Obviousness: could the skilled person make it without any inventive step?

16 December 2014

Birss J. rules on product by process claim construction, extension of scope, added matter and obviousness in Hospira v Genentech.

Birss J. has given a judgment which will thrill enthusiasts of esoteric questions of patent law in Hospira UK Limited v Genentech Inc. The detailed decision concerns two of Genentech's patents (EP 1 516 628 and EP 2 275 119) regarding the formulation of trastuzumab, the monoclonal antibody which is the active ingredient in Genentech's Herceptin medicine. The key points decided were on extension of scope, allowability of product by process claims, clarity, added matter and obviousness. The judgment can viewed in full here.

Genentech wished to make amendments to various of its claims, the primary claim considered being claim 1 of the '628 patent:

  1. A formulation comprising a lyophilized mixture of a lyoprotectant, a buffer, a surfactant and an antibody, wherein the molar ratio of lyoprotectant : antibody is 200 600 moles lyoprotectant : 1 mole antibody, wherein the lyoprotectant is trehalose or sucrose wherein the buffer is histidine, wherein the surfactant is polysorbate 20 and wherein the antibody is a monoclonal antibody huMAb4D5-8, obtainable by lyophilizing a solution containing 25 mg/ml huMAb4D5-8, 5mM histidine pH 6.0, 60 mM trehalose and 0.01% polysorbate 20.

Claim 2 was to a reconstituted solution, while the '119 patent had Swiss form claims to medicaments.

Extension of scope

An amendment to the specification of a patent will not be not allowed if it extends the protection conferred by the patent. Hospira contended that removing "wherein the molar ratio of lyoprotectant : antibody is 200 - 600 moles lyoprotectant : 1 mole antibody" from claim 1 would extend the scope of protection.

Birss J. applied the simple test of comparing the scope of the claims as granted with the scope of the claims as proposed to be amended. If the claim as proposed to be amended covered something that would not have been covered by the claims as granted, then the scope of protection would be extended by the proposed amendment and so it would not be allowed.

Hospira relied, by way of example, on a formulation obtainable, as described in proposed amended claim 1, using 25 mg/ml huMAb4D5-8, 5mM histidine pH 6.0, 60 mM trehalose and 0.01% polysorbate 20 but also including a second antibody (also at 25mg/mL).

Hospira asserted that this formulation would fall within the scope of the claim as proposed to be amended (since the presence of the extra antibody was permitted by the 'comprised' wording) but not as granted (because on Hospira's construction the ratio of lyoprotectant to antibody would be 180:1).

Genentech argued that the presence of a second antibody was irrelevant to the ratio in the granted claim, which should be construed as concerning only the ratio of trehalose:trastuzumab, and therefore the formulation would have fallen within the scope of the claims as granted.

Birss J. did not accept that, holding that it would be clear to the skilled reader that it was the ratio of the total amounts of antibodies and lyoprotectants which counted. The proposed amendments would therefore extend the scope of protection and so were not permitted.

Allowability of product by process claims

Is a product by process claim allowable? Claim 1 as proposed to be amended is for a product "obtainable by lyophilising a solution". Birss J. explained that European Patent Office practice is to permit 'obtainable by' only if there is no other way to describe a particular characteristic of the product in question.

One must know the characteristic in question and it must be true that in fact process conditions can be specified which do produce the characteristic. Birss J. gave as an example the claim in Johnson Mathey (T956/04), in which the only way to define the product by reference to the characteristic of crystallite size distribution was by reference to the process conditions which produced that particular characteristic.

Genentech contended that the characteristic which the process language defined was the molar ratio of the four ingredients in the lyophilised material. However, the court held that proposed claim 1 of '628 did not expressly state which characteristic was referred to and therefore the only realistic conclusion was that every conceivable characteristic was caught by the definition, including but not limited to molar ratio. As such, the proposed product by process wording could not be allowed.

Clarity

Hospira argued that claim 2 as proposed to be amended would lack clarity because the amounts of the components were insufficiently precise. The point was a short one and Birss J. rejected the allegation on the basis that the skilled man would see there was no inconsistency once rounding was taken into account.

Added matter

A patent may not be amended in such a way that it contains subject matter which extends beyond the content of the application as filed.

The court found that the point of the invention disclosed in the patent is to produce stable lyophilised protein suitable for parenteral administration to humans. The skilled reader would understand that a parameter which had an effect on stability was protein concentration. In addition, it was common general knowledge that lyoprotectants were used to protect the substance to be lyophilised from the stresses associated with freeze-drying.

The application referred to a wide range of molar ratios (lyoprotectant:protein) and the reader might well assume that stability might be possible at a wide range of ratios. However, this was not the same as teaching that molar ratio was independent of protein concentration.

The skilled reader would understand the specific disclosure of Table 5 as being that the ratio 360:1 (trehalose:trastuzumab) provided stability when the protein concentration was 25mg/ml. Genentech wished to generalise this specific disclosure into a general disclosure that a stable formulation could be produced by lyophilising any solution provided that the molar ratio of 360:1 of Table 5 was maintained. This general disclosure was new information not set out anywhere else in the application. Consequently the proposed amendment added matter.

Obviousness

Could he do it, would he do it? Yes he (the skilled person) could, but would he...? The distinction has long been a test of sorts for whether a step ("it") was an inventive one. Birss J. gave an alternative perspective on could/would in saying "it is more accurate to say that it is not patentable because the skilled person could make it without any inventive step". There is logic to this: if the skilled person could make something without invention, and the skilled person is an automaton that would do everything non-inventive in pursuit of the definite object in view, then the skilled person necessarily would do it. However, he reiterated the point that there is only a single statutory test (is it obvious?), that the issue is always multifactorial and based closely on the particular circumstances. Birss J. added by way of explanation that "If the outcome rides on the result of a single experiment, the fact the skilled person could carry it out does not usually mean the invention is obvious. One often needs to ask if they would carry out the test in the expectation of a positive result."

Both of these explanations (in quotes) are relevant to the finding of lack of inventive step over Carter (prior art teaching that trastuzumab, an anti-HER2 antibody, was in phase II clinical trials for breast cancer). The court found that "all of the differences between the claim and Carter are the result of nothing more than the application of routine screening techniques to common general knowledge excipients by a skilled team motivated in the way I have described already. There is no suggestion that any invention could be found to exist in the ratios or concentrations in the claim if the skilled team employed the relevant excipients." It is not relevant to ask whether the skilled person would use trehalose, it is sufficient that he could do so without taking any inventive step. The court elaborated that "It is not true to say that a real team would arrive at a formulation consisting of polysorbate 20, histidine and trehalose. It would be idle to pretend otherwise and Hospira do not do so. But what Hospira's submission is getting at is that the claimed result can be reached by the application of nothing other than routine approaches applied to excipients which were part of their common general knowledge."

That being so, the obviousness case hinged on Carter and what the skilled person would do with the information therein. It could be said that this question of what the skilled person would do with Carter is in fact the 'single experiment' on which the outcome of this case rides - a thought experiment, if you like. Would the skilled person, on the basis of the information in Carter, have carried out the project of attempting to create a lyophilised formulation of trastuzumab in the expectation of a positive result? Birss J found on the facts that knowledge that an anti-HER2 antibody was in phase II clinical trials for breast cancer would be of real interest to the skilled team. Together with the common general knowledge of earlier high-profile work on the HER2 receptor by the laboratory of Dennis Slamon and the clinician's interest in drugs being developed for that target, it would be a sufficient motivation for a skilled team to set about formulating trastuzumab with a desire to produce a working therapeutic formulation. It was entirely obvious for them to do so in the expectation of success.


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