphocytes, a recombinant
  variant of IL-2, aldesleukin (Proleukin), for
  treating renal cell carcinoma. IL-3 stimulates
  bone marrow stem cells. IL-1 secreted by
  macrophages induces fever.

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Cytokines

• Cytokines
• Granulocyte-colony stimulating factor (G-CSF)
  stimulates the bone marrow to produce neutrophils
  (antibacterial leukocytes), used for cancer
  treatments that are immunodepressants
• Granulocyte-macrophage colony-stimulating factor
  (GM-CSF) stimulates the bone marrow to produce
  neutrophils and macrophages. For chemo and radio
  therapy that suppresses bone marrow function

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Enzymes

• Enzymes are complex proteins that cause a
  specific chemical change in other substances
  without being changed themselves.
• Alteplase dissolves blood clots
• Dornase alfa a recombinant DNAse I that digests
  DNA in the mucous secretions in lungs
• Imiglucerase. A recombinant glucocereborsidase
  for Gauchers disease (bone destruction and
  enlargement of the liver and spleen)

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Other Biopharmaceutical categories

• Hormones chemicals that transfer information
  and instructions between cells in animals and
  plants. Ex. insulin, HGH.
• Clotting Factors any factor in the blood that
  is essential for the blood to coagulate.
• Vaccines microorganisms that can be used to
  stimulate resistance in a human to specific
  diseases. Ex. Hepatitis B virus, Ebola virus
• Monoclonal antibodies immortal cells created by
  fusion of a cancer cell with an antibiotic
  producing spleen cell.

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Cloning Insulin
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Human Growth Hormone

• Facts
• Peak production during adolescence
• 60 year old secretes 25 of a 20 year old
• Anterior lobe of the pituitary gland
• Primarily released in pulses during beginning
  phases of sleep
• Converted in the liver into insulin-Like Growth
  Factor type I
• Incidence 1 out of 4,000 to 10,000 births

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Human Growth Hormone

• Also known as somatotropin
• Most abundant hormone secreted by the pituitary
  gland

The Pituitary gland is a small, pea-sized gland
that is located in the middle of your skull, just
below the hypothalamus. From
http//www.optioncare.com/growthhormone/background
.htm
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Pituitary Gland

• The pituitary gland has two lobes, anterior and
  posterior
• The anterior lobe also produces
• Prolactin breast milk
• FSH, LS sexual reproduction
• Thyrotropin thyroid function
• Adrenocorticotropin - adrenal function
• Growth Hormone - growth

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Human Growth Hormone

• Usually the first hormone to be lost or reduced
• Can be congenital
• Can be acquired
• Inflammation
• Surgery
• Radiation
• Autoimmune disease
• Tumors

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Human Growth Hormone

• 191 amino acid (approx. 22 kdal)
• Appears to be 5 variants of the gene on
  chromosome 17
• Takes 80 cadavers for one years worth of therapy
• Creutzfeldt-Jacob syndrome (odds 1500)

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Study Guide

• Forever remember Genentech.
• Know and be able to describe at least 5 different
  categories of biopharmaceuticals.
• Know the definition of a biopharmaceutical.
• Be able to discuss the scientific basis and
  social value of two different biopharmaceuticals.