Human Genome Sciences Inc. v Eli Lilly and Company

JurisdictionEngland & Wales
JudgeMr. Justice Kitchin
Judgment Date17 October 2008
Neutral Citation[2008] EWHC 2511 (Pat),[2008] EWHC 1903 (Pat)
Docket NumberCase No: HC06 C02687,Case No: HC06C02687
CourtChancery Division (Patents Court)
Date17 October 2008
Between:
Eli Lilly and Company
Claimant
and
Human Genome Sciences, Inc.
Defendant

[2008] EWHC 1903 (Pat)

Before :

The Honourable Mr Justice Kitchin

Case No: HC06C02687

IN THE HIGH COURT OF JUSTICE

CHANCERY DIVISION

PATENTS COURT

Royal Courts of Justice

Strand, London, WC2A 2LL

Mr Andrew Waugh QC and Mr Colin Birss (instructed by Howrey LLP) for the Claimant

Mr Simon Thorley QC and Mr Justin Turner (instructed by Powell Gilbert LLP) for the Defendant

Hearing dates: 7, 10–13, 17–21 December 2007, 11–12 and 15 January 2008

MR. JUSTICE KITCHIN :

Introduction

1

In this action the claimant (” Lilly”. applies to revoke European Patent (UK) 0,939,804 (”.he Patent”. held by the defendant (”.GS”.. I also have before me an application by HGS to amend the Patent, which is opposed by Lilly. The Patent discloses the nucleotide and amino acid sequence of a novel member of the TNF ligand superfamily which it calls Neutrokine-a. The application for the Patent was filed on 25 October 1996 and it was granted on 17 August 2005. It is currently under opposition in the EPO. Oral proceedings took place before the Opposition Division in June 2008 and the Patent was revoked, apparently on the basis that the claimed invention lacked any inventive step and constituted a claim to an arbitrary member of the TNF ligand superfamily without a known function. The Opposition Division declined to provide further reasoning during the oral proceedings and a written decision is awaited. HGS intends to file an appeal and the decision of the Opposition Division will be suspended in the meantime.

2

Neutrokine-a is known by many different names including TALL-1, xTNF4, THANK, BAFF and BLyS. The reason for this is that the same protein was found by separate groups and, in various publications around 1999, each group gave it a name based on either the origin or principal apparent function of the protein.

3

Neutrokine-a is a cytokine, that is to say a protein which acts as an inter-cellular mediator in inflammation and immune responses. By 1996, in the region of 100 cytokines had been cloned, sequenced and partially characterised and it was understood that they acted via cell membrane intermediary proteins called cytokine receptors. By that date a number of these receptors had also been identified and were known to be transmembrane proteins with the ability to bind cytokines outside the cell and cause metabolic changes inside the cell. The details of how cytokines and receptors acted were not well understood, but it seemed that they often had many different activities and that those activities frequently overlapped.

4

The first TNF cytokines to be identified were TNF-a (catechin) and TNF-ß (lymphotoxin), collectively “TNF”. TNF was originally thought to have an anti-tumour effect (hence its name Tumour Necrosis Factor) but it was subsequently discovered that its main activity was to cause inflammation by promoting the release of prostaglandins. This discovery generated a considerable interest in scientific and pharmaceutical communities. Many diseases are associated with inflammation and some, such as osteo arthritis, rheumatoid arthritis, chronic obstructive pulmonary disease, asthma, eczema and psoriasis, are very widespread. It was hoped that TNF would prove of immense value medically. It was also believed that other TNF proteins might exist which would also prove valuable. So researchers set about finding them. By 1996, a considerable number of similar ligands had been found and the TNF superfamily had taken shape. Some, such as TNF-a, TNF-ß and CD40L, had been highly studied and were known to have certain in vivo and in vitro activities. Others, such as CD27L, CD30L and 4–1BBL, were much less well understood.

5

One of the problems facing those researching into a human protein is how to obtain sufficient quantities of the protein to permit them to carry out their experiments. By the mid 1990s there was a well established way of trying to achieve this – the “wet lab” technique. The researcher would first identify the protein with the activity of interest, partially sequence it, determine the sequence of the nucleic acid that encoded it and then use that nucleic acid sequence as a probe to clone the actual gene from a library. The cloned gene could then be used to express large quantities of the protein in some suitable host cell. It is to be noted that the starting point of this work is the protein with the activity of interest.

