Eli Lilly and Company v Janssen Alzheimer Immunotherapy

JurisdictionEngland & Wales
CourtChancery Division (Patents Court)
JudgeMr Justice Arnold
Judgment Date25 June 2013
Neutral Citation[2013] EWHC 1737 (Pat)
Date25 June 2013
Docket NumberCase No: HC11C03400

[2013] EWHC 1737 (Pat)

IN THE HIGH COURT OF JUSTICE

CHANCERY DIVISION

PATENTS COURT

Royal Courts of Justice, Rolls Building

Fetter Lane, London, EC4A 1NL

Before:

The Hon Mr Justice Arnold

Case No: HC11C03400

Between:
Eli Lilly and Company
Claimant
and
Janssen Alzheimer Immunotherapy
Defendant

Andrew Waugh QC and Thomas Mitcheson (instructed by Simmons & Simmons) for the Claimant

Simon Thorley QC and Charlotte May (instructed by Linklaters LLP) for the Defendant

Hearing dates: 24 26, 29 30 April, 1, 3 May 2013

Approved Judgment

I direct that pursuant to CPR PD 39A para 6.1 no official shorthand note shall be taken of this Judgment and that copies of this version as handed down may be treated as authentic.

Mr Justice Arnold Mr Justice Arnold

Contents

Topic

Paragraphs

Introduction

1

The witnesses

2–9

Lilly's witnesses

2–4

JAI's witnesses

5–9

Technical background

10–105

The structure of the brain

12–18

The cells of the brain

19–21

Amyloidosis

22–23

AD

24–30

31–38

Transgenic mouse models

39–41

Approaches to the treatment of AD

42

Blood-brain barrier

43–46

Innate and adaptive immunity

47–51

Phagocytosis

52–54

Antigen-Presenting Cells

55–57

T cells

58–62

B cells

63–70

The structure of antibodies

71–75

Antibody classes or isotypes

76–80

Fc receptor-mediated phagocytosis

81–84

The complement pathways

85–86

Antibody-dependent cellular cytotoxicity (ADCC)

87–88

Plasma half-life of antibodies

89

Monoclonal antibodies

90–95

Active and passive immunisation

96–105

The Patent

106–149

Background

107–109

Summary of the claimed invention

110

Definitions

111

Detailed description

112–121

I General

113

II Therapeutic Agents

114–117

III Patients Amendable to Treatment

118

IV Treatment Regimes

119–120

V Diagnosis

121

Examples

122–149

I Prophylactic Efficacy of Aβ Against AD

123–126

II Dose Response Study

127

III Screen for Therapeutic Efficacy Against Established AD

128–136

IV Screen of Aβ Fragments

137–139

V Preparation of Polyclonal Antibodies for Passive Protection

140

VI Passive Immunization with Antibodies to Aβ

141–143

VII Comparison of Different Adjuvants

144

VIII Immunse Responses to Different Adjuvants in Mice

145

IX Therapeutic Efficacy of Different Adjuvants

146

X Toxicity Analysis

147

XI Prevention and Treatment of Subjects

148–149

The claims

150

The skilled team

151–153

Common general knowledge

154–161

Terminology with regard to Aβ

156

Methods for assisting the passage of antibodies across the BBB

157–159

Effect of CFA on the BBB

160

Aβ as a target for AD research

161

Matters that were not common general knowledge

162–168

The Schenk Paper

163–166

DeMattos 2001 and the peripheral sink hypothesis

167–168

Construction

169–206

Immune response

171–181

An antibody to Aβ

182–189

For use in preventing or treating a disease characterised by amyloid deposit in a patient

190–204

Aggregated Aβ

205

Dissociated Aβ

206

Added matter

207–217

Disclosure of an antibody which does not induce an immune response

209–215

Disclosure of an antibody that is of the human IgG1 isotype

216–217

Novelty

218-

Konig

220–226

Disclosure of human IgG1?

227–229

Disclosure of efficacy?

