Millennium Pharma v. Sandoz (Federal Circuit 2017)
As part of a brand-generic pharma battle, the district court invalidated a set of Millennium’s patent claims covering its Velcade drug used to treat multiple myeloma.[1] The district court held that the claims (covering the chemical compound active ingredient) were obvious as the inherent result of an obvious process.
In particular, the claims cover a freeze dried (“lyophilized”) version of the compound “D-mannitol N-(2- pyrazine) carbonyl-L-phenylalanine-L-leucine boronate.” The active portion of the compound is the boronate (bortezomib), which was known to work but was unstable. Researchers tried and failed to create liquid formations and so turned to freeze-drying. To achieve that end, mannitol was added to the compound in a way formed a chemical bond with the boronate – leading to dramatic improvement in stability. When a patient ingests the new drug (a “prodrug”), the body breaks-down the compound and allows the active ingredient to work.
The boronate portion was known in the prior art for its medical use and the mannitol portion was a known bulking agent. The process of freeze-drying was also known. However:
No reference taught or suggested reacting bortezomib with mannitol, and no reference hinted that … an esterification reaction might occur during lyophilization. No reference taught or suggested that the product of such lyophilization would be a new chemical compound that would solve the problems that had inhibited development of bortezomib in oncology.
In its decision, the district court recognized that the resulting compound was likely unexpected, but focused on the process of getting to that result – holding that the claimed compound was simply the “natural result” inherent to the lyophilized process and that it would have been obvious to try the process on boronate + mannitol. On appeal, the Federal Circuit has reversed.
The easy part of the decision for the district court focused-in on the motivation to combine boronate and mannitol. The district court found that an Adams Patent “pointed directly to mannitol” for the combination. However, according to the Federal Circuit, “the Adams Patent’s fail[s] to mention mannitol.”
In my view, this easy-part is sufficient for the patentee to win, and my preference would be for the court to delete the rest of its muddled opinion – and instead rest its case on the lack of the motivation to combine. The remainder of the decision is somewhat difficult to follow because it jumps back and forth dancing around but never answering the basic question: If the combination would have been obvious to try, would its natural result also be considered obvious? At times, the court appears to agree that obviousness would follow, while other sections of the opinion suggest the compound would not have been obvious since its actual structure was so unexpected.
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A patent claim is obvious when, “if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.”[2] Here the appellate panel focused the question to: “whether a person of ordinary skill, seeking to remedy the known instability and insolubility and to produce an efficacious formulation of bortezomib, would obviously produce the D-mannitol ester of bortezomib, a previously unknown compound.”
On the topic of inherency in particular, the court seems to have simply strung together several loosely related sentences. Take the following pair as an example:
Sandoz argues that although lyophilization in the presence of mannitol produced an unexpected result, the result was “inevitable” and thus “inherent,” and thus not “inventive.” However, invention is not a matter of what the inventor intended when the experiment was performed; obviousness is measured objectively in light of the prior art, as viewed by a person of ordinary skill in the field of the invention . . .
In the end, the reversal makes sense, but the law created is somewhat of a mess.
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[1] Millennium Pharm., Inc. v. Sandoz Inc., No. 12-1011, 2015 WL 4966438 (D. Del. Aug. 20, 2015); U.S. Patent No. 6,713,446.
[2] 35 U.S.C. 103.
You know, the reality is that games are being played here between EE patents and chem patents.
The fact is that there are a limited number of processes and other compounds that can be tried. The fact is too that many labs simply exhaustively try them all and exhaustively make new compounds and they try them on zebra fish.
Do not all such compounds, whether by Flash of Genius or by brute force, only work anyway by natural laws?
Too many labs?
“The fact is that there are a limited number of processes and other compounds that can be tried.”
I’d like to see a proof of that.
Though you’re right that there may seem to be some game playing between chem and EE (or moreso compooter) patents.
All of the PTAB “trials” I’ve seen from EE are nigh a farce. Though I haven’t seen many. And I’m reading about the whole balloons kerfuffle over at IPwatchdog and that’s really got me a bit annoyed.
“and that’s really got me a bit annoyed.”
at whom?
