Patent & other IPR concerns in Pharma, Chemical, Biotech etc

““Pharmaceutical Pharmaceutical Biotechnology & the IPR Biotechnology & the IPR concerns”concerns”

Pankaj KumarPankaj Kumar

Intellectual Property AttorneyIntellectual Property [email protected]

MonoclonalAntibodies

Genetic EngineeringTHIRD GENERATION BIOTECHNOLOGY

PharmaApplications

Chemical Applications

Patent Biotech Animal Biotech

Diagnostic Kits

IncremenatalKnowledge of

Microbio.

Microbiological of the Late early 20th CenturySECOND GENERATION BIOTECHNOLOGY

Stone Age EmpiricismSECOND GENERATION BIOTECHNOLOGY

MolecularBio. & DNA

Vaccines Antibiotics EnzymesSingle Cell

Protein

Cross Breeding

Use of Enzymes

AlcoholFermentation

PHARMACEUTICAL & BIOTECHNOLOGICAL RESEARCH AREAS

PATENTING TREND IN INDIA

Sectors USPTO(% share)

IPO(% share)

Chemical 278 (43%) 1073 (22%)

Pharmaceuticals 219(34%) 1579 (32%)

Machinery 28 (4%) 691 (14%)

Instruments 17 (3%) 200 (4%)

Biotechnology 53 (8%) 130 (3%)

Transport 6 (1%) 122 (2%)

Electrical equipment 1 (0.15%) 99 (2%)

Electronics 9 (1%) 74 (2%)

Patents granted to Indian organizations by the USPTO and IPO during 1990-2008

It has been observed from the Table that chemicals, pharmaceuticals and biotechnology were the major areas in which Indian organizations had obtained patents.

DEFINITION OF INVENTION: DEFINITION OF INVENTION: THE PATENTS (AMENDMENT) ACT, 2005-.THE PATENTS (AMENDMENT) ACT, 2005-.

Section 2(1) (j)Section 2(1) (j)

““invention” means a new product or process involving an inventive invention” means a new product or process involving an inventive step and capable of industrial application;step and capable of industrial application;

Therefore, the criteria for an invention to be patentable are,Therefore, the criteria for an invention to be patentable are,(1) An invention must be novel(1) An invention must be novel(2) has an inventive step and(2) has an inventive step and(3) is capable of industrial application (3) is capable of industrial application

Section 2(1) (ja):Section 2(1) (ja):““inventive step” means technical advancement which makes the inventive step” means technical advancement which makes the

invention not obvious to a person skilled in the art.invention not obvious to a person skilled in the art.

Non-Patentable Subject-MatterNon-Patentable Subject-Matter

All fields of technology are patentableAll fields of technology are patentable

Section 3 and 4: What are not inventionsSection 3 and 4: What are not inventions

Section 3(b): Contrary to public order and morality Section 3(b): Contrary to public order and morality Section 3(c) – discovery of living thingsSection 3(c) – discovery of living thingsSection 3(d) – new forms of a known substance Section 3(d) – new forms of a known substance Section 3(e) – composition-mere admixture Section 3(e) – composition-mere admixture Section 3(i) – method of treatment of animals and humansSection 3(i) – method of treatment of animals and humansSection 3(j) – plants, animals and parts thereof & Essentially Bio-ProcessesSection 3(j) – plants, animals and parts thereof & Essentially Bio-ProcessesSection 3(k) – computer programs per seSection 3(k) – computer programs per se

Section 3: What are not inventionsSection 3: What are not inventions

Section 3(c):

“the mere discovery of a scientific principle or the formulation of an abstract theory or discovery of any living thing or non-living substances occurring in nature”

e.g. Functional Antibodies

Section 3 (h):

“a method of agriculture or horticulture”

e.g. Method of production or Propagation of plants

Section 3 (i):

“any process for the medicinal, surgical, curative, prophylactic (diagnostic, therapeutic) or other treatment of human beings or any process for a similar treatment of animals to render them free of disease or to increase their economic value or that of their products”

e.g. Method of treatment

Section 3: What are not inventionsSection 3: What are not inventions

METHOD OF TREATMENT/DIAGNOSISMETHOD OF TREATMENT/DIAGNOSIS

Diagnostic Method/Process is not patentable, the Indian Patent Office’s Diagnostic Method/Process is not patentable, the Indian Patent Office’s purview is that since no diagnostic method on its own can render human purview is that since no diagnostic method on its own can render human being or animal free of disease.being or animal free of disease.

