Introduction

• In the past most drugs have been discovered either

by identifying the active ingredient from traditional
remedies or by serendipitous discovery.
• But now we know diseases are controlled at
molecular and physiological level.
• Also shape of an molecule at atomic level is well
understood.
• Information of Human Genome
History of Drug
Discovery :
Pre 1919
•Herbal Drugs
1970s
•Rise of Biotechnology
1980s
•Commercialization of
•Serendiptious discoveries •Use of IT Drug Discovery
•Combinatorial Chemistry

1920s, 30s 1960s 1990s

•Vitamins •Breakthrough in Etiology •Robotics
•Vaccines •Automation

1940s 1950s
•Antibiotic Era •New technology,
•R&D Boost due to WW2 •Discovery of DNA
Drug Discovery and Development:
1.Early History of Pharmacy
2.Drug Discovery and Development in the
Middle Ages
3.Foundation of Current Drug Discovery and
Development
4.Beginnings of Modern Pharmaceutical
Industry
5.Evolution of Drug Products
Drug discovery and development has a long
history and dates back to the early days of
human civilization.

In those ancient times, drugs were not just

used for physical remedies but were also
associated with religious and spiritual
healing. Sages or religious leaders were
often the administrators of drugs.
 The early drugs or folk medicines
were mainly derived from plant products, and
supplemented by animal materials and minerals.
These drugs were most probably discovered
through a combination of trial and error
experimentation and observation of human and
animal reactions as a result of ingesting such
products.
Folk medicines were the only available
treatments until recent times.
Drug discovery and development started- to
follow scientific techniques in the late 1800s.
From then on, more and more drugs were
discovered, tested and synthesized in large-
scale manufacturing plants, as opposed to the
extraction of drug products from natural sources
in relatively small batch quantities.
Although pharmaceutical drugs are now widely
used worldwide, many ethnic cultures have
retained their own folk medicines.
In certain instances, these folk medicines exist
side by side and are complemented by
pharmaceutical
Drugs.
 Egyptian Medicine

Ancient papyrus provided written records

of early Egyptian medical knowledge. The
Ebers papyrus (from around 3000 BC)
provided 877 prescriptions and recipes for
internal medicine, eye and skin problems,
and gynecology.
Medications were based mainly on herbal
products.
 Indian Medicine
The Indian folk medicine, can be traced back 3000-5000 years,
and was practiced by the Brahmin sages of ancient times.
The treatments were set out in sacred writings called Vedas.
The materia medica are extensive and most are based on
herbal formulations.
Some of the herbs have
appeared in Western
medicines.
Some of the Greek medical ideas were derived
from the Egyptians, Babylonians, and even the
Chinese and Indians.
The greatest Greek contribution to the medical
field is perhaps to dispel the notion that
diseases are due to supernatural causes or spells.
The Greeks established that diseases result
from natural causes. Hippocrates, the
father of medicine, at about 400 BC is
credited with laying down the ethics for
p h y s i c i a n s.
 Greek Medicine
Some examples
Castor oil was prescribed as a laxative; linseed or flex
seed were used as a soothing
emollient, laxative and antitussive.
Other treatments include fennel plant for relief of
intestinal colic and gas, and asafetida gum resin as an
antispasmodic.
 Asclepius: Greek God of Medicine
In Greek mythology, Asclepius, the god of medicine,
studied medicine under Chiron. He excelled over
Chiron, and his medical skills were reputed to be
able to bring back the dead. This incurred the wrath of
Pluto, the god of the underworld, and the envy of
other gods. They complained to Zeus, who also
thought that he alone should have the power of life
and death. Zeus slew Asclepius with a thunderbolt.
However, Asclepius’ daughters, Panacea and Hygeia,
survived and carried on to tend to the sick.
Roman Medicine
As great administrators, the Romans instituted hospitals, although
these were used mainly to cater for the needs of the military.
Through this work, organized medical care was made available.
 Roman Medicine
The Romans also extended the pharmacy
practice of the Greeks. Dioscorides and Galen
were two noted physicians in Roman days.
Dioscorides’ Materia Medica contains
descriptions of treatments based on 80% plant,
10% animal and 10% mineral products.
Drug Discovery and Development
in the Middle Ages
The Middle Ages, from around 400 to 1500,
witnessed the decline of the Roman influences.
This was also the time when plagues scourged many
parts of Europe. Diseases such as bubonic plague,
leprosy, smallpox, tuberculosis and scabies were
rampant. Many millions of people succumbed to
these diseases.
 The Early Church
There are some references to herbs in the
Bible. However, the Church’s main contribution to
medicines is the preservation and transcription of
Greek medical manuscripts and treatises.
This enabled the knowledge developed in the ancient
times to be continued and later used in the
Renaissance period.
 Arabian Medicine
Through trades with many regions, the Arabians learned and
extended medical knowledge. Their major contribution is
perhaps the knowledge of medical preparations and
distillation methods, although the techniques were probably
derived from the practices of alchemists.
Avicenna, around 900-1000, recorded a vast
encyclopedia of medical description
and treatment.
Another noted physician was Rhazes, who
accurately described measles and smallpox.
Foundation of Current Drug Discovery and
Development