Idk, the judges, Lee, her replacement, congress? Whomever? Although I do think that they maybe could have made some decent backup claims that didn’t involve functional limitations for the first patent. And I didn’t really get into the 2nd and 3rd patent’s obviousness analysis, though just from what I see I’m really kind of doubting their 103 is all that gr8.
The 112 issue in the first patent is an oddball, and it’s a shame that they didn’t write the decision very well, because now the patent owner thinks that the board was taking issue with “substantially filled with water” or some similar phrase, supposedly in the vein of POSITA not understand the scope of that phrase. When in reality it appears the board’s issue was with how that phrase modified the overall phrase that it was a part of. And I could understand their issue, but idk, it seems to pass the Nautilus test to me, I don’t know if they should use Nautilus, but I think Nautilus is probably the right standard, it is more or less universal and more than generous.
And the worst part about the whole thing is I mean it’s such a cut and dry case of copying and all. It’s pretty clear he made this wholly new combo that got everyone all aflutter and sold a gazillion units, the exact kind of thing the patent system most should be there to protect, and he’s paying millions to work this out? Ridiculous.
I also think that were possible, the PTAB should be required to consult with the original examiner to get their input, obviously they issued the thing, they probably know “what the office’s thinking was” better than anyone.
Thanks 6.
So, has David Hricik taken money from Google? Has Dennis taken money from Google?
Let’s face it. We are in a post-ethics, post-integrity era, anyone that has power and/or money should be assumed to be corrupt.
So, far these questions have gone unanswered. We should assume unless they are answered that both professors are on the Google doll.
I’m pretty sure no one wants to see the professors “on the Google Doll”.
I would be very interested in how much Google has offered Dennis. My bet is that Google has offered Dennis at least $1 million dollars and Dennis probably has a much higher probability of becoming a full professor the more anti-patent he is. This is probably due to Prof. Lemley’s vast political power throughout academia.
I’d guess buying Lemley is worth $10 million.
Has Google offered to pay for blog posts to be written by Dennis?
The writing of blog posts pails in comparison to the “editorial” shaping of the narrative of any replies to blog posts.
Just my view.
Google offered me 100 milly.
…NOT to write…
😉
From the IPO News report on this decision:
“The Federal Circuit said the district court erred in its obviousness analysis. The prior art contained no teaching or suggestion of the D-mannitol ester of bortezomib, that it would form through lyophilization, or that it would have “long-sought properties of stability and solubility, and sufficiently dissociate to release bortezomib … all critical to effective use for treating multiple myeloma.”
PM The prior art contained no teaching or suggestion of the D-mannitol ester of bortezomib, that it would form through lyophilization,
And just taking those facts at face value, the only question is whether one or more of those details are recited in the claim. If they are recited, then in all likelihood the claim should be non-obvious. Yes, it’s a lucky break for the patentee that it tried mannitol with this compound and it reacted to form a shelf-stable pro-drug that doesn’t dissociate as a lyophilate but does dissociate when administered. That’s just how the cookie crumbles (or, more accurately for this case, how the cookie doesn’t crumble).
In other good news, the previous formulation — which still has utility and value — is now in the public domain and, at least according to Econ 101, the price should have dropped.
I think that inherency of unexpected result should be applied only to anticipation but not to obviousness analysis.
In the case of obviousness, the inherency is only imaginary.
Also, if inherency of unexpected result is applied to obviousness analysis, the imaginary unexpected result will be always there.
It should be noted that unexpected result is for rebuttal against prima facie case of obviousness.
If unexpected result is denied by the inherency, what is the use of unexpected result?
In the case of anticipation, even if the result is unexpected, it is already there (not imaginary) in the prior art.
Therefore, the denial of patentablity is justified.
It should be noted that unexpected result is for rebuttal against prima facie case of obviousness.
Right. The result is inherent to the suggested combination. The unexpected nature of the result is part of the rebuttal to the prima facie case.