The “method of treatment” or “method of diagnosis” claims in India are The “method of treatment” or “method of diagnosis” claims in India are strictly not permissible.strictly not permissible.

The possible variant of such claims that are permissible by the Indian The possible variant of such claims that are permissible by the Indian Examiners are the “kit” claims.Examiners are the “kit” claims.

Section 3 (j):

“plants and animals in whole or any part thereof other than microorganisms but including seeds, varieties and species and essentially biological processes for production of propagation of plants and animals”

e.g. Cell, Tissue, Organ

Section 3: What are not inventionsSection 3: What are not inventions

ESSENTIALLY BIOLOGICAL PROCESSESSENTIALLY BIOLOGICAL PROCESS

Essentially biological process is defined as the one that “consists Essentially biological process is defined as the one that “consists entirely of natural phenomena such as crossing or selection”.entirely of natural phenomena such as crossing or selection”.

The decisive factor for categorizing a process as essentially The decisive factor for categorizing a process as essentially biological process or non-essentially biological process depends on biological process or non-essentially biological process depends on the amount of human intervention involved and its impact on the final the amount of human intervention involved and its impact on the final result.result.

BIOLOGICAL MATERIALBIOLOGICAL MATERIAL

The isolated (discovered) biological material does not The isolated (discovered) biological material does not constitute a patentable subject matter by IPO despite the fact constitute a patentable subject matter by IPO despite the fact it is characterized by specific utility.it is characterized by specific utility.

The biological material genetically modified preferably through The biological material genetically modified preferably through substantial human interventions are patentable. substantial human interventions are patentable.

Section 3(k):Section 3(k):

““a mathematical or business method or a computer programme per a mathematical or business method or a computer programme per se or algorithms”se or algorithms”

e.g. Bioinformatics Toolse.g. Bioinformatics Tools

Section 3: What are not inventionsSection 3: What are not inventions

Section 3(p):

“an invention which in effect, is traditional knowledge or which is an aggregation or duplication of known properties or traditionally known component or components”

e.g. Turmeric or Neem for therapeutics

Section 3: What are not inventionsSection 3: What are not inventions

Indian pharmaceutical industry :Indian pharmaceutical industry :Some Some FactsFacts

Growth rate ~13%Growth rate ~13%

Contributes ~22% to world’s generic drugs marketContributes ~22% to world’s generic drugs market

~80% Ingredients used by US manufacturers- produced in ~80% Ingredients used by US manufacturers- produced in India and ChinaIndia and China

More than 100 US FDA approved plants- highest outside USA. More than 100 US FDA approved plants- highest outside USA. (More than combined total of China and Italy)(More than combined total of China and Italy)

Major Therapeutic Areas of R&D in IndiaMajor Therapeutic Areas of R&D in India

• ANTIDIABETICS- highest growth rate of 26.1%ANTIDIABETICS- highest growth rate of 26.1%

• CARDIOVASCULAR-growth rate 21.3%CARDIOVASCULAR-growth rate 21.3%

• GYNAECOLOGY- growth rate 18.3%GYNAECOLOGY- growth rate 18.3%

• ANTIVIRALANTIVIRAL

• ANTI CANCERANTI CANCER

• HIV/AIDSHIV/AIDS

• GASTROINTESTINALGASTROINTESTINAL

(SO: ORGIMS data)(SO: ORGIMS data)

IPR IP

Patent Invention – synthesized formula

Trademark Aspirin (become generic now) of Bayer

Industrial designs Aesthetic designs of the container

Copyright Advertisement and other promotional material

GI Not applicable

Trade secret Best mode of the manufacturing, Trade channels, database of resources, parties details for the trading,

Generic drugsGeneric drugs

• Identical or within an acceptable bioequivalent range to the brand-Identical or within an acceptable bioequivalent range to the brand-name counterpart with respect to pharmacokinetic and name counterpart with respect to pharmacokinetic and pharmacodynamic properties pharmacodynamic properties

