Patentable and Non Patentable Biotech

Inventions

A Presentation By

D. Calab GabrielSenior Partner

K & S Partners, Gurgaon

Scope

• Patent Law

• What is non patentable

• Product patent

• Case studies –Product Patent

• Process Patent

• Case studies- Process Patent

Patent law

Patents Act 1970

Patentable inventionsany product or process which is :

• novel • not obvious to a person

skilled in the art• capable of industrial

application

WHAT IS NOT PATENTABLE? (section 3)

(d) New use of known substance/process

Polymorphs, esters, salts, combinations, derivatives that do not show enhanced therapeutic efficacy over known main substance

(e) Mere admixtures (as opposed in synergistic mixtures) and processes thereof

(i) Method of treatment of human beings/animals

(j) Plants, animals parts thereof

WHAT IS NOT PATENTABLE? (section 3)

Section 3(d)

3(d) 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 the mere discovery of any new property or new use for a known substance or of 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.

WHAT IS NOT PATENTABLE? (section 3)

Section 3(d) (cont.)

Explanation: For the purpose of this clause, salts, esters, ethers, polymorphs, metabolites, pure from, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy. Examples:

Toxic – non-toxic Stable – shelf life

WHAT IS NOT PATENTABLE? (section 3)

(e) a substance obtained by a mere admixture

resulting only in the aggregation of the

properties of the components thereof

WHAT IS NOT PATENTABLE? (section 3)

(i) any process for the medicinal / surgical / curative, prophylactic/diagnostic/therapeutic or other treatment of human beings or similar such process for treatment in animals.

IN VITRO methods?

(j) Plants and animals in whole or in part thereof other than microorganisms but including seeds, varieties and species and essentially biological processes for production or propagation of plants and animals.

Cell per se?

WHAT IS NOT PATENTABLE? (section 3)

SECOND MEDICAL USE

A FEW OF ACCEPTED CASES INSPITE OF 3(d) OBJECTION

S. no Application Nos. Section 3(d): Allowed different “Efficacy “subject matter.

1 2807/DELNP/2004(Salt)

Far better physiochemical properties i.e. Solubility, non hygroscopicity, distribution coefficient, formulation processability and photo-stability.

2 0844/DELNP/2005(Salt)

Better physiochemical Properties i.e. better photostability.

3 1046/CAL/1995(Polymorph,new form)

Better thermal Stability

4 INPCT/2002/00845(hydrate)

Better stability of heptahydrate over hydrate form

5 0457/KOLNP/2005(Derivative)

Enhanced Efficacy in Various test procedures and bioassays

6 0609/KOLNP/2003(Derivative)

Lesser Toxicity and better therapeutic Index

7 0482/KOLNP/2005(Polymorph)

More crystalline form to impart better thermodynamic stability, and purity

A FEW OF ACCEPTED CASES INSPITE OF 3(d) OBJECTION - contd

S. No Application Nos. Section 3(d): Allowed different “Efficacy “subject matter.

8 1342/KOLNP/2005(Derivative)

Improved oral Bioavailability

9 1180/MUMNP/2003(Complex)

Better stability, easily isolated and processed with minimal degradation.

10 656/DELNP/2005(Polymorph, new forms α-

and β- Form)

Form having better Stability under High temperature and relative humidity conditions

11 4719/DELNP/2005(Polymorph, new forms α-

and β- Form)

Forms having better Stability under High temperature and relative humidity conditions

12 30/DELNP/2003(Derivative)

Higher magnitude of biological activity against various cancer cells

13 842/DELNP/2005(Polymorph)

Higher stability (in terms of oral delivery)

14 1599/DELNP/2005(Derivative)

Higher pharmacotherapeutics properties like higher potency and significantly reduced brain access.

GLIVEC Test of 3(d) and the product patent regime.

Novartis AG filed patent application No. 1602/MAS/98

on July 17, 1998 for “crystal modification of A N-Phenyl-

2-Pyrimidineamine derivative, processes for its

manufacture and its use”

Specifically beta form of N-{5-[4-(4-Methyl-piperazino-

methyl)-benzoylamido]-2-methyl-phenyl}-4-(3-p yridyl)-2-

pyrimidine-amine salt.

