Pharmacokinetics basics

1. Pharmacokinetics Basics- Absorption,
Distribution, Metabolism and Excretion
The four processes involved when a drug is taken are absorption, distribution,
metabolism and elimination or excretion (ADME).
Pharmacokinetics is the way the body acts on the drug once it is administered. It is the
measure of the rate (kinetics) of absorption, distribution, metabolism and excretion
(ADME). All the four processes involve drug movement across the membranes. To be
able to cross the membranes it is necessary that the drugs should be able dissolve
directly into the lipid bilayer of the membrane; hence lipid soluble drugs cross directly
whereas drugs that are polar do not.
Absorption
Absorption is the movement of a drug from its site of administration into the blood.
Most drugs are absorbed by passive absorption but some drugs need carrier mediated
transport. Small molecules diffuse more rapidly than large molecules. Lipid soluble
non – ionized drugs are absorbed faster. Absorption is affected by blood flow, pain
stress etc.
Acidic drugs such as asprin will be better absorbed in the stomach whereas basic drug
ike morphine will be absorbed better in the intestine. Most of the absorption of the
drug takes place in the small intestine. Since the surface area of the stomach is much

2. smaller than that of the intestine. Most of the drugs are absorbed in the small intestine
since the amount of time that the drugs spend in the stomach is less and also the
surface area of the stomach is small. If a basic drug is taken after a meal then the
activity of the drug can be reduced whereas if an acidic drug is taken after a meal then
the action of the can be noticed much more quickly, owing to the gastric absorption.
For a drug even though lipophilic to be absorbed in the intestine some portion of it
needs to be dissolved in the intestinal juices which are aqueous. There are some
substances that are partly soluble in water and it is these that will be absorbed and
then an equivalent amount will be absorbed from the undissolved portion. Thus
complete absorption will take place. There are bile salts present in the intestine which
will aid in salvation of the drug and their resultant absorption. Drugs that are
amphipathic have no problem in getting absorbed. There are some drugs that are
completely insoluble in water such drugs float as globules in the intestine but the bile
salts will emulsify these into small enough particles such that absorption can take
place. E.g. vitamins. Some of the drugs are similar to compounds found in the body
for e.g. thyroxine and such drugs can be absorbed into the system by active transport.
When drugs are injected into the muscle, subcutaneous layer absorption still has to
take place but it is less dependent on the chemical nature of the drugs since the drugs
are absorbed into the circulatory system through the small pores in the capillary walls.
Distribution
Distribution is the movement of drugs throughout the body. Determined by the blood
flow to the tissues, it is ability of the drug to enter the vasculature system and the
ability of the drug to enter the cell if required.
Plasma Protein Binding
The blood stream has the ability to transport relatively insoluble substances. These
substances are transferred by binding to the proteins which have a very amphipathic
structure. The hydrophilic group renders the protein soluble in water and the lipophilic
compounds are attracted to the lipophilic group and are loosely bound to the protein
molecule hence protein bound. Most of the drugs travel in the plasma are partly in
solution and partly bound to the plasma protein. The bound drug is inactive and the
unbound drug is active. The ratio of bound to the unbound drug varies. Binding is
reversible. Generally acidic drugs bind to albumin and basic drugs to α1 – acid
glycoprotein. Diseased state can cause a problem on the effectiveness of the drug. As
globin levels increase with age this factor should be taken into account when treating
an elderly person with a basic drug.