• Prescriptions may be issued for drugs specifying only the chemical Prescriptions may be issued for drugs specifying only the chemical name, rather than a manufacturer's name; such a prescription can be name, rather than a manufacturer's name; such a prescription can be filled with a drug of any brand meeting the specification. For example, filled with a drug of any brand meeting the specification. For example, a prescription for lansoprazole can be filled with generic lansoprazole, a prescription for lansoprazole can be filled with generic lansoprazole, Prevacid, Helicid, Zoton, Inhibitol, or MonolitumPrevacid, Helicid, Zoton, Inhibitol, or Monolitum

• In case of a generic drug of biological type (e.g. monoclonal In case of a generic drug of biological type (e.g. monoclonal antibodies), it is known as “Bio-similar”antibodies), it is known as “Bio-similar”

• generic medicines sold for significantly lower pricesgeneric medicines sold for significantly lower prices

• Reason for the relatively low price of generics is that competition Reason for the relatively low price of generics is that competition increases among producers when drugs no longer are protected by increases among producers when drugs no longer are protected by patents, incur lesser cost in creating generic (only the cost to patents, incur lesser cost in creating generic (only the cost to manufacture, rather than the entire cost of development and testing)manufacture, rather than the entire cost of development and testing)

Pharmaceutical R&DPharmaceutical R&D

• Output: INVENTIONS & INNOVATIONS - product and processesOutput: INVENTIONS & INNOVATIONS - product and processes

• Examples: new drug molecule, new chemical entity, drug design, the Examples: new drug molecule, new chemical entity, drug design, the processes etcprocesses etc

• Huge investment and effortsHuge investment and efforts

• Clinical trials (phase I, phase II and phase III)Clinical trials (phase I, phase II and phase III)

• average cost discovering and testing a new innovative drug (with a new average cost discovering and testing a new innovative drug (with a new chemical entity) has been estimated to be as much as $800 million. chemical entity) has been estimated to be as much as $800 million. Merril Goozner estimates the true cost is closer to $100–$200 million.Merril Goozner estimates the true cost is closer to $100–$200 million.

• Generic manufacturers do not incur the cost of drug discoveryGeneric manufacturers do not incur the cost of drug discovery

• Sometimes, reverse-engineering is used to develop bioequivalent Sometimes, reverse-engineering is used to develop bioequivalent versions to existing drugsversions to existing drugs

• Generic manufacturers also do not bear the burden of proving the safety Generic manufacturers also do not bear the burden of proving the safety and efficacy of the drugs through clinical trials, since these trials have and efficacy of the drugs through clinical trials, since these trials have already been conducted by the brand name companyalready been conducted by the brand name company

OptionsOptions::

Pharmaceutical industry : IPRs Pharmaceutical industry : IPRs controversycontroversy

• Certain exemptions: Bolar provisions Certain exemptions: Bolar provisions

• Ever-greening: Gleevec case Ever-greening: Gleevec case

• Some inventions should not be patented: platform Some inventions should not be patented: platform technology – HGP, biological essential processestechnology – HGP, biological essential processes

• Balancing of rights: compulsory licenses - Access to essential Balancing of rights: compulsory licenses - Access to essential medicinesmedicines

• Higher drug costs - the Doha Declaration, was issued in Higher drug costs - the Doha Declaration, was issued in November 2001, which indicated that TRIPs should not November 2001, which indicated that TRIPs should not prevent states from dealing with public health crisesprevent states from dealing with public health crises

• Export of the drugs allow to other countries where there is a Export of the drugs allow to other countries where there is a national health problem; drugs exported under such a national health problem; drugs exported under such a regime may be packaged or colored differently to prevent regime may be packaged or colored differently to prevent them from prejudicing markets in the developed world.them from prejudicing markets in the developed world.

Trade mark -Trade mark - Passing-off of Passing-off of Pharmaceutical ProductsPharmaceutical Products cough syrup cough syrup bottlesbottles

MUCOSOLVAN’ v MUCOSOLVIN’ MUCOSOLVAN’ v MUCOSOLVIN’

BIOTECHNOLOGY

Globally India is in the list of top 12 biotech markets and it is Globally India is in the list of top 12 biotech markets and it is 3rd3rd in Asia Pacific region. (Over 280 biotech companies) in Asia Pacific region. (Over 280 biotech companies)

2% share of the global biotechnology industry. 2% share of the global biotechnology industry.

