Adv lec2

Advanced Pharmaceutical
Biotechnology Phar571
Lec. 2
Dr. Yara Al Tall
JUST / Faculty of Pharmacy

Pharmaceuticals and Biotechnology-
Benefits of Combination
When the two disciplines- pharmaceuticals and
biotechnology- come together, they result in
many advantages for humankind in terms of
healthcare.

This is possible through Pharmacogenomics
(derived from 'pharmacology' and 'genomics')
which refers to the study of how the genetic
inheritance affects individual human body's
response to drugs.

Biopharmaceutical drugs aim at designing and
producing drugs that are adapted to each person’s
genetic makeup.

Thus pharmaceutical biotechnology companies
may develop tailor-made medicines for maximum
therapeutic effects.

Also, biotechnology drugs can be given to the
patients in appropriate dosages as the doctor would
know the patient’s genetics and how the body
processes and metabolizes a medicine.

One more benefit of pharmaceutical biotechnology is
in the form of better vaccines. Biotech companies
design and produce safer vaccines by organisms that
are transformed through genetic engineering. These
biotech vaccines minimize the risks of infection.

Pharmaceutical Biotechnology Products

The common pharmaceutical biotechnology
products:

1. Antibodies- Antibodies are proteins that are
produced by white blood cells and are used by
the immune system to identify bacteria, viruses,
and other foreign substances and to fight them
off.
 In the recent years, monoclonal antibodies are one
of the most exciting developments in biotechnology
pharmaceuticals.

2. Proteins - Proteins made of amino acids are large,
complex molecules that do most of the work in
cells and are required for the structure, function,
and regulation of the body’s tissues and organs.

Proteins do most of the work in
the cell
Enzyme
Protease
Transport
Degrades Protein
Hemoglobin
Motion Carries O2
Actin
Contracts Muscles
Regulation
Insulin
Controls Blood Glucose
Support
Keratin
Defense Forms Hair and
Antibody Nails
Fights Viruses

 Protein biotechnology is
emerging as one of the key
technologies of the future
for understanding the
development of many
diseases like cancer or
sickle cell anemia.

3. Recombinant DNA Products - Recombinant
Deoxyribonucleic Acid is the genetically engineered
DNA created by recombining fragments of DNA
from different organisms.

 Some of the Recombinant DNA Products include:
A. Recombinant DNA Vaccines
B. Recombinant DNA Drugs
C. Recombinant DNA Enzymes
D. Recombinant DNA Growth Hormone
E. Recombinant DNA Insulin
F. Recombinant DNA Proteins
G. Recombinant DNA Yeast

Biotech's First Wave: Recombinant DNA
Drugs
In this section we will focus mainly on Drug Biotech
companies (started as biotech firms) rather than the
"Big Pharma" companies (Pfizer, J&J, Merck, Abbott,
Bayer, Roche, etc) - many of which license biotech
drugs and may even have developed a few of their
own (Lilly is an exception).

The following is a list for many of the best rDNA
drugs on the market today classified according to
their companies:

The best rDNA drugs on the market today

1. Amgen:
A. Epogen/Procrit:
This drug produces rErythropoetin.

 Epo binds the Epo receptor (Epo R) on bone
marrow erythroid progenitors, inducing
proliferation, maturation, and differentiation of
red blood cells.

Figure 1. Erythropoietin (Epo)
binds its receptor (Epo R) on the
surface of red blood cell
progenitors in the bone marrow.
It causes proliferation,
maturation, and differentiation,
thereby preventing or correcting
anemia.
Epo may also bind Epo R
expressed on the surface of
cancer cells and may elicit tumor
growth via cell proliferation,
protection from apoptosis, and/or
angiogenesis. [Note: figure
adapted from Brower, V. (2003)
Nat. Med. 9:1439.]

 why Epogen/Procrit are prescribed and what they do in
the body?

 For patients with anemia due to Dialysis/ Chronic Kidney
Disease / Renal Failure / Chemo / HIV
 Stimulates production of RBCs.
 Truly revolutionized treatment of anemia!
Epo: For patients on dialysis with anemia.
Procrit: For non-dialysis use only = Cancer, Chronic
Kidney Disease, HIV (anemia due to Zidovudine treatment
AZT); some blood transfusions.

B. Aranesp
This drug also produces rErythropoetin.

 Uses:
For patients with anemia due to Dialysis/
Chronic Kidney Disease / Renal Failure / Chemo

 It has a longer lasting effect (3X greater that
Epo), requires fewer injections - 1 shot every 3
weeks, rather than once/week.