( β form of methanesulfonic acid addition salt of a

pyrimidine compound and XRD pattern of β form was

provided)

GLIVEC

X-RD of Beta Form

Notable statement in specification “It goes without saying

that all the indicated inhibitory and pharmacological

effects of β form are also found with the free base”.

No enhanced efficacy shown

Established β form was pre-existing

Application was rejected by the Patent Office

Limited appeal to DB Chennai, case rejected

Limited issue before IPAB-case rejected

Challenged IPAB decision by way of write in SC

GLIVEC

TYPICAL BIOTECH INVENTION

Genomic DNA (plant)

Ligate

Protein product

Recombinant clone in plasmid vector

Micro-organism, variants

Patentable

Vector

PRODUCT PATENTS

All products of molecular biology: whether for use as drug or food product

Novel micro-organism (isolated/genetically engineered)

Novel gene and peptide sequences

Promoter, Marker

Novel cassette, construct

Vaccine

New viral strain

Micro-organisms

Not defined by Act

Possibly includes yeast, bacteria, recombinants, DNA

sequences, vectors

Are isolated microbes and colonies “mere

discovery” ??

Isolates, if characterized, deposited in ID and utility

found - patentable

Genetically modified organisms: patentable Source and origin of Biological material to be provided

in specification

Genes

Gene sequences if isolated and utility found,

patentable

Are they ‘part of animal or human being’ ?

Antibodies, including chimeric antibodies are

patentable

Nucleotide sequences

Nucleic Acids: molecules containing A, G, C and T residues (DNA); molecules containing A, G, C and U residues (RNA)

DNA is transcribed into RNA RNA is translated into Proteins Proteins are molecules containing up to 20 different

amino acid residues: A (ala), C (cys), D (asp), E (glu), F (phe), G (gly), H (his), I (ile), K (lys), L (leu), M (met), N (asn), P (pro), Q (gln), R (arg), S (ser), T (thr), V (val), W (trp)

3 nucleic acid residues code for one amino acid residue:

Isolated DNA: EP Position

What is a DNA sequence ? Can it be patented?

Held in RELAXIN CASE : Isolated DNA sequence is a chemical compound; can be patented

patentable An isolated and purified DNA molecule, RNA

molecule, or amino acid molecule isolated chemical compounds Full-Length Genetic Sequences patentable Corresponding amino acid sequence

patentable

Isolated DNA: US Position

US position- Contd

ESTs Partial nucleic acid sequences if proved

useful (eg: as encoding protein responsible for diagnosis of a specific disease) = patentable

DNA fragment encoding a full ORF May be useful if homology to existing nucleic acids or

proteins (with an established utility) is at least 95%

BOTTOM-LINE

Nucleotide sequences The sequence must be isolated and purified from its

natural environment raw sequences with no known use are not patentable

India: Product patent regime just introduced; So far few patents granted for nucleotide sequences Sequences patentable provided:

Isolated from natural surrounding Utility proven

BOTTOM-LINE

Nucleotide sequences

TTT ATT TGT CCT ATT TAA CCT CGT GCT CAT GCT phe ile cys pro ile stp pro arg ala his ala

Claim :

1.An isolated nucleic acid sequence bearing SEQ ID 1

Micro-organisms : EP position

EP case T396/93:Micro-organism includes bacteria, yeast, fungi, algae, protozoa, virus….Biotechnology Directive : Defines biological material not micro-organism Includes microbes, cell lines, viruses…. Excludes cell lines used for modifying germ line of

human beings

Micro-organisms : US position

Diamond v. Chakrabarty, 447 U.S. 303 (1980) genetically engineered bacteria are patentable “anything under the sun that is made by man”

Patents granted for : Yeast lines, Virus, hybridoma, oyester Harvard Mouse

Micro-organisms : Indian position

Section 3: Plants, animals and human beings except micro-

organism not patentable No distinction between isolated and genetically

modified micro-organism Many argue: Isolated micro-organism is no invention,

only GM

ISOLATED MICROORGANISM

Micro-organism Isolated ? Mutant ? Genetically modified ?