230

Obviousness

231–247

The law

231–233

Obviousness of claim 1 over Konig

234–245

Obviousness of claim 1 over Becker

246

Agrevo obviousness

247

Insufficiency

248–313

The law

248–257

Classical insufficiency

250

Excessive claim breadth

251

Post-dated evidence

252–257

The facts

258–313

Is it plausible?

259–271

Can the invention be performed without undue burden?

272–297

Is the claim of excessive breadth?

298–313

Infringement

314–353

Is solanezumab specific for monomeric Aβ?

319–343

Does solanezumab which crosses the BB induce any downstream effects?

344

Does solanezumab affect the equilibrium in the brain?

345–348

Does solanezumab induce FcRn-mediated clearance?

349–353

Summary of main conclusions

354

Introduction

1

The Defendant ("JAI") is the proprietor of European Patent (UK) No. 1 994 937 ("the Patent") entitled "Prevention and treatment of amyloidogenic disease". The Patent discloses and claims pharmaceutical compositions comprising an antibody to β-amyloid peptide, also referred to as amyloid-β or Aβ. The Patent is one of four patents granted pursuant to divisional applications from a parent application which matured into EP 1 033 996. The Claimant ("Lilly") seeks an order for revocation of the Patent and a declaration that dealings in pharmaceutical compositions comprising an antibody called solanezumab, which Lilly currently has in Phase 3 development for the treatment of Alzheimer's Disease ("AD"), will not infringe the Patent. Lilly attacks the validity of the Patent on the grounds of added matter, lack of novelty, obviousness, and insufficiency. There is no challenge to the claimed priority date of 2 December 1997. JAI has applied to amend the Patent by deleting claims 13, 14 and 15 and by omitting two words from claim 11. That application is unopposed.

The witnesses

Lilly's witnesses

2

Lilly called a single expert witness, Professor Thomas Wisniewski. Prof Wisniewski has been Professor of Neurology, Pathology and Psychiatry at New York University ("NYU") School of Medicine since 2005. He obtained an MBBS from King's College London ("KCL") in 1983. He moved to New York in 1984 to pursue his interest in neurodegenerative research. Having completed residences in Anatomical Pathology, Neurology and Neuropathology at NYU Medical Center and Columbia University, in 1990 he took up an academic position as Clinical Instructor in Neurology at NYU. From 1990 to 1994 he worked with the immunologist Professor Blas Frangione. He became an Assistant Professor of Neurology and Pathology in 1992 and a tenured Assistant Professor of Neurology, Pathology and Psychiatry in 1999. He has been Director of the Conformational Disorders Laboratory at NYU since 1997 and Director of the Neuropathology Core of the NYU AD Center since 2002. He has held a number of other academic and hospital appointments. These positions allow him to divide his time equally between treating patients and research. His research focuses on neurodegenerative disorders, in particular the pathogenesis and treatment of AD and prion-related diseases. He has been on the editorial boards of several academic journals. He has published 217 full length peer-reviewed publications. He has won a number of awards. He is a named inventor on a number of patents. He was an investigator in the Phase 3 trials of both JAI's product bapineuzumab and Lilly's product solanezumab.

3

Prof Wisniewski had expertise in neuroscience, immunology and clinical treatment. Counsel for JAI rightly accepted that Prof Wisniewski was both highly expert and gave his evidence clearly and fairly, but submitted that on some points Prof Wisniewski had had difficulty in putting himself in the position of the addressee of the Patent rather than viewing matters from his own perspective. I think there is some force in this, and I have taken this into account when assessing his evidence.