C. Neulasta
rGranulocyte colony-stimulating factor (G-CSF)

G-CSFs are glycoprotein cytokine hormones that
stimulate proliferation and growth of granulocytes (A
type of WBC filled with microscopic granules that are
little sacs containing enzymes)

 Uses:
 For Neutropenia: low WBC count febrile neutropenia
(low WBC count with fever/ infection) due to chemo,
bone marrow transplant (BMT), Acute myeloid leukemia
(AML).

D. Infergen:
rInterferon alpha.

 Question: What are interferons?
Interferons (IFNs) are proteins made and
released by host cells in response to the
presence of pathogens—such as viruses,
bacteria, or parasites—or tumor cells. They
allow communication between cells to trigger
the protective defenses of the immune system
that eradicate pathogens or tumors.

 "Noone knows exactly how interferons
work”!

 Uses
Infergen is used for patients with Chronic,
non-responding, or relapsing hepatitis C
viral (HCV) infection.

2. Biogen
This is another biotech company which has
released the following drugs:

A. Avonex

 It is rInterferon beta-1a: it "Calms" or down-
regulates the immune system

 Made in Chinese hamster ovary (CHO) cells.

 Uses:
Treatment of relapsing forms of Multiple
Sclerosis (MS). Slows the progression of MS by
regulating the body's immune response against
myelin.

Given as an IM injection once per week.

Q.Anyone knows Multiple Sclerosis ‫بلصتلالتصلب‬
‫?بلصتلالمتعدد‬
 Multiple Sclerosis (MS) is an inflammatory
disease of the Central Nervous System (CNS)
-brain and spinal cord.

 It is a disease of the "white matter" tissue.
The white matter is made up of nerve fibers
which are responsible for transmitting
communication signals both internally within
the CNS and between the CNS and the
nerves supplying rest of the body.

For more information on Multiple Sclerosis,
please have a look at the following website:

http://www.youtube.com/watch?v=qgySDmRRzxY

B. Intron A
It is rInterferon alpha-2b

 Uses:
Over 20 indications!
i. Malignant melanoma
Sales
ii. Non-Hodgkin's lymphoma exceeding
iii. Hairy cell leukemia $440
million in !
iv. Kaposi's sarcoma three years

v. Chronic hepatitis B (HBV)
vi. Chronic hepatitis C (HCV)

3. Engerix-B/Recombivax:
They are a rHepatitis B vaccine

 Uses:
Infection with HBV prevention of 1° liver cancer.

The global HBV market exceeds $1 billion dollars
annually. It will grow as more countries adopt WHO
recommendations for the vaccination of newborns,
teenagers, healthcare workers and other at-risk
populations. "

4. Amevive:

It is a protein which blocks the growth of T-cells, and
acts as an immunosuppressant. The exact mechanism of
action is complicated, however, the T-cell activity is
weakened, which reduces the symptoms of psoriasis
and the inflammation that is involved in it.

 Uses:
 Moderate-to-severe chronic plaque psoriasis
 Suppresses overactive T lymphocytes found in
autoimmune diseases

3. Chiron ( a Novartis partnership)
A. Betaseron:
It is rInterferon beta-1b.

 Uses:
Multiple Sclerosis: Significantly delays the
progression of secondary MS, including
relapsing-remitting MS.

25

B. Proleukin
It is Interleukin-2 - IL-2

 Uses:
 Cancer: Metastatic renal cell
carcinoma, and metastatic melanoma.

 IL-2 activates lymphokine-activated
killer (LAK) cells, Natural killer cells
(NK) that normally destroy tumor cells.

26

MOA:
IL-2 activates the immune system in
several ways, but the major one is to
stimulate T cell and natural killer (NK)
cell proliferation, increasing and
activating these immune system cells to
find and destroy cancer cells.

27

C. Regranex:
It is rPlatelet-derived
growth factor (PDGF).

 Uses:
Treatment of diabetic foot ulcers.
PDGF is a cytokine (growth factor) that
stimulates skin cell and blood vessel
production

29

PDGF is involved in developing protective
tissue and skin after a wound or ulcer (a
process called granulation)

 >>>>>However, FDA has concluded that
patients who use three or more tubes of
Regranex experience a five-fold increase
in the risk of cancer death compared to
patients who do not use the drug.

30

4. Genentech
A. CathFlo Activase:
It is rTPA, tissue-plasminogen activator.

 Uses:
Thrombolytic: Approved for treatment
of acute myocardial infarction (AMI),
cardiac ischemia, acute massive
pulmonary embolism, and management of
stroke.

31

Converts plasminogen to plasmin, which
activates fibrin, breaking down blood
clot.