6

In the early 1990s, other routes of investigation began to open up, based upon the emerging science of “bioinformatics” or “computational biology”. These relied upon the considerable increase in the amount of DNA and amino acid sequence data created and stored in publicly accessible databases and a parallel increase in the power of computers. As I shall elaborate, they permitted researchers to compare sequences and so identify genes and proteins of interest based upon their sequence similarity (homology) to other previously identified and characterised genes. But they suffer from the drawback that it may not be possible to determine the actual activity of the gene of interest until after it has been cloned and the protein has been subjected to in vitro and in vivo assays.

7

It was against this background that HGS found Neutrokine-a. It did so not by traditional wet lab techniques but by bioinformatics. Shortly after finding the polypeptide, it sought to protect its discovery by filing an application for patent protection which, in due course, led to the grant of the Patent. As proposed to be amended, it includes claims to the polypeptide, the nucleotide which encodes it, antibodies which specifically bind to it and corresponding claims to pharmaceutical and diagnostic compositions. The Patent identifies the polypeptide, correctly, as a member of the TNF ligand superfamily and includes a long description of its activities (which it defines as “Neutrokine-a activity”. and its uses. But that description is not supported in any way by any data obtained from in vitro or in vivo studies. It is essentially a prediction based upon what was known about other members of the TNF superfamily.

8

Lilly contends that that this prediction was wholly speculative and that HGS filed its application for patent protection without knowing the biological activity or function of Neutrokine-a, the identity of any receptor, the conditions which it causes or the diseases which it might be used to treat. This gives rise to the first of the fundamental attacks on the Patent and one which has received relatively little judicial consideration in this country. Lilly says that the specification fails to disclose an invention capable of industrial application.

9

For essentially the same reasons, Lilly says that the specification does not disclose the invention clearly enough and completely enough for it to be performed by a person skilled in the art. It contends that the alleged invention could not be put to any practical use without undue effort. But the insufficiency attack goes wider. Lilly contends that, quite irrespective of the position in relation to Neutrokine-a itself, the claims to specific antibodies and to therapeutic and diagnostic compositions are not enabled and too broad because they encompass such products for use in relation to a vast range of diseases and conditions, and for which the teaching in the specification is wholly inadequate. It says the scope of the claims far exceeds any technical contribution which HGS may have made.

10

HGS counters that this attack flies in the case of reality. The disclosure of a new member of the TNF family was a major contribution to medicine and the disclosures of the Patent were of outstanding potential value to the pharmaceutical industry. Moreover, the invention has given rise to therapies which are undergoing clinical trials. Indeed, HGS has been collaborating with GlaxoSmithKline to carry out clinical trials of a monoclonal antibody to Neutrokine-a called Lymphostat-ß for the potential treatment of rheumatoid arthritis and systemic lupus erythematosus (”.LE”.. For its part, Lilly has spent about $50 million developing a monoclonal antibody to Neutrokine-a and plans to spend another $250million bringing it to the clinic.

11

The second major attack on the Patent is one of obviousness. Lilly contends the claims are obvious over two items of prior art. The first is a polynucleotide clone called the “Image clone” which is said to have been have been made available to the public before the priority date on being sent by the Lawrence Livermore National Laboratory to Washington University for sequencing. The second is a polynucleotide sequence, referred to as the “Fujiwara EST”. which formed part of the GenBank library. Neither had been characterised but they both encode part of the full amino acid sequence of Neutrokine-a. Lilly contends that the application of standard bioinformatics techniques to either at the priority date would have led to Neutrokine-a and so they render the claims obvious.

12

The third attack on the Patent is one of added matter. It is made on the antibody claims and claims dependent upon them and it arises from an amendment made during the course of prosecution. Essentially it turns on a point of interpretation and I need say no more about it here.

