Hospira UK Ltd v Cubist Pharmaceuticals LLC

JurisdictionEngland & Wales
CourtChancery Division (Patents Court)
JudgeMr Justice Henry Carr
Judgment Date10 June 2016
Neutral Citation[2016] EWHC 1285 (Pat)
Docket NumberCase No: HP-2014-000037
Date10 June 2016

[2016] EWHC 1285 (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 Henry Carr

Case No: HP-2014-000037

Between:
Hospira UK Limited
Claimant
and
Cubist Pharmaceuticals LLC
Defendant

Richard Meade QC and Isabel Jamal (instructed by Taylor Wessing LLP) for the Claimant

Andrew Waugh QC, Thomas HinchliffeQC andStuart Baran (instructed by Carpmaels & Ransford LLP) for the Defendant

Hearing dates: 21, 22, 25–29 April, 3, 5 and 6 May 2016

Introduction

5

The issues

5

The 417 Patent

5

The 179 Patent

6

The 047 Patent

6

All Patents

6

The 417 Patent

7

The witnesses in respect of the 417 Patent

7

Dr Ebert

7

Dr Harding

8

Dr Zeckel

9

The Skilled Addressee

10

Lilly's development history of daptomycin

10

Conclusion in relation to the Lilly daptomycin trials

14

Dr Zeckel's knowledge and Cubist's disclosure

15

Common general knowledge

16

Vancomycin and the need for new treatments for gram-positive infections

16

Common general knowledge/what would have been found out about the Lilly trials

17

Skeletal muscle toxicity

21

Tolerance of side effects

22

Advantages of once-daily dosing

22

Concentration dependent killing

23

Aminoglycosides and quinolones

24

Post-antibiotic effect ("PAE")

25

The pharmacokinetic and pharmacodynamic properties of daptomycin

25

Paediatric dosing

26

The 417 Patent

26

The Claims

29

Scope of the claims

30

Legal principles and the effect of G 2/98

30

Disclosure of the first priority document

33

The second priority document

36

The Cubist Press Release

37

Disclosure

37

Anticipation by the Cubist Press Release

37

Obviousness in light of the Cubist Press Release

38

Legal principles

38

Application to the facts

39

Woodworth

42

Disclosure

42

Anticipation by Woodworth

44

Obviousness in light of Woodworth

44

Added matter/lack of clarity

46

Legal principles

46

Application to the facts

47

Sufficiency – enablement across the full width of the claims

48

The Purity Patents

48

The witnesses in respect of the purity patents

48

Dr Baker

48

Prof Myerson

49

Dr Kelleher

50

The skilled addressee

50

Whether a clinician would be included in the skilled team

51

The relevance of the scale of the purification processes

51

The 179 Patent

52

The evidence of Dr Kelleher

52

Dr Kelleher's first statement

52

Dr Kelleher's cross-examination

54

Common general knowledge of relevance to the 179 Patent

56

Purity versus yield

56

Fermentation and clarification

57

Purification processes

57

Multiple purification steps and modes

57

AEC

58

Purification techniques used on lipopeptides

58

HIC and lipopeptides

59

The use of AEC in combination with HIC

59

The use of buffers and chaotropic agents

60

Daptomycin

61

Anhydro daptomycin and the β isomer of daptomycin

61

The specification of the 179 Patent

63

The claims of the 179 Patent as granted

66

The disclosure of US 843

68

Obviousness over US 843

69

Motivation to improve US 843

71

Use of AEC

71

AEC as the first step

72

HIC followed by AEC

72

Use of buffers and chaotropic agents

72

Fair prospect of success

72

The secondary evidence

73

Conclusion

73

Obviousness of the 179 Patent over common general knowledge alone

73

Added matter

74

Legal principles

74

The starting sample of daptomycin and obtaining "purified daptomycin" in combination with the purification steps of claim 1

75

Claim 1 – list of chaotropic agents

77

Claim 3 – "purified daptomycin"

77

Enablement across the full width of the claims

78

The 047 Patent

78

The skilled team

78

Additional common general knowledge of relevance to the 047 Patent

78

Surfactants

78

Lipopeptides as surfactants

79

Primary structure of lipopeptides

79

Daptomycin as a surfactant

80

Tests to determine whether a lipopeptide is a surfactant

80

Common general knowledge of surfactin at the priority date

81

Formation of micelles

81

The specification of the 047 Patent

82

Claim 1 of the 047 Patent

83

The disclosure of Lin & Jiang

84

Obviousness of the 047 Patent in the light of Lin & Jiang

84

Purification of surfactin and daptomycin

84

Manipulating the CMC by altering the pH

86

Assessment of obviousness in the light of Lin & Jiang

86

Conclusions

90

Mr Justice Henry Carr

Introduction

1

The Claimant ("Hospira") seeks revocation of three patents ("the Patents") owned by the Defendant ("Cubist"), namely:

i) EP (UK) 1,115,417 ("the 417 Patent");

ii) EP (UK) 1,252,179 ("the 179 Patent"); and

iii) EP (UK) 2,264,047 ("the 047 Patent").