4

In addition, Lilly adduced unchallenged factual evidence from Dr Ronald DeMattos. He obtained a PhD in Molecular and Cellular Biochemistry from the State University of New York at Stony Brook in 1998. From October 1998 to June 1999 he held a post-doctoral position at Stony Brook. From June 1999 to 2002 he held a post-doctoral position in David Holtzman's laboratory at Washington University School of Medicine. In September 1999 he received funding for a project to analyse physiologically relevant apolipoprotein/Aβ interactions in mouse models of AD. This work led first to the filing of US Patent Application 60/184601 in February 2000 (and later to further patent applications) and secondly to the publication of DeMattos et al, "Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases Aβ burden in a mouse model of Alzheimer's disease", PNAS, 98(19), 8850–885 (2001) ("DeMattos 2001") on 17 July 2001. This was the starting point for the development of solanezumab. In late 2002 Dr DeMattos joined Lilly, where he is now a Research Fellow in Neuroscience Discovery Research. In his witness statements Dr DeMattos described aspects of the development of solanezumab.

JAI's witnesses

5

JAI called two expert witnesses, a neuroscientist, Professor Paul Francis, and an immunologist, Dr Michael Owen. Prof Francis is Professor of Neurochemistry at KCL. He obtained a BSc in Physiology and Biochemistry from the University of Reading in 1979 and a PhD in Neuroscience from the same institution in 1984. From 1982 to 1990 he was a Post-Doctoral Research Fellow and from 1990 to 1995 an Honorary Lecturer at the Institute of Neurology, Queen Square. In 1995 he became Senior Lecturer in Biochemistry and Molecular Biology at the United Medical and Dental Schools of Guy's and St Thomas' Hospitals, which merged with KCL in 2000. He was appointed Reader in 2004 and Professor in 2008. In 2008 he also became Director of Brains for Dementia Research. He is the author of over 122 publications in refereed journals. His research includes work on the mechanisms of AD and other types of dementia, such as frontotemporal dementia, Lewy body dementias and vascular dementia. He has been involved in some clinical trials relating to AD, in particular a trial of memantine in people with Down's syndrome.

6

As counsel for Lilly pointed out, Prof...

To continue reading

Request your trial
5 cases
  • Merck Sharp & Dohme Ltd v Ono Pharmaceutical Company Ltd and Another
    • United Kingdom
    • Chancery Division (Patents Court)
    • 22 October 2015
    ...specificity to the agent claimed (for example: Idenix v Gilead at paragraphs 444–462 and Eli Lilly v Janssen Alzheimer Immunotherapy [2013] EWHC 1737 (Pat) paragraphs 259–271). On the other hand the material relied on must make the particular claimed use, whatever it is, plausible. In HGS ......
  • Generics (UK) Ltd (trading as Mylan) v Richter Gedeon Vegyeszeti Gyar RT
    • United Kingdom
    • Chancery Division (Patents Court)
    • 22 May 2014
    ...I did not find at all persuasive the analogies drawn by Mr Acland QC for the Claimant with cases reviewed by Arnold J in Eli Lilly v Janssen Alzheimer Immunotherapy [2013] EWHC 1737 (Pat); [2014] RPC 1 at [190]–[204], in which the words "for treating cancer" were found to mean only "has a ......
  • Eli Lilly and Company v Janssen Sciences Ireland UC (formerly Janssen Alzheimer Immunotherapy)
    • United Kingdom
    • Chancery Division (Patents Court)
    • 18 February 2016
    ...a claim for a DNI in respect of solanezumab. The UK parent patent was held to be invalid in a judgment of Arnold J in June 2013: [2013] EWHC 1737 (Pat). His conclusions on the issues before him were: i) the parent patent was not invalid on the grounds of added matter; ii) claim 1 in the pa......
  • Astex Therapeutics Ltd v Astrazeneca AB
    • United Kingdom
    • Chancery Division
    • 21 June 2017
    ...50 Much of the general technical background is set out in my judgment in Eli Lilly and Co v Janssen Alzheimer Immunotherapy [2013] EWHC 1737 (Pat) at [12]–[42], which Dr Hill referred to in his first report and which I will take as read. As Dr Hill noted, those passages considered the posit......
  • Request a trial to view additional results

VLEX uses login cookies to provide you with a better browsing experience. If you click on 'Accept' or continue browsing this site we consider that you accept our cookie policy. ACCEPT