Deposit in international depository prior

to date of Indian filing

LIFE SCIENCES

Micro-organism Also describe source and origin of

biological material Bring out utility If mutated: set out conditions, details

CHARECTERISATION OF YEAST STRAIN

Ex: Mere mention of deposit of yeast strain in a

depository without setting out its characteristics

in the specification is “inadequate description”

Pfizer’s Application 1974 RPC 689

LIFE SCIENCES

DNA/Protein Sequences Describe fully how sequence was derived

If mutated, how? Utility/applications of sequence Products comprising sequence

Sequence listing to be submitted

USE OF NEW SUBSTANCE

A novel compound X useful for treatment of cancer

Use of compound X for treating cancer A novel compound X to prepare a

medicament Y for treating cancer Use of compound X to manufacture

medicament Y for management of cancer

BIO-PRODUCTS

Indicate the class and specific

chemicals used

Ex: All the oxidants that would enable the invention, all alkali/acids that would help to work the invention

EXAMPLE

What is claimed is:

1. The primers of SEQ ID NO: 1 and 2 useful for screening human beings for a pre-disposition to schizophrenia.

2. A method of screening human beings for a pre-disposition to schizophrenia by identifying non-sense mutation of codon TGG coding for amino acid tryptophan substituted with TAG, a non-sense codon, at nucleotide No. 825 from 5' end in exon 2 and its allelic variants in synaptogyrin 1 gene of chromosome 22q11-13, said method comprising:

(a) isolating DNA from blood leukocytes,

(b) amplifying isolated DNA by PCR using primers of SEQ ID NO: 1 and/or 2 of enclosed sequence listing, specific for exons of synaptogyrin 1 gene,

(c) sequencing the amplified DNA,

(d) comparing the sequenced DNA with that of normal synaptogyrin 1 gene,

(e) identifying the said mutation,

(f) designing oligonucleotide primer and/or probe of SEQ ID NO: 3 of enclosed sequence listing with its 3' end extending up to penultimate position of said mutation,

(g) screening for said non-sense mutation using primer and/or probe of step (f), and

(h) screening of said allelic variation for said non-sense mutation using appropriate allele specific oligonucleotide probes and/or primers selected from the group consisting of SEQ ID NO: 4 to 7 of enclosed sequence listing.

US PATENT NO. 6,764,824

US PATENT NO. 6,958,224

A chimeric protein αBNAC, of SEQ ID NO:2.

A chimeric protein as claimed in claim 1, wherein said chimeric protein

is consists of a total of 177 amino acids.

A chimeric protein as claimed in claim 1, wherein the net charge of

each unit of said chimeric protein is -5.

A chimeric protein as claimed in claim 1, wherein said chimeric protein

forms beta-sheet structure.

A chimeric protein as claimed in claim 1, wherein the N-terminal domain

of said chimeric protein contains nine proline residues.

What is claimed is:

1. A fermented fruit based herbal health drink composition useful as an antioxidant, cardio-tonic, diuretic, digestive, choleretic, nervine relaxant and immuno-modulant, comprising extract from plant Andrographis with concentration ranging between 0.5 to 10% in the total herbal health drink, extract from fruit, and ethanol ranging between 3 to 13% in the total herbal health drink, optionally extract from plant Tinospora and other additives.

US PATENT NO. 6,616,950

A biologically pure culture of Streptomyces sp. CIMAP

A.sub.1 strain bearing ATCC Accession No. PTA-4131

and capable of inhibiting the growth of phytopathogenic

fungi.

US PATENT NO. 6,558,940

1. A biological filter for the purification of waste gases, comprising a housing with at least one inlet and at least one outlet, and a bed of active micro-organisms contained in a carrier material consisting of pith extracted from coconut husks, the carrier material being provided in the housing such that the waste gases flowing in through the at least one inlet contact the bed of carrier material before exiting through the at least one outlet.