2

All three patents concern the antibiotic daptomycin, which was originally discovered by Eli Lilly ("Lilly") in the 1980s. Daptomycin is a lipopeptide, and lipopeptides are molecules consisting of a lipid (a naturally occurring molecule such as a fat) connected to a peptide (a short chain of amino acids).

3

Cubist has made an unconditional application to amend the 417 Patent. References to the claims of the 417 Patent in this judgment are to the proposed amended form. The 417 Patent claims a dosage regimen for daptomycin of between 3–10 mg/kg administered once every 24 hours, for treating a bacterial infection. It has a first claimed priority date of 25 September 1998 and a second claimed priority date of 24 March 1999. The 417 Patent was filed on 24 September 1999. The 179 and 047 Patents concern purification processes for daptomycin (collectively "the Purity Patents"). They rely upon the same priority documents and their earliest claimed priority date is 20 January 2000.

4

The validity trial of all three patents was heard at the same time. This did not prove easy, either for the parties' legal representatives or for the court. The 417 Patent raised different issues and involved evidence from different experts to the Purity Patents. It would have been preferable to hear the trial of the 417 Patent first, followed shortly afterwards by the trial of the Purity Patents. Generally speaking, three patents with different subject matter are likely to prove too many for a single trial.

5

To date, none of the Patents has enjoyed a happy life. The US equivalent of the 417 Patent was held to be anticipated by and obvious over prior art relied on in these proceedings. US patents with common features to the Purity Patents (although not identical claims) were also held to be invalid over prior art relied on in these proceedings. Those decisions were affirmed on appeal. The Opposition Division of the EPO held that the 417 Patent was not entitled to its first priority date and was invalid for lack of inventive step. The decision of the Opposition Division is under appeal to the Technical Board of Appeal. However, I have heard different evidence and different arguments, and in respect of the US judgments, I am applying a different system of law. Other than passages to which I expressly refer, I have not relied on those decisions.

The issues

The 417 Patent

6

The following grounds of invalidity are relied upon by Hospira:

i) That the 417 Patent is not entitled to either of its claimed priority dates. Cubist accepts that if the 417 Patent is not entitled to either its first or second claimed priority dates, then it is invalid.

ii) That, as a result of non-entitlement to the first priority date, the 417 Patent is anticipated or rendered obvious by a Press Release published on 1 March 1999 ("the Cubist Press Release").

iii) Irrespective of the priority attacks, that Woodworth et al., Single-Dose Pharmacokinetics and Antibacterial Activity of Daptomycin, a New Lipopeptide Antibiotic, in Healthy Volunteers, Antimicrobial Agents and Chemotherapy (1992) ("Woodworth") anticipates the 417 Patent or deprives it of inventive step.

iv) That the claims as proposed to be amended add matter over the application as filed and claim 2 as proposed to be amended lacks clarity.

v) That the claims of the 417 Patent are not enabled across their full width. This is advanced as a squeeze with the attacks based on the prior art.

The 179 Patent

7

The following grounds of invalidity are relied upon by Hospira:

i) That the 179 Patent lacks inventive step over US 4,874,843 ("US 843").

ii) That the 179 Patent lacks inventive step over the common general knowledge alone and/or is a non-inventive collocation of known purification steps.

iii) That the claims of the 179 Patent add matter over the application as filed.

iv) That the claims of the 179 Patent are not enabled across their full width. Again, this is relied on as a squeeze with the prior art, in that it is alleged that the claims are not enabled insofar as they cover methods which do not use the method described in US 843.

v) That the same objections to validity apply to the conditional amendments proposed by Cubist.

The 047 Patent

8

Hospira alleges that the 047 Patent lacks inventive step over Lin & Jiang, Recovery and purification of the lipopeptide biosurfactant of Bacillus...

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