3. The protein bound drug is in equilibrium with the free drug. That means that once the
free drug enters the target tissue then the protein bound drug will be released to
maintain equilibrium. If two drugs bind at the same site of the protein and are
administered together then there can be problems. e.g. Warfarin and asprin.. asprin
displaces warfarin from its bound protein as a result of which there are elevated levels
of warfarin in the unbound state and this can lead to warfarin toxicity.
Tissue Distribution
After absorption most drugs are distributed in the blood to the body tissue where they
have their effect. The degree to which the drug is likely to accumulate in the tissue is
dependent on the lipophilicity and local blood flow to the tissue. Highly perfused
organs receive most of the drugs.
The role of the liver in drug distribution
After the drug is absorbed by the GI tract, it is taken up by the part of the bloodstream
called the hepatic portal system. Most of the drugs are absorbed into this system
except for the lipids which are absorbed into the lymphatic system and then delivered
into the blood by the thoracic duct into the superior vena cava.
The hepatic portal system is designed to take digested foodstuff into the liver where it
can be processed, in some cases it is stored before being distributed and it is possible
that this may happen to the drug and the drug would be metabolized before reaching
the rest of the body. Such drugs that metabolized by the liver are said to have a high
hepatic first pass. Hence drugs with a very high hepatic first pass cannot be given
orally.
The Blood–Brain Barrier (BBB)
The capillaries in the CNS are different they have pores which are sealed by the
connective tissue and hence only small molecules can cross the blood brain barrier
and the substances that can cross over have to be very lipophilic in nature. The blood-
brain barrier (BBB) is the protective mechanism of the CNS and is not present
everywhere in the brain. This is sometimes useful as it avoids some drugs from
crossing the CNS and causing deleterious effects. E.g. neuromuscular blocking agents.
Sometimes the blood brain barrier allows the transport of drugs resulting in unwanted
effect for e.g. antihistamines cross the bbb and result in drowsiness, now there are
antihistamines that are made that are not so lipophilic in nature.

4. Metabolism or Biotransformation
It is the process of transformation of a drug within the body to make it more
hydrophilic so that it can be excreted out from the body by the kidneys. This needs to
be done since drugs and chemicals are foreign substances in our body. If the drug
continues to be in the lipohilic state and is going to be filtered by the glomerulus then
it will be reabsorbed and remain in the body for prolonged periods. Hence metabolism
deals with making the drug more hydrophilic such that it can be excreted out from the
body. In some cases the metabolites can be more active than the drug itself e.g.
anxiolytic benzodiazepines.
Some enzymes are highly specific and will breakdown only compounds that they
recognize for e.g. glucose dehydrogenase. But there are some enzymes such as pepsin
which are not specific and will breakdown most soluble proteins into smaller
polypeptides or amino acids. This enzyme and many other proteolytic enzymes attack
the peptide bond that joins the amino acids to make proteins, and in this way break the
protein down.
Two types of enzymes are involved in metabolism:
Phase I Metabolism
These enzymes modify the drug chemically by processes such as oxidation, reduction
and hydrolysis or by the removal and addition of an active group.
Phase II Metabolism
These include the conjugation of a drug or a phase I metabolite with a polar group to
render it possible for excretion. e.g. sulphates and glucuronide
The deconjugation of the drug by bacterial enzymes is called the enterohepatic cycle.
Sometimes this deconjugation can lead to increased levels of drugs in the body. But
some times due to treatment with antibiotics there may be less or no deconjugation as
a result of which there will be less drug in the body.
Principal sites of metabolism are Liver and Kidney and once the drug is rendered
hydrophilic they can be easily excreted out by the bile and urine without significant
reabsorption.

5. Enzyme Induction
There are some drugs that can lead to an increase in the production of the enzyme and
as a result speed up the metabolism of the drug and hence a higher dose of the drug is
required to achieve the therapeutic effect.
Enzyme Inhibition
Some drugs result in the inhibition of certain enzymes and as a result there is an
accumulation of the drug in the body and can lead to drug toxicity. This is also a form
of drug – drug interaction.
Excretion
Excretion is the removal of the substance from the body. Some drugs are either
excreted out unchanged or some are excreted out as metabolites in urine or bile. Drugs
may also leave the body by natural routes such as tears, sweat, breath and saliva.
Patients with kidney or liver problem can have elevated levels of drug in the system
and it may be necessary to monitor the dose of the drug appropriately since a high
dose in the blood can lead to drug toxicity.
Drug Dosage and Drug levels – Basic Definitions
Half life of a drug is the time for the drug to decrease to half of its concentration.
Minimum effective concentration: below which there will be no therapeutic effect.
Maximum safe concentration: above which there will be a toxic effect The larger the
therapeutic index the more safer the drug.
Bioavailability: It describes the amount of drug that is available to the body to
produce a therapeutic effect.
Onset of action : it is the time taken for the drug to reach the minimum effective
concentration after a drug has been administered.
Peak Action: occurs when the drug reaches its highest blood or plasma concentration
Duration of action: is the length of time the drug has a pharmacological action.
References
1. Goodman & Gilman’s The Pharmacological Basis of Therapeutics by. Joel
Griffith Hardman, Lee E. Limbird, Alfred G. Gilman. 10th Ed.
2. Rang & Dale’s Pharmacology by. Humphrey Rang, Maureen Dale, James
Ritter, Rod Flower. 6th Ed.
3. PK/DB – Database for Pharmacokinetic Properties – IFSC/USP
(URL= http://miro.ifsc.usp.br/pkdb/) accessed – April 09, 2011.

