From October 2016 to March 2017 the team is joined by Guest Kats Rosie Burbidge and Eibhlin Vardy, and by InternKats Verónica Rodríguez Arguijo, Tian Lu and Hayleigh Bosher.

Wednesday, 26 June 2013

Alzheimer's Disease Antibody Patent Insufficient - Lilly v JAI

What is a poor moggy to do?  On the same day, no less, the IPKat learns of the consultation on the 15th draft of the Rules of Procedure of the UPC, and of Mr Justice Arnold’s exciting decision in Eli Lilly & Company v Janssen Alzheimer Immunotherapy (let’s call them Lilly and JAI).  What is this Kat going to use to lull him off on his Katnap?  132 pages of, well, Rules, or 90 pages (and 354 paragraphs, since you ask) of dense law and lovely science relating to Alzheimer’s disease and its treatment.  (Do cats get Alzheimer’s, asks Merpel?  The IPKat can’t quite remember…)

A pretty picture
Well, happily, now the IPKat has had a chance to peruse, read (and mark and inwardly digest, if not quite yet learn) both documents, and so now, dear readers, he is happy to tell you about the Lilly v JAI case.  The citation is EliLilly & Company v Janssen Alzheimer Immunotherapy [2013] EWHC 1737 (Pat) (25 June 2013) and you can read it in full on the ever-faithful BAILII, complete with pretty pictures.  Pictures do so help with the science, don’t you find?

As you will have gathered by now, the case was about Alzeimer’s Disease (AD), and, in particular, its treatment using an antibody to β- amyloid peptide (also referred to as amyloid-β or Aβ). The first nearly 100 paragraphs of the judgment is technical background which explains all about this, but, briefly, AD is, as Arnold J faithfully records, associated with:
Parenchymal deposits of amyloid called neuritic plaques, which are dense extracellular deposits found in the brain’s grey matter. The principal component of such plaques is Aβ. The Aβ deposits are surrounded by degenerating neurites which are in turn covered in astrocytes and microglia.
Accordingly, an antibody to Aβ might serve to reduce these deposits and ameliorate the symptoms of AD.

Claim 1 of the patent was:

A pharmaceutical composition comprising an antibody to Aβ and a pharmaceutically acceptable non-toxic carrier or diluent, for use in preventing or treating a disease characterised by amyloid deposit in a patient, wherein the isotype of the antibody is human IgG1.

Arnold J dismissed an allegation of added matter, and that claim 1 of the Patent lacks novelty over International Patent Application No. WO96/25435 (“Konig”) which was published on 22 August 1996.  JAI contended that claim 1 is novel over Konig since (i) Konig does not disclose an antibody to Aβ of the human IgG1 isotype and (ii) Konig does not disclose use of (a pharmaceutical composition comprising) the antibody in preventing or treating a disease characterised by amyloid deposit.  Arnold J accepted both of these contentions.

A less pretty but informative picture
On inventive step, Arnold J considered “The key question, therefore, is what expectation of success the skilled team would have had if they contemplated implementing Konig’s proposal.”

The IPKat was delighted to see that feline metaphors are still going strong in UK Patent litigation:

Lilly contends that, if these points would have been perceived by the skilled team to be “lions in the path”, there is nothing in the Patent to show that they were in fact “paper tigers”. I disagree. For reasons that I will explain when dealing with insufficiency, I consider that the specification of the Patent does contain enough to make it plausible that (pharmaceutical compositions comprising) some antibodies to Aβ will be effective to prevent and/or treat AD…

In the light of this Arnold J concluded:

Overall, I conclude that Konig did not make it obvious to make an antibody to Aβ “for use in preventing or treating a disease characterised by amyloid deposit”.

In relation to Lilly’s contention that claim 1 was obvious over European Patent Application No. 0 613 007 A2 (“Becker”) published on 31 August 1994, Arnold J noted:

I shall deal with this very briefly, since in my opinion it is manifest that claim 1 cannot be obvious over Becker if it is not obvious over Konig.

Arnold J also rejected an Agrevo-type obviousness objection.

So far therefore all going well for JAI.  But wait, we are only at page 64.  Sufficiency is yet to come.

An interesting preliminary point in relation to insufficiency is that whereas in Generics (UK) Ltd v Yeda Research and Development Co Ltd [2012] EWHC 1848 (Pat) Arnold J put restrictions on the degree to which post-published evidence may be relied on in relation to inventive step (in particular the issue of whether the patent renders it plausible that the invention works), he rejected a submission by JAI that there should be any such limitation in relation to demonstrating insufficiency of the patent.  He decided that the approach to adopt should be as follows:

For the reasons set out above, the court must undertake a two-stage enquiry. The first stage is to determine whether the disclosure of the Patent, read in the light of the common general knowledge of the skilled team, makes it plausible that the invention will work across the scope of the claim. If the disclosure does make it plausible, the second stage is to consider whether the later evidence establishes that in fact the invention cannot be performed across the scope of the claim without undue burden.

On the evidence, Arnold J found as follows in relation to the disclosure of the patent:

Thus I conclude that the disclosure in the Patent does make it plausible that passive immunisation of a suitable antibody to Aβ will be effective to prevent and/or treat a disease characterised by amyloid deposit.

(Still going well for JAI, notes Merpel, but we are still only at page 74, growls the IPKat, because Arnold J ominously continues…)

That is not the end of the enquiry, however. It remains to be considered whether the Patent makes it plausible that any antibody to Aβ (provided it is of IgG1 isotype) will be effective to prevent and/or treat a disease characterised by amyloid deposit.

