from blockbusters to biosimilars – the patent perspective

From blockbusters to biosimilars – the Patent Perspective

Dr. Thomas Friede Partner Patentanwalt & European Patent Attorney

2nd C5 Forum Biosimilars 2012

2nd C5 Forum Biosimilars 2012 2

Important biologics patents expire

Pharmaceutical Active ingredient Year of expiry

Lantus Insulin 2014

Remicade (infliximab) Monoclonal antibody 2014

Herceptin Monoclonal antibody 2014

NovoRapid/NovoLog Insulin 2014

Rituximab Monoclonal antibody 2014

Pegfilgrastim G-CSF 2015

Gardasil Vaccine (HPV) 2015

Synagis Monoclonal antibody 2015

Erbitux (Cetuximab) Monoclonal antibody 2016

Humira Monoclonal antibody 2018

Lucentis Monoclonal antibody 2018

Avastin Monoclonal antibody 2019


Biosimilars approved in EuropeBiosimilar Active ingredient Year of grantOmnitrope Somatotropin 2006

Valtropin Somatotropin 2006

Binocrit Epoetin Alpha 2007

Epoetin alpha Hexal Epoetin Alpha 2007

Abseamed Epoetin Alpha 2007

Retacrit Epoetin zeta 2007

Silapo Epoetin zeta 2007

Ratiograstim Filgrastim 2008

Biograstim Filgrastim 2008

Tevagrastim Filgrastim 2009

Filgrastim (Sandoz) Filgrastim 2009

Filgrastim Hexal Filgrastim 2009

Zarzio Filgrastim 2009

Nivestim Filgrastim 2010


Biosimilars under current review by EMA

Common name

Therapeutic area Number of applications

Originator product

Originator company

Filgrastim Immunostimulant (cancer/neutropenia)

1 Neupogen Amgen

Follitropin alpha

Sex hormones and modulators of the genital system (IVF)

1 Gonal-F Merck Serono

Infliximab Immunosuppressant (arthritis)

2 Remicade Merck/Johnson & Johnson

Insulin human

Diabetes 3 Humalog Eli Lilly

Total 7


Life cycle management - Evergreening First generation: product patent

Second generation: process patents, derivatives, formulations, different medical uses

Decision of the Enlarged Board of Appeal G2/08 confirms the patentability of dosage regime

However: DE Federal Supreme Court „Carvedilol II“ December 19, 2006

dosage regime cannot be considered for novelty inventive step

FR Decision of the Tribunal de Grande Instance Paris on September 28, 2010 „Actavis v. Merck“dosage regime feature violates Art. 53c) EPC


Life cycle management – Evergreening (II)

Separate prosecution of different aspects of the same invention in parent and divisional is desirable (compounds, modes of administration, medical indications)

However: T 307/03: Prohibition of double patenting even if the compound claimed in the parent is only encompassed by the scope of the divisional application

Solution: Introduction of a Disclaimer

Decision G 2/10 of the EPO Enlarged Board of Appeal, Point 4 of the Reasons: A disclaimer is not only admissible based on prior art under Art. 54(2) and 54(3) EPC but also in other situations such as for non-patentability related reasons


Industrial Applicability- The Principles (i) The patent must disclose "a practical application" and "some profitable use" for the claimed substance, so that the ensuing monopoly "can be expected [to lead to] some … commercial benefit" (T 0870/04, para 4, T 0898/05, paras 2 and 4);

(ii) A "concrete benefit", namely the invention's "use … in industrial practice" must be "derivable directly from the description", coupled with common general knowledge (T 0898/05, para 6, T 0604/04, para 15);

(iii) A merely "speculative" use will not suffice, so "a vague and speculative indication of possible objectives that might or might not be achievable" will not do (T 0870/04, para 21 and T 0898/05, paras 6 and 21);

(iv) The patent and common general knowledge must enable the skilled person "to reproduce" or "exploit" the claimed invention without "undue burden", or having to carry out "a research programme" (T 0604/04, para 22, T 0898/05, para 6)


Industrial Applicability (II)

(v) The absence of any experimental or wet lab evidence of activity of the claimed protein is not fatal (T 0898/05, paras 21 and 31, T 1452/06, para 5);

(vi) A "plausible" or "reasonably credible" claimed use, or an "educated guess", can suffice (T 1329/04, paras 6 and 11, T 0640/04, para 6, T 0898/05, paras 8, 21, 27 and 31, T 1452/06, para 6, T 1165/06 para 25);

(vii) Such plausibility can be assisted by being confirmed by "later evidence", although later evidence on its own will not do (T 1329/04, para 12, T 0898/05, para 24, T 1452/06, para 6, T 1165/06, para 25)


Broad claims

• disclosure of a concept fit for generalisation required1

Examiner has to substantiate reasons

why he believes the effect cannot be achieved →

objections may be based on common general

knowledge or prior art

no general rules

each case must be assessed on ist own merits2

1 T 435/91, OJ EPO 1995, 188.

2 See T 694/92, OJ EPO 1997, 408 concerning a plant patent.


Harmonization of national Case law with EPO Case law

UK Supreme Court HGS v Eli Lilly of November 2, 2011:

“In a number of recent decisions of the House of Lords, attention has been drawn to

"the importance of UK patent law aligning itself, so far as possible, with the

jurisprudence of the EPO (and especially decisions of its Enlarged Boards of

Appeal)", to quote Lord Walker in Generics (UK) Ltd v H Lundbeck A/S

[2009] UKHL 12; [2009] RPC 13, para 35.”