6. Animation of Antimicrobial Resistance
INTRODUCTION
Antimicrobial agents represent one of the main therapeutic tools both in human and
veterinary medicine to control and treat a variety of bacterial infectious diseases.
However, during the past five decades, the use and sometimes misuse of antimicrobials
in both human and veterinary medicine has resulted in the emergence of strains of
bacteria that no longer respond to antimicrobial therapy. Not only do antimicrobial-
resistant bacterial pathogens in animals and humans pose a risk in terms of animal
health, they also affect public health when transmitted to humans as foodborne
contaminants. Thus, addressing the issue of antimicrobial resistance is one of the most
urgent priorities in the fields of public health today.
The following animation will help illustrate several mechanisms where bacteria develop
resistance to antimicrobial agents and then transfer this resistance to susceptible
bacterial strains.
Selection Pressure
The increased prevalence and dissemination of resistance is an outcome of natural
selection and should be viewed as an expected phenomenon of the Darwinian biological
principle of “survival of the fittest.”
In any large population of bacteria, a few cells will be present which possess traits that
enable them to survive in the presence of a noxious substance, in this case the ability to
fend off the action of the antimicrobial. Susceptible organisms, those lacking the
advantageous trait, will be eliminated, leaving the remaining resistant populations
behind.
With long-term antimicrobial use in a given environment, the bacterial communities
will change dramatically, with more resistant organisms increasing in proportion. This
can result in a situation where the next time an antimicrobial is needed, it may not be
effective to treat what was once an easily treatable infection.
Mechanisms of Antimicrobial Resistance
Susceptible bacteria can acquire resistance to antimicrobials by either genetic mutation
or by accepting antimicrobial resistant genes from other bacteria.
This usually occurs through one of several biochemical mechanisms:
 Mutation
 Destruction or Inactivation
 And, Efflux

7. Mutation
Mutation is a change in the DNA that can sometimes cause a change in the gene
product, which is the target of the antimicrobial.
When a susceptible bacterium comes into contact with a therapeutic concentration of
antimicrobials, like fluroquinolones, the antimicrobial can bind to the specific enzymes,
in this case, DNA gyrase. The DNA gyrase is an essential bacterial enzyme required for
DNA replication. The end result is that fluoroquinolones block bacterial DNA replication
leading to cell death. However, when spontaneous mutations occur in specific areas of
the genes encoding these enzymes, antimicrobials no longer bind efficiently. This allows
the bacterium to continue DNA replication.
Destruction or Inactivation
Many bacteria possess genes which produce enzymes that chemically degrade or
deactivate the antimicrobial, rendering them ineffective against the bacterium.
Here the antimicrobial is either degraded or modified by enzymatic activity before it can
reach the target site and damage the bacterial cell.
Efflux
Certain bacteria can often become resistant to antimicrobials through a mechanism
known as Efflux.
An efflux pump is essentially a channel that actively exports antimicrobial and other
compounds out of the cell.
The antimicrobial enters the bacterium through a channel termed a porin, and then is
pumped back out of the bacterium by the efflux pump. By actively pumping out
antimicrobials, the efflux pumps prevent the intracellular accumulation necessary to
exert their lethal activity inside the cell.
Genetic Transfer
Genetic material can be transferred between bacteria by several means, most often by:
 Conjugation
 Transformation
 And, Transduction
Conjugation
Conjugation is mediated by a particular kind of circular DNA called a plasmid, which
replicates independently of the chromosome.