By 2015, the total size of biotechnology industry in India will By 2015, the total size of biotechnology industry in India will touch US$ 25 billion. touch US$ 25 billion.

Rise in domestic business, new innovations and increase in Rise in domestic business, new innovations and increase in exports has caused the 18% growth in the year 2008-09. exports has caused the 18% growth in the year 2008-09.

Biotech Industry Facts in IndiaBiotech Industry Facts in India

1. Genetic engineering process such as:• A process for recombinant production of a growth hormone• A modified interfering Ribonucleic acid molecule• A recombinant modified virus with proper genetic intervention• A recombinant plastid vector

2. Polypeptides such as • Markers• Antibodies• Vaccines

PATENTABLE BIOTECHNOLOGICAL DOMAINS

3. Method of isolation of microorganisms from culture medium;4. Method of mutation;5. Host cells (if transformed with a cloning/expression vector)6. Mutants;7. Plasmids

PATENTABLE BIOTECHNOLOGICAL DOMAINS

NUCLEIC ACID/AMINO ACID SEQUENCES

• Must be NovelMust be Novel• Involve Human intervention Involve Human intervention • Must have a UtilityMust have a Utility

PATENTABLE NUCLEIC ACID FORMS

• cDNAscDNAs• PromotersPromoters• EnhancersEnhancers• Individual exonsIndividual exons• Expressed Sequence Tags (ESTs); only as probesExpressed Sequence Tags (ESTs); only as probes• Diagnostic kitsDiagnostic kits

The microorganisms are patentable, if:• isolated, • mutated, • adapted and • recombined successfully

MICRO-ORGANISMS

WHAT INDIAN PATENT OFFICE SAYS ABOUT WHAT INDIAN PATENT OFFICE SAYS ABOUT

BIOTECHNOLOGICAL PATENTABILITY?BIOTECHNOLOGICAL PATENTABILITY? BIOTECHNOLOGICAL INVENTIONSBIOTECHNOLOGICAL INVENTIONS NON PATENTABLE NON PATENTABLE PATENTABLE PATENTABLE

Living entities of natural originLiving entities of natural origin √√ ××

SeedsSeeds √√ ××

Plants in whole or there part thereofPlants in whole or there part thereof √√ ××

Plant VarietiesPlant Varieties √√ ××

A method of treatment or diagnosisA method of treatment or diagnosis √√ ××

A substance freely occurring in nature, if A substance freely occurring in nature, if merely found or discoveredmerely found or discovered

√√ ××

Any process of manufacture or production Any process of manufacture or production relating to living entitiesrelating to living entities

√√ ××

Contd.

BIOTECHNOLOGICAL INVENTIONSBIOTECHNOLOGICAL INVENTIONS NON PATENTABLE NON PATENTABLE PATENTABLE PATENTABLE

Micro-organismsMicro-organisms ×× √√

Cell line (if artificially produced)Cell line (if artificially produced) ×× √√

Recombinant DNA, RNA, amino acidRecombinant DNA, RNA, amino acid ×× √√

Hybridoma Technology except protoplast Hybridoma Technology except protoplast fusionfusion

×× √√

Expressed Sequence Tags (ESTs), if it Expressed Sequence Tags (ESTs), if it works as a probeworks as a probe

×× √√

Ever-greening Ever-greening

•used by a patentee of a particular drug to restrict or prevent competition from new entrant/manufacturer of generic equivalents to that drug

•Year 2002: an extensive and lengthy inquiry by the US Federal Trade Commission (FTC), found that as many as 75% of new drug applications by generic drug manufacturers experiencing legal actions under patent laws by the patentee.

•These were driving up US drug costs by keeping away the cheaper generic versions off the market

S.3(d)S.3(d) “The mere discovery of a new form of a known substance which “The mere discovery of a new form of a known substance which

does not result in the enhancement of the known efficacy of that substance or …does not result in the enhancement of the known efficacy of that substance or …

the mere discovery of any new property or new use for a known substance or ….the mere discovery of any new property or new use for a known substance or ….

the mere use of a known process, machine or apparatus unless such known the mere use of a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant.”process results in a new product or employs at least one new reactant.”

