Transcript Slides-Patenting Biotechnology Around the Globe

Patenting Biotechnology in Japan
and recent hot issues
AIPLA Mid-Winter Meeting
January 25, 2012
Ayako Kobayashi
TMI Associates
Summary




Patenting stem cells
Patenting antibodies
New Examination Guidelines for applications
for Patent Term Extension
Regulations for Biosimilars
Patenting stem cells

Novelty - Inherent features of the prior art cell

How to specify new cells






expression profile of surface markers
origin
morphology
preparation method
functions (e.g., “differentiating into XXX.”)
Do the Inherent expression or functions of
the prior art cells destroy the novelty of the
claimed cells?
Patenting stem cells

Novelty - Inherent features of the prior art cell

In many cases, the JPO Examiners do not consider the
inherent features of the prior art cell.

Rejected Example (JP2007-200588)
Claim 1: An isolated adipose-derived stem cell having a marker
profile comprising a combination of STRO-01+, CD49d+, and low
or undetectable levels of CD106.
The Examiner and Appeal Board denied the novelty, citing
a reference that failed to mention the expression profile of
surface markers when the inventors and the authors of the
prior art overlapped.
Patenting stem cells

Novelty – Product-by-process claims


The technical scope of a product-by-process claim is NOT
limited to the product produced by the process recited in
the claim.
Example
Claim: An induced pluripotent stem cell obtained by introducing
genes Oct3/4, Klf4, …into a somatic cell.
The Examiner denied the novelty of iPS cells, citing a
reference of ES cells, because:
- the ES cells expressed the same surface markers as iPS
cells.
- the claimed cells possibly contained cells in which
transgene has been spontaneously deleted.
Patenting stem cells

Inventive step


The requirement for inventive step does not appear to be
high.
Sometimes an advantageous effect compared to the prior
art cells is required.
Patenting stem cells

Enablement requirement



Very strict.
Functional claims are likely to be rejected.
The Examiners often require to limit the scope of the
invention to the level of the working examples.
Patenting stem cells

Enablement requirement

Would an enablement rejection be overcome by submitting
additional data?


It is more likely that the Examiners will take later-submitted
data into consideration in situations where they have already
formed an impression that the enablement requirements are
satisfied for part of the claimed invention, and the latersubmitted data is used to furnish the examples necessary to
show that the enablement requirements have also been
satisfied for the remainder of the claimed invention.
When the original specification fails to include any
experimental data, it is almost impossible to overcome an
enablement rejection by submitting additional data.
Patenting stem cells

Public order, etc.

Article 32
An invention liable to contravene public order, morality or
public health shall not be patented...

When an invention includes a step of destroying an embryo,
it will be rejected under Article 32.

An invention of culturing or differentiating method of an
already-established ES cell line would be acceptable.
Patenting stem cells

Stem cell-related patent rights

To date, there have been no precedents regarding the
patentability or infringement of a stem cell-related invention.
Thus, the following issues, for example, remain unresolved:


Does the inherent feature of the prior art cells really not
destroy the novelty of the claimed cells?
Would practicing an ES cell-related invention using iPS cells
constitute infringement under the Doctrine of Equivalents?
Patenting Antibodies

When the antigen is known, it is necessary to specify the
new antibody using its special features and show that the
antibody produces an advantageous effect compared to
the prior art.

When the antibody is not sufficiently specified, the
Examiner will reject the application due to:
 lack of inventive step and/or
 failure to comply with the enablement and support
requirements.
Patenting Antibodies

How to specify a new antibody







CDR sequences – Successful, but the sequences of all six
CDRs should be specified
>90% homology of CDR sequences – Not successful
Substitutions in CDR sequences – Not successful
CDR sequences of either Heavy Chain or Light Chain – Not
successful
Dissociation Constant (Kd) – Not successful
Sister clone obtained from the same hybridoma – Not
successful
Epitope sequences – Successful in many cases
Patenting Antibodies

Recent Examples (1)

JP4818107
An isolated antibody or its antigen-binding fragment which
specifically binds to the epitope consisting of amino acids 86 to 111
set forth in SEQ ID NO:46.