8. Many plasmids carry genes that confer resistance to antimicrobials.
When two cells are in close proximity to each other, a hollow bridge-like structure,
known as a pilus, forms between twocells.
This allows a copy of the plasmid, as it is duplicated, to be transferred from one
bacterium to another.
This enables a susceptible bacteria to acquire resistance to a particular antimicrobial
agent.
Transformation
During this process, genes are transferred from one bacterium to another as “naked”
DNA.
When cells die and break apart, DNA can be released into the surrounding environment.
Other bacteria in close proximity can scavenge this free-floating DNA, and incorporate it
into their own DNA. This DNA may contain advantageous genes, such as antimicrobial
resistant genes and benefit the recipient cell.
Transduction
In this process, bacterial DNA is transferred from one bacterium to another inside a
virus that infects bacteria. These viruses are called bacteriophages or phage.
When a phage infects a bacterium, it essentially takes over the bacteria's genetic
processes to produce more phage.
During this process, bacterial DNA may inadvertently be incorporated into the new
phage DNA. Upon bacterial death and lysis (or breaking apart), these new phage go on
to infect other bacteria.
This brings along genes from the previously infected bacterium.
How Long Do Drug Patents
Last: Everything You Need to
Know

9. Drug patents will be valid for approximately 20 years. There are variables that
can influence patent life, either to extend it or, sometimes, to shorten it.12 min
read
How Long Do Drug Patents Last?
In general, a drug patent will be valid for approximately 20 years. However,
there are variables that can influence patent life, either to extend it or,
sometimes, to shorten it.
Why Is Drug Patent Life Important?
Intellectual property laws protect drug manufacture and sales through patents.
However, a large portion of a drug's patent life can expire due to research,
development, and approval time before it ever hits the market.
Once they are marketed, however, drugs make a lot of money. They are
depended upon by thousands or millions of people. If a patent for a best-
selling drug runs out, other companies can begin engineering it. People will
stop buying the original company product, costing that company a great deal
of money.
When a company owns a patent to a drug, it is sold under a brand name.
Doctors usually prescribe it using that name, which is a patented term for the
ingredients in that drug. The company has a monopoly on it until its patent
period ends (unless it attempts to extend or to renew it). The longer that drugs
have their original patents, the longer before the companies making generic
versions can manufacture those drugs to help make them more affordable.

10. What Factors Affect Reduced Drug Patent
Life?
The first factor that makes drug patent timelines vary is that the 20-year time
period begins at the time of the drug's creation. In other words, a
pharmaceutical company might be developing and getting Federal Drug
Administration (FDA) approval for a drug without selling it for eight or more
years into its patent life. This means that when the drug shows up on the
market, the patent could be good for only a few more years.
Some have considered whether it would be sensible to allow a solid 15 years
of patent life after the drug has been cleared by the FDA. However, this is a
complicated solution. Presently, drug companies already try to extend the
patent life of their drugs as much as they can. Therefore, at this point, it may
not solve anything to add more definite years of patent life to the equation.
When Can Other Companies Copy The
Previously Patented Drug?
Once a patent has ended, other drug makers can manufacture and sell the
drug as they wish. In addition to the patent's expiration, the following
conditions must be met.
 It's no longer sold under the company's name, but it is known
generically.
 In the U.S. and most countries, the generic form has to be exactly the
same as the original, in terms of how effective it is, how safe it is, its