The Renaissance period laid the foundation for

scientific thoughts in medicinal preparations
and medical treatments.
There were many advances made in anatomy,
physiology, surgery and medical treatments,
including public health care, hygiene and
sanitation.
 Beginnings of Modern Pharmaceutical
Industry
Despite the advances made in the 1800s, there were only a few drugs available for
treating diseases at the beginning of the 1900s. These
were:
•Digitalis: extracted from a plant called foxglove, digitalis stimulates the cardiac
muscles, and was used to treat cardiac conditions
•Quinine: derived from the bark of the Cinchona tree, and used to treat malaria
•Ipecacuanha: extracted from the bark or root of the Cephaelis plant,
and used to treat dysentery
•Acetylsalicylic acid: extracted from bark of willow tree, and used for the
treatment of fever
•Mercury: used to treat syphilis.

More systematic research was being performed to discover new

drugs from the early 1900s.
 Evolution of Drug Products
In the early days, until the late 1800s, most drugs were based
on herbs or extraction of ingredients from botanical sources.
The synthetic drugs using chemical methods were heralded at
the beginning of the 1900s, and the pharmaceutical industry
was founded.

Many drugs were researched and manufactured, but mostly

they were used for therapeutic purposes rather than
completely curing the diseases.
Evolution of Drug Products
From the early 1930s, drug discovery concentrated on
screening natural products and isolating the active
ingredients for treating diseases. The active ingredients are
normally the synthetic versionof the natural products.

These synthetic versions, called new

chemical entities (NCEs) have to go
through many iterations and tests to
ensure they are safe, potent and effective.
 DRUG
DISCOVERY
Drug Discovery &
Development-Timeline
PRECLINICAL

CLINICAL TRIALS FDA

10,000 250 REVIEW 1 FDA
COMPOUNDS COMPOUNDS 5 COMPOUNDS APPROVED
DRUG

~6.5 YEARS ~7 YEARS ~1.5 YEARS

Drug
Discovery
• Drugs Discovery
methods:
– Random Screening
– Molecular Manipulation
– Molecular Designing
– Drug Metabolites
– Serendipity
 Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studies Trials and
Therapeutics
• Cellular and • Synthesis and • Library • Drug Affinity • Animal
Genetic Isolation Development and models of
Targets Selectivity Disease States

• Genomics • Combinatorial • SAR Studies • Cell Disease • Behavioural

Chemistry Models Studies

• Proteomics • Assay • In Silico • MOA • Functional

development Screening Imaging

• Bioinformatics • High- • Chemical • Lead • Ex-Vivo

Throughput Synthesis Candidate Studies
Screening Refinement
 Target Selection
• Target selection in drug discovery is defined as the
decision to focus on finding an agent with a particular
Cellular & biological action that is anticipated to have therapeutic
Genetic
Targets utility — is influenced by a complex balance of
scientific, medical and strategic considerations.
Genomics • Target identification: to identify molecular targets that
are involved in disease progression.
Proteomics • Target validation: to prove that manipulating the
molecular target can provide therapeutic benefit for
patients.
Bioinformatics

