Transcript Intellectual Property, Bioprospecting and Traditional

Patentable and Non Patentable
Biotech Inventions
A Presentation
By
D. Calab Gabriel
Senior 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 inventions
any 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?
WHAT IS NOT PATENTABLE?
(section 3)
(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?
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 βForm)
Form having better Stability under High temperature and relative humidity conditions
11
4719/DELNP/2005
(Polymorph, new forms α- and βForm)
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-Phenyl2-Pyrimidineamine derivative, processes for its
manufacture and its use”
Specifically beta form of N-{5-[4-(4-Methyl-piperazinomethyl)-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
GLIVEC

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
TYPICAL BIOTECH INVENTION
Genomic DNA
(plant)
Vector
Ligate
Recombinant clone in plasmid
vector
Protein product
Micro-organism, variants
Patentable
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
Isolated DNA: US Position
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
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 microorganism 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
US PATENT NO. 6,764,824

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 nonsense 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. 6,958,224
 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.
US PATENT NO. 6,616,950
 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. 6,558,940
 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. 6,696,284
 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. 6,548,746
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`.
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
?