Explanation to Sec 3 (d) of Patent Act’70Explanation to Sec 3 (d) of Patent Act’70

salts, esters, ethers, polymorphs, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, metabolites, pure form, particle size, isomers, mixtures of isomers, isomers, mixtures of isomers, complexes, combinations and other complexes, combinations and other derivatives of the known substancesderivatives of the known substances

……………………..considered the same ..considered the same unlessunless

………………………………differdiffer significantly in significantly in properties with regard to properties with regard to efficacyefficacy

Novartis v. UoINovartis v. UoI

– Novartis attempted to patent beta crystalline form of imatinib mesylate, Novartis attempted to patent beta crystalline form of imatinib mesylate, already known in prior artalready known in prior art

– Controller rejects as not new, obvious and not patentable under Controller rejects as not new, obvious and not patentable under section 3(d)section 3(d)

– Declared Constitutional by the Madras High CourtDeclared Constitutional by the Madras High Court– Efficacy is the therapeutic effect in healing a disease of having a good Efficacy is the therapeutic effect in healing a disease of having a good

effect on the body. Mere increase in bio-availability does not indicate effect on the body. Mere increase in bio-availability does not indicate that there has been an enhancement in the efficacy. Hence, barred by that there has been an enhancement in the efficacy. Hence, barred by Section 3(d).Section 3(d).

Section 3(d): CasesSection 3(d): Cases

Novartis v. Cipla (December 2009)Novartis v. Cipla (December 2009)– Section 3(d) is not applicable to NCEs.Section 3(d) is not applicable to NCEs.

Ind Swift v. Cadila (Review Petition – August 2010)Ind Swift v. Cadila (Review Petition – August 2010)– Original decision of Deputy controller in January 2009Original decision of Deputy controller in January 2009– Patent application on crystalline Clopidogrel besylate; known substance was Patent application on crystalline Clopidogrel besylate; known substance was

Clopidogrel bisulphate salt and solvated forms of Clopidogrel besylateClopidogrel bisulphate salt and solvated forms of Clopidogrel besylate– Deputy Controller overruled Section 3(d) on the basis that the invention is more Deputy Controller overruled Section 3(d) on the basis that the invention is more

stable, has increased shelf life, is more free flowing and less cardiotoxic. stable, has increased shelf life, is more free flowing and less cardiotoxic. – This was upheld on Review.This was upheld on Review.

Roche v. Cipla (August 2010)Roche v. Cipla (August 2010)– Section 3(d) does not apply to processSection 3(d) does not apply to process– A pharmaceutical composition of two known substances – Section 3(d) not A pharmaceutical composition of two known substances – Section 3(d) not

attracted.attracted.

Section 3(d): CasesSection 3(d): Cases

Compulsory licensesCompulsory licenses

•Natco Pharma Ltd v Bayer

•Bayer patented drug nexavar is to treat advanced stage of kidney and liver cancer

•The drug is not a life saving but life extending and has to be taken by the patient lifetime

•The cost of therapy is INR 2,80,428/- per month

•Mar’12, India granted first compulsory license to NATCO

Bolar provision/ Research exemptionBolar provision/ Research exemption• Roche Products v. Bolar Pharmaceutical, 733 F.2d 858 (Fed. Cir. 1984)Roche Products v. Bolar Pharmaceutical, 733 F.2d 858 (Fed. Cir. 1984)

• Before patent expiration, Bolar used the patented chemical (Valium) in Before patent expiration, Bolar used the patented chemical (Valium) in experiments to determine if its generic product ‘bioequivalent’experiments to determine if its generic product ‘bioequivalent’

• The Court of Appeals rejected Bolar’s contention holding that the The Court of Appeals rejected Bolar’s contention holding that the experimental use exception did not apply because Bolar intended to sell its experimental use exception did not apply because Bolar intended to sell its generic product in competition with Roche’s Valium after patent expiration generic product in competition with Roche’s Valium after patent expiration and, therefore, Bolar’s experiments had a business purposeand, therefore, Bolar’s experiments had a business purpose

