Another two bite the dust – Hospira v Genentech

The IPKat has just been perusing the meaty yet compact decision in the case of Hospira v Genentech (Hospira UK Ltd v Genentech Inc [2014] EWHC 1094 (Pat) (10 April 2014)) which came out last Thursday from Mr Justice Birss.  It concerns two patents, related only in that they both concern the antibody trastuzumab, more famously known as Herceptin (RTM), which is used for the treatment of breast cancer.  Other than that they are quite different, the first EP 1 210 115 being concerned with a dosage regime, and the second EP 1 308 455 with a purified composition.

EP 1 210 115
Claim 1 was as follows:

Use of the anti-ErbB2 antibody huMab4D5-8 [trastuzumab]
in the manufacture of a medicament for use in a method for treating a human patient diagnosed with a breast cancer characterized by overexpression of ErbB2, 
said method comprising the steps of 
administering intravenously to the patient an initial dose of 8mg/kg of the anti-ErbB2 antibody; and 
administering intravenously to the patient a plurality of subsequent doses of the antibody in an amount that is 6 mg/kg, wherein the doses are separated in time from each other by three weeks.

This claimed treatment regime involves an 8mg/kg loading dose and subsequent doses of 6mg/kg on a three weekly schedule. This regimen can be summarised as 8 + 6 q3w [don't you just love those pharmacist abbreviations, says Merpel - apparently the "q" stands for "quaque", meaning "every"].

Was this not the skilled team you were looking for?

This was held to be obvious over the prior FDA-approved treatment regime of 4 + 2 q1w.  The clinician, it was held, would consult with the pharmacokinetics expert and decide to go ahead with a trial of a three-weekly dosing schedule and select the claimed doses.

In the alternative, if the claim was not obvious, then the judge would have considered the patent invalid for insufficiency, because “the skilled team would not conduct a clinical trial of the claimed three weekly dosing regimen based on the information in the patent read in the light of the common general knowledge”.

EP 1 308 455
Claim 1 was as follows:

A composition for therapeutic use comprising a mixture of anti-HER2 antibody and one or more acidic variants thereof,
wherein the amount of the acidic variant(s) is less than about 25%,
and wherein the acidic variant(s) are predominantly deamidated variants wherein one or more asparagine residues of the anti-HER2 antibody have been deamidated,
and wherein the anti-HER2 antibody is huMAb4D5-8 [trastuzumab],
and wherein the deamidated variants have Asn30 in CDR1 of either or both VL regions of humMAb405-8 converted to aspartate,
and a pharmaceutically acceptable carrier.

This patent was about purifying trastuzumab so that it contained mainly only one acidic variant, namely one in which the asparagine residue at the 30 position had been deaminated (hydrolysed) to aspartate, and that in an amount of less than “about 25%”, which was agreed to mean less than 24.5%.  It is noteworthy that the claim was not limited to any particular method, but claimed the product as such.

This was held to lack novelty over a prior Genentech PCT application PCT/US96/12251 ("Andya") which was published as WO 97/04801.  In particular a specific formulation disclosed therein, which the judge found to be enabling, in which 82% of the protein was native trastuzumab, so that the maximum level of acidic variants was 18%, was held to anticipate the claim.

The claim was also held to lack inventive step having regard to “Waterside” - prior art consisting of slides presented at a conference by Reed Harris from the Analytical Chemistry Department of Genentech.  Other inventive step attacks were rejected.

Finally, for good measure, a declaration of non-infringement was granted to Hospira in relation to this patent, since the levels of acidic variants were outside the range.

The judgment records that “Both patents were opposed in the EPO. In both cases the Opposition Division has held the patent is invalid. Both are presently under appeal before the Technical Board of Appeal.”  The upshot of the case is that, subject to any appeal in the UK, Hospira has cleared the way to sell generic trastuzumab after the supplementary protection certificate (SPC/GB04/015) based on the basic underlying patent held by Genentech on trastuzumab (EP 0 590 058) expires on 28th July 2014.