Clot dissolution
***FDP: FIBRIN DEGRADATION PRODUCTS
32

B. TNKase
 rTPA, tissue-plasminogen activator
 TNKase can be administered over five
seconds in a single dose, fastest
administration of any thrombolytic

 Uses:
 Thrombolytic: TNKase is bioengineered
with 3 amino acid substitutions from
natural TPA: T, N and K (Thr, Asp, Lys).
=Increased Fibrin Specificity
=Long Plasma Half-Life
=Greater Resistance to Plasminogen Activator
Inhibitor-1 33

C. Pulmozyme
It is a rDeoxyribonuclease
I (rhDNase)

 Uses:
 For management of cystic
fibrosis in children 3
months - 5 years old.
Inhalation Solution –

 Pulmozyme hydrolyzes the
DNA in sputum and
airways of CF patients.
35

 MOA:

In CF patients, lungs and airways become
clogged with mucous containing high
concentrations of extracellular DNA
released by degenerating leukocytes
(neutrophils).

* Watch this!
http://www.pulmozyme.com/how-pz-
works.jsp
36

D. Neutropin
It is a rHuman growth hormone
(Somatropin; synthetic growth hormone)

 Uses:
Treatment of GHD (growth hormone
deficiency) in children and in adults

Identical to pituitary-derived hGH. Also
indicated for growth failure associated
with chronic renal insufficiency (CRI)
prior to kidney transplantation, and short
stature associated with Turner syndrome. 37

5. The 5th company is: Eli Lilly:
Worldwide
A. Humulin: revenues
of $2.5 B
It is rInsulin annually

 Uses:
 Diabetes: Used by over 3.5 million
people in the U.S. every day

38

1: Humulin pens

2: Humalog: Humalog is the brand name of
insulin lispro  which is a rapid-acting
insulin.

3: Humalog Mix (Biphasic insulin) Rapid
acting + longer acting insulin : mixture of
insulin lispro and insulin lispro protamine.

39

Lispro (Humalog ®) Eli lilly Start < 15 min.
Rapid-acting Peak 30-60min
Aspart (Novorapid®) Novo Nordisk

Short-acting Humulin ® R Eli lilly Start 30-60
(Regular: identical to min.
human insulin= Peak 4 hr
Novolin® R Novo Nordisk
unmodified)

Intermediate-acting Humulin ® N Eli lilly Start 1.5 hrs
Peak 7 hr
(Isophane insulin:
Novolin® N Novo Nordisk
insulin+protamine+zinc

Humulin® U: withdrawn Eli lilly Start 1 hr.
from market Peakless
Glargine (Lantus®) Sanofi-Aventis
cannot be combined
Long-acting with other insulins
Detemir (Levemir®) Novo Nordisk

B. Humatrope
rHuman
growth
hormone (hGH)
(Somatropin)

 Uses:
For Somatropin Deficiency Syndrome
(SDS) in adults and GHD in children due
to hypopituitarism, a pituitary tumor or
other pituitary disorder, or Turner
Syndrome.
42

C.Xigris
It is rActivated Protein C.

 Activated Protein C acts inside the blood
vessel as an anticoagulant/antithrombotic -
reduces blood clots; controls
inflammation. Activated by thrombin.

43

 Uses:

Treatment of severe sepsis, a fast-
moving, dramatic, and often fatal
acute response to infection that
claimed 215,000 lives each year (pre-
Xigris)

44

D. Forteo
It is rParathyroid hormone.

 Uses:
Treatment of osteoporosis in women
and men - Anabolic Therapy: stimulates
new bone formation, osteoblasts, bone
mineral density (BMD) and bone
strength.

45

E. Byetta
It is rGLP-1 (glucagon-like peptide-1)

 Uses:
Type II Diabetes: regulates glucose
homeostasis and enhances glucose-
dependent insulin secretion.

46

 Byetta is an incretin mimetic similar to GLP-1,
an incretin hormone that increases insulin
release & decreases glucagon secretion from
the pancreas; increases satiety/ fullness

47

 -ve:twice a day injection, but "an
appropriate option to consider when
Type II patients cannot control their
blood sugar using oral medications."

 +ve: Steady, significant appetite
suppression and weight loss in
overweight diabetic patients

48

6. Merck

One drug from Merck : Gardasil:
 It is rQuadrivalent HPV (human
papilloma virus) types 6, 11, 16, 18

 L1 capsid protein of all 4 viruses made
individually in yeast cells and combined
into one vaccine.

49

 Uses:

First Cancer Vaccine: Approved for the
immunization of:
 children aged 9 to 15 years
 adult females aged 16 to 26 years

Used for the prevention of cervical cancer,
high-grade cervical dysplasia (abnormality
in development), and warts caused by HPVs
types 6, 11, 16 and 18
50

Virtually 100% effective in protecting
against the HPV-16 and HPV-18
strains.

-ve: The wholesale price for Gardasil
will be $120 per dose; $360 for all
three doses.

51

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