11. use, type of dosing, its chemical ingredients, how it moves through and
affects the body, and how it works in the body.
 The generic drug company must confirm that the patents are fully
unenforceable or invalid, and there is no risk of infringement.
 The generic company is located in a country where there is no other
patent on the drug.
Then, the generic drug can be produced. The monopoly on the product no
longer exists. Companies can produce it cheaply, and it can be sold at lower
cost.
The original company may re-work the drug in a number of ways and then
attempt to renew the patent. Usually, the re-worked medicine will then
compete in the market against the generic ones. Sometimes, however, there
are faults in either the generic brand or in the original, and it must be removed
from the market.
How Do Original Companies Extend The Life
Of A Patent?
There are some ways to extend patent life. These generally tend to slow
medical advancements, as the company's aim is to keep profits coming in
rather than to make new cures. In time, it's possible that the FDA will be
tougher on those companies that use these strategies.
The Hatch-Waxman Act
This act was passed in 1984. Its chief purpose was to help balance out the
many years a company can lose in patent life while it waits for the drug to be

12. tested and certified. Extensions can be permitted in order to make up for this
lost time, but there are a few exceptions. Firstly, the extension cannot go
beyond five years, regardless of how many years the company lost while
waiting. Secondly, the actual maximum amount of years for a company to own
a patent once it's been approved is 14. Between these two numbers, there is
not much flexibility.
Pediatric Exclusivity
By seeking to test out a drug on children, a patent can be extended for six
months. This arrangement can occur two times with the same drug.
New Versions
One trick companies use is to combine the medical components in a
somewhat new way by coming up with a newer concoction of what is
essentially the same medicine. They might make a drug more tolerable via
numerous new methods. For example, they might change a particular intake
to a slow-release, or they might change from one daily dose to two, or
transition from an oral medicine to an injection.
Transcept's Intermezzo is an example of alternative delivery. The pill form of
the drug, Ambien, had been in use for several years. Intermezzo, which
dissolves under the tongue, has a lower dosage of its active chemical as well
as faster activation and a slightly different effect on the user. Therefore, it
qualified for a five-year exclusivity period, which offset the expiration of the
patent on Ambien.
New Things It Can Do

13. The FDA has a rule called the "three year new use" stipulation. It means that
when it's discovered that the drug can achieve another remedy, you can
increase the patent for three years on the basis of its new purpose.
Chemical Adjustments
Companies can make adjustments to the amount of isomers in a medicine.
When companies do so, the drug is essentially different, even though it's
achieving the same purpose. If one isomer doesn't add anything to the
purpose, it can be deleted, and then it's a new drug, ready for an extended
patent. Another term for this is "purification," meaning that when an
unnecessary chemical is taken out of the combination, it leaves behind what
really matters. Regardless, it's considered a new drug.
An example of purification is Lundbeck's Lexapro. It took only three-and-a-half
years to develop because its predecessor, Celexa, used two forms of the
molecule citalopram. Lexapro was considered a purified form because it
utilized only the one of these forms that caused the anti-depressant effect.
Because Lexapro didn't use the second form of the molecule, it was seen as a
new drug, and the FDA granted the company a five-year exclusive period.
This period corresponded to the expiration of Celexa's patent. Sometimes, as
in this case, purifications offer fewer side effects.
New Combinations
Sometimes, it isn't dangerous to combine two drugs into one. In some cases,
it may even to be found to be more effective. At least, it can have a neutral
effect. Therefore, companies have been known to fuse two medications
together, thereby coming up with a new drug for patenting. Likewise, two

14. mechanisms can be considered for one medicine, and this may also extend
patent life.
For example, Pfizer patented Caduet, a heart disease drug that included two
of its other patented drugs, Norvasc and Lipitor. The patents for the underlying
molecules of the earlier drugs expired, but because Pfizer had a patent on the
combination, no other company could produce it.
Combination drugs sometimes increase consumers' co-pays or require full
retail payment because they are new. In these cases, patients can request the
separate drugs from their doctors.
Drugs for Rare Diseases
A rare disease is defined as one that fewer than 200,000 people in the U.S.
have in any given year. In order to encourage drug companies to develop
treatments for such diseases and to keep these medicines available, a seven-
year patent extension is possible for these drugs.
30-Month FDA Stays
If a generic company applies for approval of a spoken-for patent in order to
claim a right to it, then the FDA gets involved, and a conflict and potential
court case can ensue. When this happens, the original company could receive
as much as another 30 months of patent life, unless the case is settled
sooner.
Patent Extension and Drug Costs
Since drug patents are relatively short compared to other inventions, some
may think that this lessened time accounts for their inflated costs.