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Target Selection
Biochemical Classes of Drug Targets
G-protein coupled receptors - 45%
Cellular &
Genetic enzymes - 28%
Targets hormones and factors - 11%
Genomics ion channels - 5%
nuclear receptors - 2%
Proteomics
Proteomics
Techniques for Target Identification
Bioinfomatic Bioinformatics
s
Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 Cellular & Genetic Targets:
Involves the identification of the function of a potential therapeutic
drug target and its role in the disease process.
Cellular & Cellular &
Genetic Genetic Targets
Targets For small-molecule drugs, this step in the process involves identification
of the target receptors or enzymes whereas for some
Genomics biologic approaches the focus is at the gene or transcription level.

Proteomics Drugs usually act on either cellular or genetic chemicals in the

body,
known as targets, which are believed to be associated with disease.
Bioinformatics

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Cellular & Genetic Targets:
Scientists use a variety of techniques to identify and
Cellular &
isolate individual targets to learn more about their
Genetic functions and how they influence disease.
Targets

Genomics
Compounds are then identified that have
various interactions with the drug targets that
Proteomics
might be helpful in treatment of a specific disease.
Bioinformatics

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Genomics:
The study of genes and their function. Genomics aims
to understand the structure of the genome, including the
Cellular & mapping genes and sequencing the DNA.
Genetic
Targets
Seeks to exploit the findings from the sequencing of the human
Genomics and other genomes to find new drug targets.

Proteomics
Human Genome consists of a sequence of around 3 billion
nucleotides (the A C G T bases) which in turn probably encode
35,000 – 50,000 genes.
Bioinformatics

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Genomics:
Drew’s estimates that the number of genes implicated in
disease, both those due to defects in single genes and those
Cellular & arising from combinations of genes, is about 1,000
Genetic
Targets
Based on 5 or 10 linked proteins per gene, he proposes that the
Genomics number of potential drug targets may lie between 5,000
and 10,000.

Proteomics
Single Nucleotide Polymorphism (SNP) libraries: are used to
compare the genomes from both healthy and sick people and to
Bioinformatics identify where their genomes vary.

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Proteomics:
It is the study of the proteome, the complete set of proteins
produced by a species, using the technologies of large – scale
Cellular & protein separation and identification.
Genetic It is becoming increasingly evident that the complexity of
Targets biological systems lies at the level of the proteins, and that genomics
alone will not suffice to understand these systems.
Genomics
It is also at the protein level that disease processes become
manifest,
Proteomics and at which most (91%) drugs act.
Therefore, the analysis of proteins (including protein-protein,
Bioinformatics protein- nucleic acid, and protein ligand interactions) will be utmost
importance to target discovery.
Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 Proteomics:
Proteomics is the systematic high-throughput
separation and characterization of proteins within
Cellular &
Genetic
biological systems.
Targets Target identification with proteomics is performed
comparing
by the protein expression levels in normal and
Genomics
diseased tissues.

Proteomics 2D PAGE is used to separate the proteins, which

subsequently
are identified and fully characterized with
MS/MS.
LC-
Bioinformat
ics

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Bioinformatics:
Bioinformatics is a branch of molecular biology that involves extensive analysis
of biological data using computers, for the purpose of enhancing biological
Cellular & research.
Genetic Cellular &
Targets Genetic Targets
Genomics It plays a key role in various stages of the drug discovery process including
 target identification

Proteomics  computer screening of chemical compounds

and
 pharmacogenomics
Bioinformatics

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Bioinformatics:
Bioinformatics methods are used to transform the raw sequence
into meaningful information (eg. genes and their
Cellular & encoded proteins) and to compare whole genomes (disease vs.
Genetic not).
Targets Can compare the entire genome of pathogenic and
Genomics non- pathogenic strains of a microbe and identify
genes/proteins associated with pathogenism

Proteomics
Using gene expression micro arrays and gene chip technologies,
a single device can be used to evaluate and compare
the expression of up to 20000 genes of healthy and
Bioinformatics
diseased individuals at once