Note,however, that it’s not just the fact that some result is “unexpected” that saves the day. The claim needs to be narrowly written so that its scope doesn’t venture beyond the structural/procedural details that lead to the unexpected result. And a result that is merely “unexpected” is not going to work when the suggestion in the art is strong and the result in question is trivial (e.g., “lyophilized pharmaceautical comprising X and Y has been unexpectedly found to be distasteful to rabbits, thereby decreasing the likelihood that your pet rabbit will consume a misplaced pill and become sick.”). Finally, an unexpected result in your application as filed is (or certainly should be) worth more than one cooked up fifteen years later in litigation or during prosecution of a continuation application.
The active portion of the compound is the boronate (bortezomib), which was known to work but was unstable. Researchers tried and failed to create liquid formations and so turned to freeze-drying. To achieve that end, mannitol was added
Just so there’s no confusion about the technology here, THIS much is completely obvious. Freeze-drying with mannitol and “lyophilized compositions comprising mannitol and drug X” are prima facie obvious regardless of what X is (maybe a few exceptions on the margins) and that’s been the case for quite a while.
One of the other bits of weirdness in this case is the part where the CAFC tries to make hay out of the failure of each reference to teach the invention. That’s not how it works, guys. Maybe check your own case law re “attacking the references individually.”
I think what is going wrong here is that the USPTO does not have the equivalent of a ‘defining the problem’ step which the EPO uses. Something can be obvious to simply treat myeloma, but it might not obvious that you would get no side effects, for example. Motivation must analyse motivation to do what exactly, looking at what was actually achieved. This is important in pharma inventions because different problems are being simultaneously solved, and each problem requires its own motivation and expectation of succeeding analysis.
John, indeed!
At the EPO, the “Problem and Solution Approach” indeed invokes something called the “objective technical problem”. For me, perhaps the chief merit of the EPO-PSA is that it imposes a strict structure on the debate about obviousness. At the EPO, everybody knows that structure and argues within it. Boy does that help, to streamline the debate and keep it focussed.
Of course, if there were any systemic defect in the PSA structure, which somehow skews the balance between attacker and defender, we would have heard about it by now.
Instead, there is just bleating from those who suppose that they understand EPO-PSA but do not.
Your feelings are noted.
As well as your own bleetings, given as even your vaunted “objective” test has subjective elements still – as has been demonstrated in the past (by others).
But nice of you to denigrate any who would question your view, and to do so without a modicum of evidence.
As is your views merely survive as far as the “veracity” of your feelings and more serve merely as the typical “here, wear my glasses, they work for me” pablum.
Others? Demonstrated? News to me. I mean what I wrote, that nobody who understands EPO-PSA has yet demolished the capability of the EPO-PSA structure to do justice between the adversarial parties.
Others? Demonstrated? I invite you to remove your own one way mirror finish, one eye monocle and give us citations please. If not for my benefit then for any other reader to this blog who might take a passing professional interest in debating rival approaches to obviousness.
If I remember right, last time around, NWPA had something to say. Perhaps NWPA is your “others”? But that was before the AIA, I think. Perhaps he would like to kick in again here
Nice to see that you recognized my note to “by others.”
Sadly, since the argument was not mine, I do not recall the particulars (hence I have no citations to offer). Also, I did not bookmark those conversations (and I do not remember if it was Night Writer, but tend to doubt it, as that is not his usual focus). I am thinking that it was perhaps AAA JJ.
Inherency…
😉
(can anyone say “Big Box of Protons, Neutrons and Electrons”…?)
…or how about “House/Morse”…?
Are not all future improvements to a computing machine “already in there”…?
I haven’t read this case but the title of the post doesn’t help clear anything up.
“When is an [sic] the inherent, but unexpected result obvious?” is the wrong question.
The right question is: “When does the inherent result of a suggested combination render the claim non-obvious”
The correct answer is “When the inherent result is unexpected, but unexpected results alone will not suffice to render a suggested combination non-obvious if the suggestion was potent and the unexpected result is not.”
However, invention is not a matter of what the inventor intended when the experiment was performed; obviousness is measured objectively in light of the prior art, as viewed by a person of ordinary skill in the field of the invention . . .
Oy. Someone was in a big hurry.
MM, I am not so sure that discoveries are invalidated, or should be invalidated, simply because the inventor stumbled upon the result by trying brute force combinations.
Did not Congress explicitly address the fact that the matter with which discoveries may be made is not pertinent to 103?