15. Drugs are so expensive that many U.S. citizens simply cannot afford them.
There are stories of drugs that are so expensive that even the doctors and
researchers who study them cannot afford their purchase.
It may be believed that high costs are a result of a great deal of research and
time the companies expend bringing new drugs to market. However,
pharmaceutical analyst Richard Evans claims that the increased cost of
drugs accounted for almost 50 percent of pharmaceutical sales growth ever
since 1980, and 145 percent of U.S. sales growth over the last five years.
In other words, Evans says, the price increase is related to the price only —
not to a specific medicine or research method. The fact that companies get
away with this increase further shows the power of having ownership of the
drug patents.
Given the amount of money pharmaceutical companies bring in, it's not
necessarily the case that extending drug patents will lower the cost of drugs.
It's possible that drug prices would simply stay the same. There are many
reasons a company might argue that it must keep its prices the same in spite
of such extensions.
One recent situation involved Bristol-Myers Squibb. Through court cases, the
company managed to put off generic versions of Taxol and BuSpar. Taxol in
particular did not come out in generic form for an extremely long time. While
generic companies didn't benefit from this, Bristol-Myers did, quite
significantly.
However, Bristol-Myers spent $2 billion on ImClone, a drug that took a long
time to get on the market. Meanwhile, its competitors got ahead of the game

16. with hypertension drugs. Therefore, even though the company made headway
with the court cases, it lost half of its potential 2002 income.
This isn't a far-fetched situation; it could happen with other drug patents too.
For example, AstraZeneca is in conflict with generic drug makers over
Prilosec, a medication for acid reflux. Even if it wins that case, the money
spent there could have gone to research.
Further, drug patent loss creates major loss of income for companies. When
Pfizer lost its patent on Lipitor (used to reduce cholesterol), the company lost
19 percent of profits in the first few months after. Lilly lost 9 percent of income
in the time after Prozac went generic. Lilly also hit hard times when Zyprexa
went generic, losing 73 percent of its sales. And Merck, when losing its patent
for Pepcid, its earnings went from $755 million to $110 million.
Another interesting case is that of Amgen's 2002 acquisition of Enbrel, which
generates an annual income of $4.2 billion. The patent expired in 2013.
Amgen received the patent when it bought the company Immunex and then
shared profits with Wyeth. In 2011, Amgen received a patent on Etanercept,
an alternative to Enbrel, which extended its monopoly on the drug until 2028.
Many major drug makers argued against the patent and attempted to make
other generic forms (despite the costs of clinical trials for such apparently new
drugs).
These cases illustrate why some think that the implementation of a solid 15-
year rule is a good idea. For instance, if Prilosec had been given a 15-year
patent, there wouldn't be a long and expensive trial and delay for the generic
companies (and the public) to access it. Such a rule might change the focus of

17. drug development from its current uncertain financial status toward the
science of helping the greatest number of people.
In Australia, drug patent life was increased from 14 to 20 years. Unfortunately,
this had a major negative effect on their economy. At the time, it was done to
try to boost pharmaceutical developments. Instead, the generic drug
companies suffered to the extent of about $2 billion over eight years, and the
cost to the government was $200 million per year because lower-cost generic
drugs took longer to become available in its health-care system.
Patent Holding vs. Market Exclusivity
Whether or not a company holds a patent to a drug, there is still a question of
its market exclusivity. This is when a company owns the exclusive right to
market a drug. It was designed to balance new drug innovation with
competition from generic drugs, and it can prevent generic companies from
having a hand in drug sales. The market exclusivity and patent may be
concurrent but are not necessarily. The period of exclusivity depends on the
type of drug.
What Is a Compulsory License?
In some international markets, there is a "compulsory license," which permits
generic brands to produce patented drugs before they are legally allowed to
do so, therefore bypassing the patent. This is typically permitted in the case of
a drug or illness crisis when drugs are not affordable for the public on a mass
scale, such as in a developing country.