JP4799863
A pharmaceutical composition that inhibits cancerous growth of
cells comprising an antigen or its antigen binding site, wherein the
antigen or its antigen binding site binds to an epitope located within
position 200 to 400 of EphB4 (SEQ ID NO:1), and wherein the
epitope comprises GSCVV.
Patenting Antibodies

Recent Examples (2)

JP4818107
A monoclonal antibody or its Fab fragment, capable of binding to
mouse VEGF and human VEGF with Kd values within 10 fold of
the other, and is capable of inhibiting the binding of VEGF to a
VEGF receptor, and recognizes an epitope comprising residues
F17, I83 and Q89 of human VEGF.
Patenting Antibodies

Recent Examples (3)

JP4637480
An isolated antibody consisting of a heavy chain variable region
and a light chain variable region, wherein:
the heavy chain variable region consists of the amino acids set
forth in SEQ ID NO:11 that may comprise 3 or less amino acid
substitutions;
the light chain variable region consists of the amino acids set forth
in SEQ ID NO:12 that may comprise 2 or less amino acid
substitutions; and
the antibody specifically binds to Ang-1 and Ang-2.
Patent Term Extension (“PTE”)

More than one PTEs may be granted based on more than one
marketing approvals for the same active ingredient in Japan.

The JPO had previously rejected applications for a PTE based on the
latter of the two marketing approvals in situations where the former
approved drug and the latter approved drug contained the same
active ingredient, and were directed to the same disease, even though
there were differences in dose or formulation between the two drugs.

Under the new guidelines, the Examiner will compare the former
approval and the latter approval in terms of the features recited in the
claims, in addition to the active ingredient and the subject disease.
When all such features are in common between the former and the
latter approval, an application for a PTE based on the latter approval
would be rejected.
Patent Term Extension

Examples
Claim 1: A painkiller containing compound A.
Former Approval: A painkiller in a tablet form containing 5mg of
compound A.
Latter Approval (i): A painkiller in an injectable form containing 5mg of
compound A.
Latter Approval (ii): A painkiller in a tablet form containing 10mg of
compound A.
Under Old and New Guidelines
An application for a PTE based on latter approval (i) or (ii) would be
rejected.
Patent Term Extension

Examples
Claim 1: A painkiller in an injectable form containing compound A.
Former Approval: A painkiller in a tablet form containing 5mg of
compound A.
Latter Approval (i) : A painkiller in an injectable form containing 5mg of
compound A.
Latter Approval (ii) : A painkiller in a tablet form containing 10mg of
compound A.
Under Old Guidelines
Applications for a PTE based on the latter approvals would have been
rejected.
Under New Guidelines
An application for a PTE based on latter approval (i) would not be
rejected, while latter approval (ii) would be rejected.
Patent Term Extension

Examples
Claim 1: A painkiller comprising compound A.
Claim 2: A painkiller according to claim 1 which is in a tablet form.
Former Approval: A painkiller in an injectable form containing compound A.
Latter Approval : A painkiller in a tablet form containing compound A.
Only claim 1 would be considered.
Under New Guidelines
An application for a PTE based on the latter approval would be rejected.
Patent Term Extension

Examples
Patent 1: A painkiller comprising compound A.
Patent 2: A painkiller in a tablet form comprising compound A.
Former Approval: A painkiller in an injectable form containing compound
A.
Latter Approval : A painkiller in a tablet form containing compound A.
Under Old Guidelines
An application for a PTE based on the latter approval would have been
rejected for both patents 1 and 2.
Under New Guidelines
An application for a PTE based on the latter approval would be rejected
for patent 1 but would not be rejected for patent 2.
Biosimilars

“Guidelines for the Quality, Safety and Efficacy Assurance of
Biosimilars” and “Handling of nonproprietary and brand names of
Biosimilars” were issued by the MHLW in March 2009.
The English translation made by Pharmaceutical Research and Manufactures of
America can be obtained at:
http://www.phrma-jp.org/archives/pdf/others/PFSBELD%20Notification%20of%20Handling%20of%20names%20of%20follow-on%20biologics_No.%200304007.pdf
http://www.phrma-jp.org/archives/pdf/others/PFSBELD%20Notification%20of%20Handling%20of%20names%20of%20follow-on%20biologics_No.%200304011.pdf

The first Application for the Marketing Approval for Biosimilar (G-CSF)
was filed on December 26, 2011.
Thank you!
Ayako Kobayashi
TMI Associates
[email protected]