13

I also have before me an application to amend the Patent. It is of some importance. The claims as granted are of considerable scope and HGS does not seek to defend them. They are directed not just to Neutrokine-a but also to other polypeptides encoded by polynucleotides which are homologous to the Neutrokine-a polynucleotide and which have Neutrokine-a activity. By the amendment HGS seeks to limit the claims to Neutrokine-a and to its extracellular domain. It also seeks to remove the reference to Neutrokine-a activity. Both...

To continue reading

Request your trial
32 cases
  • Eli Lilly and Company v Janssen Alzheimer Immunotherapy
    • United Kingdom
    • Chancery Division (Patents Court)
    • June 25, 2013
    ...at [11] the following summary of the relevant principles given by Kitchin J (as he then was) at first instance in the same case [2008] EWHC 1903 (Pat), [2008] RPC 29 at [239]: "The specification must disclose the invention clearly and completely enough for it to be performed by a person s......
  • Idenix Pharmaceuticals, Inc. v Gilead Sciences, Inc. and Others
    • United Kingdom
    • Chancery Division (Patents Court)
    • December 1, 2014
    ...at [11] the following summary of the relevant principles given by Kitchin J (as he then was) at first instance in the same case [2008] EWHC 1903 (Pat), [2008] RPC 29 at [239]: "The specification must disclose the invention clearly and completely enough for it to be performed by a person s......
  • Generics (UK) Ltd trading as Mylan v Warner-Lambert Company LLC
    • United Kingdom
    • Chancery Division (Patents Court)
    • September 10, 2015
    ...at [11] the following summary of the relevant principles given by Kitchin J (as he then was) at first instance in the same case [2008] EWHC 1903 (Pat), [2008] RPC 29 at [239]: "The specification must disclose the invention clearly and completely enough for it to be performed by a person s......
  • Autostore Technology as v Ocado Group Plc
    • United Kingdom
    • Chancery Division (Patents Court)
    • March 30, 2023
    ...point – which explains why nobody in real life ever did anything with it.” 402 In Eli Lilly & Co v Human Genome Sciences Inc. [2008] EWHC 1903 (Pat), Kitchin J (as he was then) said: “I accept that the skilled person must be deemed to consider any piece of prior art properly and in that se......
  • Request a trial to view additional results
3 firm's commentaries
  • The Basic Of Patent Law - Revocation, Non-Infringement And Clearing The Way
    • United Kingdom
    • Mondaq UK
    • April 13, 2017
    ...used in any kind of industry, including agriculture". The notion of industry is construed broadly (Eli Lilly v Human Genome Sciences [2008] EWHC 1903 (Pat)). Other exclusions The exclusions from patentability referred to anything which consists of (s1(2)): a discovery, scientific theory or ......
  • Life Sciences Newsletter, April 2009 - Part One
    • Canada
    • Mondaq Canada
    • May 21, 2009
    ...PROPERTY Industrial Application By Tracy Ko The English Patents Court case of Eli Lilly & Co v Human Genome Sciences Inc [2008] EWHC 1903 (Pat) gives guidance on requirement that an invention must have industrial application in order to be patentable. The case concerned a Human Genome S......
  • Patenting proteins: an Australian perspective
    • Australia
    • Mondaq Australia
    • June 17, 2020
    ...the claimed invention plausible and workable across the full scope of the claims. Footnotes 1Eli Lilly & Co v. Human Genome Sciences, Inc [2008] RPC 29, [239]. Evolva SA [2017] APO 57, 2 Evolva, [54]. 3 Warner-Lambert v. Generics (t/a Mylan) & Actavis [2018] UKSC 56. 4 The Australian Patent......
1 books & journal articles
  • Evidentiary Problems of Multidisciplinarity in the Litigation of Business Method Patents
    • Canada
    • Irwin Books Intellectual Property for the 21st Century: Interdisciplinary Approaches Interdisciplinarity in Practice
    • June 21, 2014
    ...other, even if, in fact, patents ac- 40 Human Genome Sciences Inc v Eli Lilly & Co, [2011] UKSC 51, rev’g [2010] EWCA Civ 33, af’g [2008] EWHC 1903 (Pat); Bilski, above note 2 at 3231. Evidentiary Problems of Multidisciplinarity in the Litigation of Business Method Patents • 453 tually have......

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