18. Drug Patents in Developing Countries
Drug companies who already own patents in developed countries often seek
to gain patents abroad. However, this has caused conflict between the
wealthy drug companies and the local companies and governments, who
would prefer that their own companies own the patent. There have been great
debates over the pricing and ownership of such patents in the developing
world.
India is one country where Big Pharma is trying to claim patents. With such a
large population, there is an expectation that drug sales will grow
tremendously. And since drugs are expensive, most of the providers there are
generic brands.
There are two issues for drug companies in India. First, will patent law in India
be the same as in the more developed world? Secondly, will high prices be
permitted and maintained? It is presently unclear, but the answer so far has
seemed to be "no" to both questions. India's Supreme Court supported the
country's right to deny patents, so generic drug makers have been selling
drugs which have patents elsewhere. So far, the people of India refuse to pay
the prices Big Pharma wants them to.
Novartis created Glivec, an important drug for chronic myeloid leukemia. India
rejected the patent after years of Novartis fighting for it there. It was a closely-
watched case that symbolized Big Pharma's attempted outreach to patents in
the developing world, where there is significant demand for medicine. Many
developing countries, however, want to help their own drug makers, and
therefore often don't approve patent applications from foreign makers.

19. India is a particularly important place for this battle, one that's further
complicated by poverty there. It is likely that drug sales will increase a great
deal in the country, but nearly 75 percent of sales are from generic brands.
The Reality of Patent Life
The reality is that drug patent life is not particularly long, unless one continues
to make adjustments and apply for new patents. Drug patents — just like
other kinds of patents — are bound by the 20-year limit. And, as with other
patents, that amount of time can be reduced due to other occurrences. For
example, a total of three maintenance fee payments must be made every few
years to keep the patent in force. Each payment is larger than the last, and if
they are not made, the patent expires.
Patent Maintenance Fees
Maintenance fees must be paid to keep utility patents in force. There are no
maintenance fees for plant or design patentsor for a reissue patent if it didn't
need maintenance fees before. The three maintenance fees needed are as
follows:
 Three-and-a-half years post issuance (or up to six months after that with
an added surcharge)
 Seven-and-a-half years post issuance (or 8 years after with surcharge)
 Eleven-and-a-half years post issuance (or 12 years after with
surcharge)

20. You can't pay maintenance fees more than six months early, and if you are
more than six months late, the patent can go into the public domain. In case of
an unavoidable delay, you may be able to revive the patent.
Payment amounts are as follows:
 First payment is $980
 Second payment is $2,480
 Third payment is $4,110
There may be a 50 percent decrease for small entities (making the fees $490,
$1240, and $2055). They also get reductions on late fee surcharges.
Many patents become public domain because the the patent holders don't
consider the maintenance fees worth paying. The USPTO publishes such
patents in the Official Gazette. There could be an average of 20 pages of such
patents in a given week.
Exceptions to Patent Life
Generally, patent terms are 20 years. There are a few exceptions:
 Utility and plant patents from before June 8, 1995 or filed before that
date: Their patent life is either 20 years or 17 years from the patent
grant.
 A patent from international application filed before June 8, 1995
that went national: The term is either 17 years from the grant or 20
years from filing or earlier filing date that was used — whichever is
longer.

21.  If there's a delay from the patent office: This delay will be added as a
patent term extension or a patent term adjustments.
 Design patents: These last 14 years from patent grant.
 Continuing, divisional, or continuation in part applications on or
before June 8, 1995: These will close twenty years from filing the
earliest application (from either a U.S. or international application).
 International Patent Application: If filed on or after June 8, 1995, it will
end 20 years from the filing date of international application.
 Foreign Priority: The patent will end on the date of U.S. patent filing.
 Provisional Applications: The 20-year term runs from the filing date of
a non-provisional application, only when it's accepted over the earlier
provisional one.
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Patents?
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need on UpCounsel's marketplace. UpCounsel accepts only the top 5 percent
of lawyers to its site. Lawyers on UpCounsel come from law schools such as
Harvard Law and Yale Law and average 14 years of experience, including
work with or on behalf of companies like Google, Menlo Ventures, and Airbnb.
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