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Lead Discovery:
• Identification of small molecule modulators
Synthesis and
Isolation of protein function
Combinatorial
• The process of transforming these into high-
Chemistry
content lead series.
Assay
Development

High
Throughput
Screening

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Synthesis and Isolation:
• Separation of mixture
Synthesis and
Isolation • Separation of impurities
Combinatorial • In vitro chemical
Chemistry
synthesis
Assay
Development • Biosynthetic intermediate
High
Throughput
Screening

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Combinatorial Chemistry:
Rapid synthesis of or computer simulation of
Synthesis and large no. of different but structurally related
Isolation
molecules
Combinatorial
Chemistry • Search new leads
Assay
• Optimization of target affinity &
Development selectivity.
High
Throughput
• ADME
Reduceproperties
toxicity and eliminate side
Screening
effects
Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 Assay Development
• Used for measuring the activity of a
Synthesis and
Isolation
drug.
Combinatorial
• Discriminate between compounds.
Chemistry
• Evaluate:
• Expressed protein targets.
Assay
Development • Enzyme/ substrate
High interactions.
Throughput
Screening

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 High throughput screening:
• Screening of drug target against selection
Synthesis and
Isolation of chemicals.
Combinatorial
• Identification of highly target specific
Chemistry
compounds.
Assay
Development

High
Throughput
Screening

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 High throughput screening:
Synthesis and
Isolation

Combinatorial
Chemistry

Assay
Development

High
Throughput
Screening

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Medicinal Chemistry:
• It’s a discipline at the intersection of
Library synthetic
Development
organic chemistry and parmacology.
SAR Studies
• Focuses on small organic molecules (and not
on biologics and inorganic compounds)
In Silico • Used in discovery (hits)
• Drug
Screening
• Lead optimization (hit to
Chemical
Synthesis • lead)
Process chemistry and
Target
development
Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 Library Development:
• Collection of stored chemicals along
Library
Development with associated database.
• Assists in High Throughput Screening
SAR Studies
• Helps in screening of drug target (hit)
In Silico
Screening • Based on organic chemistry
Chemical
Synthesis

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 SAR Studies:
• Helps identify pharmacophore
Library
Development
• The pharmacophore is the precise section of
the molecule that is responsible for
SAR Studies biological activity
In Silico
• Enables to prepare more active compound
Screening • Allow elimination of excessive functionality
Chemical
Synthesis

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 SAR Studies:
Library
Development

SAR Studies

In Silico
Screening

Chemical Morphine Molecule

Synthesis

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 In silico screening:
• Computer simulated screening of chemicals
Library
Development • Helps in finding structures that are most
likely
SAR Studies
to bind to drug target.
In Silico
Screening
• Filter enormous Chemical space
• Economic than HTS
Chemical
Synthesis

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Chemical Synthesis:
• Involve production of lead compound in
Library
Development suitable quantity and quality to allow large
scale animal and eventual, extensive
SAR Studies
human clinical trials
In Silico • Optimization of chemical route for bulk
Screening
industrial production.
Chemical
Synthesis • Suitable drug formulation
Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 In Vitro Studies:
• (In glass) studies using component of organism i.e. test
Drug Affinity tube experiments
and Selectivity • Examples-
Cell Disease • Cells derived from multicellular organisms
Models • Subcellular components (Ribosomes, mitochondria)
• Cellular/ subcellular extracts (wheat germ,
MOA
reticulocyte
extract)
Lead Candidate
Refinement • Purified molecules (DNA,RNA)

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 In Vitro Studies:
Advantages:
Drug Affinity • Studies can be completed in short period of time.
and Selectivity
• Reduces risk in post clinical trials
Cell Disease • permits an enormous level of simplification of the
Models
system
• investigator can focus on a small number of components
MOA

Lead Candidate
Refinement

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Drug affinity and selectivity
• Drug affinity is the ability of drug to bind to its
Drug Affinity biological target (receptor, enzyme, transport system,
and Selectivity etc.)
Cell Disease • Selectivity- Drug should bind to specific receptor site on
Models the cell (eg. Aspirin)

MOA

Lead Candidate
Refinement

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Cell disease models
• Isogenic human disease models- are a family of cells that are
Drug Affinity selected or engineered to accurately model the genetics of a
and Selectivity specific patient population, in vitro