Ned: I am not so sure that discoveries are invalidated, or should be invalidated, simply because the inventor stumbled upon the result by trying brute force combinations.
I think the answer is “it depends.” I didn’t say anything about how (or whether) the manner in which the invention was made would affect the result. But it certainly can and will affect the result, no matter what the CAFC says.
MM said “suggested” combination, presumably meaning the combination was suggested by prior art? That is not the same as your “brute force combinations,” by which I assume you mean large numbers of un-suggested experiments [like Edison’s thousands of experiments to find a longer-lasting carbonized-filament lightbulb.]
But even if a combination is suggested by the prior art, and would inherently [but un-described and un-appreciated] produce a claimed compound if conducted, is there not still a possible “teaching away” argument if the combination reference also indicates that it as inoperative, ineffective, dangerous, or the like?
is there not still a possible “teaching away” argument if the combination reference also indicates that it as inoperative, ineffective, dangerous, or the like
Definitely a possibility but pretty unlikely in the field of pharma formulations where the general parameters and ranges of stabilization/bulking/delivery agents have been suggested and re-suggested over and over again. Sure, there’s some people out there who are allergic to mannitol. Yes, there may be some cheaper alternatives to try. But that’s not “teaching away” from using mannitol in a lyophilization prep/composition.
Was there an expert to fill in the blanks created by the references? Seems like perhaps the district court created new law where really a proper expert declaration would have sufficed.
Indeed, unless effectively rebutted in live cross-examination and/or by a more effective expert declaration from the other side.
The district court also found that the prior art taught toward making esters to improve stability of bortezomib. In view of this finding, I’m not sure if the reversal makes sense. What apparently got these claims over the hump is that an ester derivative was made by an unexpected reaction with mannitol.
The district court also found that the prior art taught toward making esters to improve stability of bortezomib. In view of this finding, I’m not sure if the reversal makes sense. What apparently got these claims over the hump is that an ester derivative was made by an unexpected reaction with mannitol.
Thanks D
Hey guys obscure IDS question here. If the office is checking an IDS’s citations off and one of the patent documents is “withdrawn” (I’m not even sure why that would happen but I guess reexam or something), is it proper for the office to mark it “considered” or, should it be struck through on the IDS?
6 it is very common at the EPO to “withdraw” a published pending patent application. That withdrawal doesn’t magic away the published status of the application.
Perhaps the citation you are looking at, the “patent document” is an A publication of the EPO or some other non-US Patent Office?
Nah this one is US. I guess I could look for it on tha google or epo website.
I should be clear perhaps that when I say it shows as “withdrawn” literally all there is in East is a page that says it was withdrawn. There is no publication of the reference there anymore. The rest is just blank.
“That withdrawal doesn’t magic away the published status of the application.”
Yes, but could it mean that something else was “magic’ed” away?
Like veracity?
Like the difference between science fiction and actual prior art?
Lots of science fiction is “published” all the time, and yet (at least in the US) we have a current “elephant in the room” flaw in that novelty and obviousness will treat veracity differently when it comes to treating a prior art source on its own (novelty) or merely in some combination (obviousness).
Is it supposed to be an issued patent? I think what you are talking about is if an applicant files a petition to withdraw from issue shortly before the Tuesday the patent will issue, then the patent will show as “withdrawn” on the USPTO site. Reexamined patents will look normal but will have a certificate appended to it. If there is no publication of the document then I don’t think you can acknowledge a reference you haven’t seen.
It definitely sounds like it was withdrawn from issue, although this doesn’t have to be at the applicant’s request. The USPTO is also able to withdraw a patent from issue before it is published in the Official Gazette.
This can happen before the actual issuance but after the patent number is assigned. The applicant gets a notification of the forthcoming patent number before it actually issues, so they could potentially list it on an IDS before issuance, leading to this situation.
6, I think you would probably have to strike through the reference on the IDS. If there is a PGPub for the reference, you could cite it on the 892 and explain what happened. But if it is unpublished, you would need to just strike through it and not explain why until the reference actually does get issued.
Thanks for the opinion Plurality, but as it turns out google had a copy so I ended up just looking at that one.
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