German Federal Supreme Court Xa ZB 10/09 of April 15, 2010:

(“Walzenformgebungsmaschine”):

“German courts have to comply with decisions handed down by the courts of the

European Patent Office or by courts in other EPC contracting states and which

essentially concern the same issue, and if necessary they have to address the

grounds which led to a divergent result in the prior decision.”

http://www.bailii.org/uk/cases/UKHL/2009/12.html

http://www.bailii.org/cgi-bin/redirect.cgi?path=/uk/cases/UKHL/2009/12.html


Scope of Biotech Patents

Scope of EP patents governed by Art. 69 EPC and protocol on the interpretation of Art. 69 EPC

However: Interpretation by national Case Law

Germany: - known for broad claim interpretation (function-oriented approach)- applying the doctrine of equivalents



The German Federal Supreme Court has developed three questions for the determination of equivalency:

1. Does the modified embodiment solve the problem underlying

the invention with means that have objectively the same technical effect?

2. Was the person skilled in the art, using his specialist

knowledge, able to find the modified means at the priority date as having the same effect?

3. Are the considerations that the person skilled in the art had to

apply oriented to the technical teaching of the patent claim in such a way that the person skilled in the art took the modified embodiment into account as being an equivalent solution?



Federal Supreme Court X ZB 12/00 of March 12, 2002 („Custodiol I“)

The indication of numerically defined ranges is generally binding. Figures outside the claimed range are not considered to be equivalent.

Exception from the rule: tolerances due to limits in working precision



Federal Supreme Court X ZR 16/09 of May 10, 2011 („Okklusionsvorrichtung“):

Where the description discloses several ways of achieving a

specific technical effect, as a rule, patent infringement by equivalent means is to

be denied if only one of these ways is incorporated in the claim.

Federal Supreme Court X ZR 69/10 of September 13, 2011 („Diglycidverbindung“):

at least two requirements would have to be met for infringement

under the doctrine of equivalence: (1) the specific effects of the variant are in

accord with the claimed solution, and (2) the variant differs from the

alternative merely outlined in the description but not in the claims in a similar

fashion as the claimed solution differs from it.


Recent Biotech Patent Decisions of German Courts – thermostable DNA polymerase OLG Düsseldorf of January 14, 2010 I-2 U 69/08

Claim 1 of the Patent relates to a thermostable DNA polymerase having a molecular weight of 86.000 to 90.000 Da as determined by SDS page.

The attacked embodiment: DNA polymerase having a molecular weight of 85.000 Da

The attacked DNA polymerase was found not to infringe the patent.

Court ruling: No equivalent infringement having regard to the Federal Supreme Court Schneidmesser and Custodiol decisions which rule that numerical ranges in claims are binding.


Recent Biotech Patent Decisions of German Courts – Ranibizumab

LG Düsseldorf of November 18, 2011 4a O 143/10: MedImmune vs. Novartis (Ranibizumab)

Representatives MedImmune: Johannes Heselberger, Thomas Friede

Litigation also in UK, FR, CH and NL

Claim 1 of the Patent relates to a method comprising Phage Display Technology

Ranibizumab is a Fab fragment specific for VEGF used for the treatment of AMD (age-related macula degeneration)

Annual Ranibizumab sales (Europe): US-$ 1.3 billion

Patent found to be infringed by import and sale of immediate product of the process


Recent Biotech Patent Decisions of German Courts - Ranibizumab

Ranibizumab differs from the binding molecule actually obtained by the process by several substitutions introduced after the phage display step.

However:

Claim covers binding molecule, fragment or derivative with binding specificity for the target

=> Claim encompasses Ranibizumab.


Recent Biotech Patent Decisions of German Courts - Ranibizumab

Narrowing claim construction by the Defendants:

The Defendants argued that the core of the invention resides in a screening method which does not generate a product.

Court reasoning:

The claimed method is a manufacturing method since it comprises manufacturing steps.


Thank you for your attention !

Questions?

Dr. Thomas Friede BARDEHLE PAGENBERG

Prinzregentenplatz 7 81675 München

[email protected] www.bardehle.com

from blockbusters to biosimilars – the patent perspective

Documents

commercial benefit t

patent perspective

common general knowledge

profitable use

speculative use

enlarged board of appeal

different medical usesdecision

process patents