US PATENT NO. 6,696,284

1. A new and distinct high alkaloid producing Catharanthus roseus plant called `Dhawal` having NCIMB accession number 41147, and having the following combination of characteristics:

(a) plant height of 65-75 cm,

(b) light green to grayish green (emerald green 758/1 color designation from the "Horticultural Colour Chart II") pubescent leaves with distinctly undulating leaf margin,

(c) green stem,

(d) white flowers,

(e) field resistance to die back disease,

(f) high leaf yield of 1352 to 2557 kg/ha,

(g) 0.89 to 1.40% of total alkaloids in leaves,

(h) 1.60 to 2.22% of total alkaloids in roots,

(i) a randomly amplified polymorphic DNA (RAPD) profile distinct from the variety `Nirmal` when the DNA is polymerase chain reaction (PCR) amplified by four primers selected from the group consisting of: OPT 06, 09, 16 and 17, and

(j) higher herbage and alkaloid yield as compared to the variety `Nirmal`.

US PATENT NO. 6,548,746

PROCESS PATENTS

Any in vitro process

Method of protein purification,

downstream processing

Process using micro-organisms to

obtain chemicals

Screening Assays

Usually patentable Diagnostic assays: grey area

Is it ex-vivo or in-vivo? Does the result of the method indicate that

subject is suffering from a disorder? If yes, not patentable

Examples: PATENTABLE PROCESS

PCR process Process using microbe …

Novel fermentation products,

novel techniques

- RFLP, AFLP, fingerprinting etc

US PATENT 7247291 Nano sized sulfide compounds of cerium and a process for the preparation thereof

A bioprocess for the preparation of a sulfide compound of cerium, which comprises the steps of: a) treating trivalent Cerium salt, optionally in combination with 0.005-0.1%

w/v, of sodium sulfate, with a culture broth of sulfate-reducing bacteria (SRB), containing 0.05-1% v/v, of chloroform, under an inert atmosphere, at a temperature ranging between 25-40° C., at pH of 2 to 6 for a period in the range of 3 to 45 days in single or several installments such that a concentration of trivalent Cerium ions does not exceed 0.1% w/v at any point of time, to obtain a biomass,

b) concentrating the biomass as obtained in step a) at a temperature ranging between 60 to 150° C. for a period in the range of 1 to 6 hours to obtain a concentrated biomass, and

c) treating the concentrated biomass as obtained in step b) at a temperature between 600 to 1500° C. for a period in the range of 5 to 400 minutes followed by separation to obtain a sulfide of Cerium.

US PATENT 4960429

Chromium free process for the tanning of hides 

A chromium free process for the tanning of animal hides which includes, after the standard pretreatment of the hide, covalently modifying the skin collagen of said hide by a process ………..

U.S. PATENT 6777219

PROCESS FOR THE PREPARATION OF ALKALINE PROTEASE

  A process for the preparation of alkaline protease which

comprises growing a fungal strain Conidiobolus coronatus isolated from Anekal, Karnataka, India and deposited in American Type Cell Culture (ATCC) depository under Accession Number PTA-4132, in a medium having pH 6.0 to 9.0, a carbon source and a nitrogen source under aerobic conditions in submerged culture, at a temperature ranging between 20 to 30 C., for a period ranging between 2 to 6 days, harvesting the medium and separating the enzyme in liquid phase.

Australian Patent Application no: 2003217445

A method for unhairing animal skins or hides using a total lime and sulfide free enzymatic solution comprising:

• preparing an enzymatic solution from animal or plant tissue,• optionally presoaking of skins or hides in water at 10°C to 60°C

for 2 to 6 hours,• removing the soaking liquor,• applying the enzymatic solution by pasting or spraying on the

flesh side of the skin or hide and left for 10-24 hours at a temperature ranging between 10°C to 60°C, wherein the skins or hides are arranged flesh side to the flesh side or grain side to grain side,

• floating the skins or hides in liquid comprising the enzymatic solution, vi. removing

• the skins or hides from the liquid comprising enzymatic solution to produce an effluent and,

• unhairing of the skins or hides either by scraping the hair with a curved knife on a wooden beam or by an using unhairing machine.

Method for regeneration of organs

A method for regenerating organs in humans using: stem cells

from contiguous embryonic peritoneal layer

formation of mesodermal organs in vitro

avoids use of exogenous tissue

5 organs regenerated

Method for regenerating organs

Patent Act, 1970

sec 3(i) “any process for the medical,

surgical, …. treatment of human beings or

…render them free of disease ……”

invention in question hit by above provision

currently not patentable in India

US 6,227,202 obtained

Method for regeneration of organs

Ureter regenerated

?

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