Cell Disease
Models • Stem cell disease models-Adult or embryonic stem cells carrying
or induced to carry defective genes can be investigated in vitro to
understand latent molecular mechanisms and disease
MOA
characteristics
Lead Candidate
Refinement

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Lead Candidate refinement
• Optimizing chemical hits for clinical trial is commonly
Drug Affinity referred to as lead optimization
and Selectivity • The refinement in structure is necessary in order to improve
Cell Disease • Potency
Models • Oral Availability
• Selectivity
MOA
• pharmacokinetic properties
Lead Candidate • safety (ADME properties)
Refinement

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 In vivo studies
• Its experimentation using a whole,
Animal models of
Disease States living organism.
Behavioural
• Gives information about,
Studies
• Metabolic
Functional profile
Imaging
• Toxicology
Ex-Vivo Studies • Drug interaction
Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 Animal models of disease
•states
Test conditions involving induced disease
Animal models of
or injury similar to human conditions.
Disease States
• Must be equivalent in mechanism of cause.
Behavioural • Can predict human toxicity in 71% of the
Studies
cases.
Functional • Eg. SCID mice-HIV
Imaging
NOD mice- Diabetes
Ex-Vivo Studies Danio rerio- Gene function

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Behavioural Studies
• Tools to investigate behavioural results of drugs.
Animal models of
Disease States
• Used to observe depression and mental disorders.
• However self esteem and suicidality are hard to
Behavioural
Studies
induce.
• Example:
• Despair based- Forced swimming/ Tail
Functional
Imaging suspension
• Reward based
Ex-Vivo Studies • Anxiety Based

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Functional Imaging:
• Method of detecting or measuring changes
Animal models of
Disease States
in metabolism, blood flow, regional chemical
composition, and absorption.
Behavioural
Studies
• Tracers or probes used.
• Modalities Used-
Functional
Imaging
• MRI
Ex-Vivo Studies • CT-Scan

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Ex-Vivo Studies:
• Experimentation on tissue in an artificial
Animal models of
Disease States
environment outside the organism with
the minimum alteration of natural
Behavioural
Studies
conditions.
• Counters ethical issues.
Functional
Imaging • Examples:
• Measurement of tissue
Ex-Vivo Studies
properties
• Realistic models for surgery
Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 Clinical trials:
• Set of procedures in medical research
Phase-I and drug development to study the
safety and efficacy of new drug.
Phase-II
• Essential to get marketing approval from
Phase-III
regulatory authorities.
• May require upto 7 years.
Phase-IV

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Phase 0:
• Recent designation, also known as human micro-
dosing studies.
Phase-I • First in human trials, conducted to study exploratory
investigational new drug.
Phase-II
• Designed to to speed up the development of
promising drugs.
• Concerned with-
Phase-III
• Preliminary data on the drug’s
pharmacodynamics and pharmacokinetics
Phase-IV • Efficacy of pre-clinical studies.

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Phase I:
• Clinical Pharmacologic Evaluation
Phase-I • First stage of testing in human
subjects.
Phase-II
• 20-50 Healthy Volunteers
Phase-III • Concerned With:
– Human Toxicity.
Phase-IV – Tolerated Dosage Range
Target
– Pharmacology/dynamics
Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 Phase I:
Types of Phase-I
Phase-I Trials
• SAD (Single Ascending Dose)
• MAD (Multiple Ascending
Phase-II Dose)
• Food effect
Phase-III

Phase-IV

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 Phase II:
• Controlled Clinical Evaluation.
Phase-I • 50-300 Patients
• Controlled Single Blind
Phase-II Technique
• Concerned With:
Phase-III – Safety
– Efficacy
Phase-IV – Drug Toxicity
– Drug Interaction
Target Lead Medicinal In Vitro In Vivo Clinical
Selection Discovery Chemistry Studies Studie Trials
 Phase III:
• Extended Clinical Trials.
Phase-I • Most expensive & time
consuming.
Phase-II • 250-1000 Patients.
• Controlled Double Blind
Phase-III
Technique.
• Concerned With:
Phase-IV
– Safety, Efficacy
Target
– Comparison
Lead with other Drugs
Medicinal In Vitro In Vivo Clinical
Selection– Package InsertChemistry
Discovery Studies Studie Trials
 Phase IV:
• Post Marketing Surveillance.
Phase-I • Designed to detect any rare or long-
term
Phase-II adverse effects.
• Adverse Drug Reaction Monitoring.
Phase-III
• Pharmacovigilance.