• argued - public policy in favor of availability of generic drugs immediately argued - public policy in favor of availability of generic drugs immediately following patent expiration justified the experimental use of the patented following patent expiration justified the experimental use of the patented chemical because denying such use would extend patentee monopoly chemical because denying such use would extend patentee monopoly beyond the date of patent expirationbeyond the date of patent expiration

• Argument rejected, stating such policy decisions should be made by Argument rejected, stating such policy decisions should be made by CongressCongress

• Law permitting use of patented products in experiments for the purpose of Law permitting use of patented products in experiments for the purpose of obtaining FDA approval pass (section 271-e-1 of the Drug Price Competition obtaining FDA approval pass (section 271-e-1 of the Drug Price Competition and Patent Term Restoration Act, informally known as the "Hatch-Waxman and Patent Term Restoration Act, informally known as the "Hatch-Waxman Act“)Act“)

Very particular while examining pharmaceutical/chemical related Very particular while examining pharmaceutical/chemical related applications;applications;

Very well-qualified and have decades of experiences in the subject Very well-qualified and have decades of experiences in the subject matters;matters;

Number of examiners is more in pharmaceutical and chemical field than Number of examiners is more in pharmaceutical and chemical field than any other fields;any other fields;

Objections of the examiners in pharmaceutical/chemical very stringent Objections of the examiners in pharmaceutical/chemical very stringent (internal circular from the Controller General as to not give very broad (internal circular from the Controller General as to not give very broad claims);claims);

Requirements to be complied with in pharmaceutical/chemical related Requirements to be complied with in pharmaceutical/chemical related applications:applications:

For pharmaceuticals in order to evade Section 3(d), applicant should For pharmaceuticals in order to evade Section 3(d), applicant should add sufficient data to prove enhance therapeutic efficacy/bioavailability add sufficient data to prove enhance therapeutic efficacy/bioavailability of the compound;of the compound;

EXAMINER’S ATTITUDE EXAMINER’S ATTITUDE

Pharmaceutical/chemical related applications when directed to Pharmaceutical/chemical related applications when directed to composition should give broad range of all ingredients followed by the composition should give broad range of all ingredients followed by the narrow ranges in sub-claim(s) with support in the specification;narrow ranges in sub-claim(s) with support in the specification;

Generally additional/new ingredient not supported by main claim Generally additional/new ingredient not supported by main claim should not be covered in the sub-claim;should not be covered in the sub-claim;

The range of the ingredients should be in weight/ weight, weight The range of the ingredients should be in weight/ weight, weight /volume and not be in milligram/milliliter, dosage forms are not allowed;/volume and not be in milligram/milliliter, dosage forms are not allowed;

Swiss type of claims and use claims not allowed and hence should be Swiss type of claims and use claims not allowed and hence should be avoided;avoided;

In case of process related claims, besides range of the ingredients, In case of process related claims, besides range of the ingredients, broad process parameters generally preferred in the main claim and broad process parameters generally preferred in the main claim and narrow range of the parameters may followed in sub-claim(s) with narrow range of the parameters may followed in sub-claim(s) with support in the specification;support in the specification;

Biosimilars in IndiaBiosimilars in India

According to the ABLE-PwC Report:According to the ABLE-PwC Report:

Consists primarily of Vaccines, Monocolonal antibodies, Consists primarily of Vaccines, Monocolonal antibodies, recombinant proteins and diagnostics recombinant proteins and diagnostics

Worth $1.9 billion in 2009-10Worth $1.9 billion in 2009-10

Biocon-Pfizer licensing deal – rights to commercialize Biocon’s Biocon-Pfizer licensing deal – rights to commercialize Biocon’s insulin biosimilars ($350 Million)insulin biosimilars ($350 Million)

Dr. Reddy’s LaboratoriesDr. Reddy’s Laboratories

2 biosimilars already marketed, including a biosimilar of rituxan2 biosimilars already marketed, including a biosimilar of rituxan

pipeline of 8 biosimilars, with two in clinical development stage.pipeline of 8 biosimilars, with two in clinical development stage.

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