And on the evidence he decided:

Accordingly, I conclude that the disclosure of the Patent does not make it plausible that any antibody to Aβ (provided it is of IgG1 isotype) will be effective to prevent and/or treat a disease characterised by amyloid deposit. It only makes it plausible that N-terminal antibodies will be effective. It follows that the Patent is insufficient.

He went on for good measure to decide (in case he was wrong on the “plausible” point above) whether the patent was additionally invalid for insufficiency either because the invention could not be performed without undue burden, or because of excessive breadth of the claims.  Finding the patent bad in both respects, the Judge stated:

The upshot is that the Patent does no more than invite the skilled team to perform what Prof Wisniewski rightly described as a “very significant research project with a high prospect of failure” and, if they succeed, claims the fruits of their research. It is therefore insufficient: see Novartis AG v Johnson & Johnson Medical Ltd [2010] EWCA Civ 1039, [2011] ECC 10 at [77].

Finally, Arnold J held that the Lilly product solanezumab did infringe the patent (or would if it were valid).

The IPKat was wondering following recent cases of Lilly v HGS and Regeneron whether broad antibody claims were inherently immune to insufficiency attack and is reassured to discover that this is not necessarily so.  How do his dear readers see this case?  There is certainly more to be mined from this meaty judgment.

Merpel meantime has been scampering around the corridors of the EPO, and heard that the patent in suit (EP 1 994 937) was revoked by the Opposition Division at Oral Proceedings on 10 June 2013 on the grounds of sufficiency (Main Request) and added matter (Auxiliary Requests).  Will the EPO Boards of Appeal or the UK Court of Appeal get the final decision in first?


Anonymous said...

It is commendable that Mr Justice Arnold has upheld a biotech patent for inventive step. However his approach on sufficiency was very strict. Essentially the difficulty of development work to select an effective antibody was very influential in his decision. No right minded biotech patent attorney would have advised the patentee to delay filing until that development work was completed, and so the logic is unsympathetic to pharma/biotech applicants who are torn between getting an early filing date and getting more data. Whilst development difficulties are relevant to sufficiency Courts need to be very careful to keep these in perspective.

Also I am not sure that I would entirely agree with a novelty analysis that seems to rely on a lack of data in the prior art about whether therapy was demonstrated versus an analysis of whether the antibodies would be likely to have the inherent property of being therapeutic. Sufficiency and support are different concepts, and must be dealt with very carefully if part of a novelty analysis.

Finally Mr Justice Arnold discusses plausibility in relation to sufficiency. I am sure the outcome was not affected, but plausibility relates to inventive step (whether the problem was solved) and unless it is dealt with as part of inventive step UK case law on it is going to get confused.

Anonymous said...

I have to disagree with the previous anon who is displaying the standard 'life's not fair for biotech' attitude that has existed as long as biotech attorneys themselves. If you believe the patentee filed too early in this case then that was their choice. That is the risk of competitive research. Maybe, just maybe, if their work was so far away from what had gone before, then no-one else would have stumbled across it while they dotted all i's and crossed all t's.

MaxDrei said...

The standard American put-down of "First to File" is that it forces inventors to file prematurely, when all they have is speculation. I counter with the warning, that in a First to File jurisdiction, the worst thing you can do is file before the case is ready for patenting (because you end up donating the roadmap to the others but with no rights of your own). In fact, it is First to Invent that fails to promote the filing of patent applications as soon as there is available, for the first time, an enabling disclosure of the claimed subject matter.

At the EPO, DG3 (Frau Dr Kinkeldey and others) has done a lot of good work in biotech, to set the "ready for patenting" bar at a level that balances fair protection for inventors with reasonable legal certainty for the others.

Upthread, a commentator complains about misappropriation for Art 83 of the Art 56 "plausible" test. For me, the fewer the number of concepts, the better. Thus, we use the same concept of "disclosure" for all of Art 54, 87 and 123(2) and the EPC caselaw is much the better for that simplicity.

Anonymous said...

In response to MaxDrei plausibility is needed in pharma/biotech as a distinct separate test to evaluate whether the data (and the spec as whole) shows the problem has been solved. That is important in an area where data is difficult and expensive to obtain, and so this test helps to keep a fair balance between applicants and third parties. The test has come about because of a practical need. I believe Mr Justice Arnold applied the test in this case in an incorrect way, at least in comparison to the way the EPO uses it where it is very much part of the inventive step analysis.

MaxDrei said...

Does the stuff "work"? Does it work over the full scope of the claim? What technical effect does the stuff deliver? Does the claimed subject matter truly solve the objective technical problem? Is the claim enabled over its full scope? To answer any of these questions, do you not first have to ask yourself whether the data that are adduced in support of patentability, Art 56, Art 83, are "plausible"?

In fact, how can you decide fairly, without first asking yourself that pre-question? Anon, you are suggesting you are biotech. I am not. But are you telling us that, in biotech, DG3 does not so ask itself?

Anonymous said...

How is it in Biotech then, that patents are routinely granted - and yet years of painstaking proof still must follow 'to make sure' you have what you actually claim?

Shouldn't the grant of the patent itself not be done before the proof is there? Does not an improvidently granted patent (trial runs fail) retard the progress by prematurely placing a Do not Trespass sign in the art field?

Subscribe to the IPKat's posts by email here

Just pop your email address into the box and click 'Subscribe':