Phase-IV

Target Lead Medicinal In Vitro In Vivo Clinical

Selection Discovery Chemistry Studies Studie Trials
 DRUG
DISCOVERY
Drug Discovery &
Development-Timeline
PRECLINICAL

CLINICAL TRIALS FDA

10,000 250 REVIEW 1 FDA
COMPOUNDS COMPOUNDS 5 COMPOUNDS APPROVED
DRUG

~6.5 YEARS ~7 YEARS ~1.5 YEARS

Gene
Therapy
• Technique for correcting
defective genes.
• It is the process of inserting
genes into cells to treat
diseases.
• Gene therapy is used to
correct a deficient phenotype.
Gene Therapy-
Approaches
Germline Gene Therapy
Sperm or eggs, are modified by the introduction of functional genes, which
are integrated into their genomes.

Change would be heritable and would be passed on to later generations.

Somatic Gene Therapy

The therapeutic genes are transferred Into the somatic cells of a patient.

Change will not be inherited by the patient's offspring or later generations.

Gene Therapy-
Types
Ex Vivo Gene Therapy
Transfer of therapeutic genes in cultured cells which are then reintroduced
into patient.

Eg: Therapy for ADA Deficiency

In Vivo Gene Therapy

The direct delivery of genes into the cells of a particular tissue is referred
to as in vivo gene therapy.

Eg: Therapy for Cystic

fibrosis
Gene Therapy-
Vectors
• Viruses Retroviruses
Adenoviruses
Adeno-associated viruses Herpes
Simplex viruses
• Pure DNA Constructs
• Lipoplexes
• DNA Molecular
Conjugates
• Human Artificial
Chromosome
Gene Therapy-
Limitations
• Short lived nature of gene
therapy
• Immune response
• Problems with viral vectors
• Multigene disorders
Recent
Developments
• Nanotechnology + gene therapy yielded treatment to
torpedo cancer
• Results of world's first gene therapy for inherited
blindness show sight improvement
• New Method of Gene Therapy Alters Immune Cells
for
Treatment of Advanced Melanoma
• Preclinical
Dual Gene Therapy Suppresses Lung Cancer in
Test
Orphan Drugs:
• An orphan drug is a pharmaceutical agent that has been
developed specifically to treat a rare medical condition,
the condition itself being referred to as an orphan
disease.
• National Organization for Rare
Disorders

• European Organization for Rare

Diseases
Advantages
:•
Tax incentives.
• Enhanced patent protection and marketing
rights.
• Clinical research financial subsidization.
• Rise in research and developmen.
• Crown Corporation.
Orphan Drugs
Act:
• 4 January 1983
th

• 6000 Orphan Diseases

• Unprofitable Drug
Development
• Affecting < 2,00,000 Persons
• Orphan Drug Status to 1,090
Drugs Tourette
Syndrome
• 1985 Amendment- Marketing An Orphan Disease
Exclusivity
FDA Orphan Drug
Approvals: % Share

2 Big Pharma
19
43
Small Biopharma
17
Established
19 Biopharma
Small & Medium
Pharma
Rare Diseases & Orphan
Drugs:
Sr. Disease Cause Orphan Drug

1. Gaucher’s Disease Glucocerbrosidase Enzyme Miglustat

2. Fabry’s Disease Galactosidase Enyme Galsidase β

3. Mucopolysaccharidosis Lysosomal Enzyme Laronidase

4. Tourette’s Syndrome Motor Tics Lamotrizine

5. Crohn’s Syndrome Unknown Infliximab

6. Wilson Disease Copper Deposition Trientine

7. SCID Adenosine Deaminase Enzyme Pegadimase