Patent Profile: Proteologics Announces Issuance of POSH siRNA Patent

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Patent Profile: Proteologics Announces Issuance of POSH siRNA Patent

January 9, 2008

Proteologics, Inc. announced today that it has been granted U.S. Patent No. 7,268,227. The ‘227 patent is the second U.S. patent to be awarded to the Rehovot, Israel-based biopharmaceutical company. According to the statement released by Proteologics, the ‘227 patent encompasses siRNA molecules that inhibit the expression of the antiviral drug target, hPOSH (human Plenty Of SH3 domains protein), a ubiquitin ligase that Proteologics identified as being essential for HIV biogenesis.

Proteologics’ research focuses primarily on the discovery of inhibitors for specific ubiquitin enzymes — E3 ligases — and their interacting proteins, and the therapeutic use of such inhibitors. Ubiquitin enzymes are known to play key roles in a variety of cell cycle and viral processes. Dr. Avram Hershko and Dr. Aaron Ciechanover, who lead Proteologics’ scientific advisory board, were awarded the 2004 Nobel Prize in chemistry, along with Dr. Irwin Rose, for their discovery of the ubiquitin system.

The ubiquitin system, in which proteins are covalently modified with ubiquitin (at left), is responsible for regulating most eukaryotic cellular processes, including transcriptional and cell cycle regulation, DNA repair, signal transduction, immune response, protein quality control, and metabolism. This system of regulation is carried out by three enzymes: E1, a ubiquitin-activating enzyme; E2, a ubiquitin-conjugating enzyme; and E3, a ubiquitin ligase that specifically recognizes proteins for ubiquitination and recruits E2 for the conjugation of ubiquitin. Human E3, rather than being a single protein, is actually a family of hundreds of distinct proteins, each of which targets a small set of proteins for ubiquitination. As a result of the essential physiological role of ubiquitination and the high degree of substrate specificity of the individual members of the E3 family, E3 ligases constitute attractive therapeutic targets.

Proteologics’ ‘227 patent issued from U.S. Application No. 11/031,737, filed January 7, 2005, which is a divisional of U.S. Application No. 10/293,965, filed November 12, 2002, which issued as U.S. Patent No. 7,250,250, and which claims the benefit of U.S. Provisional Application Nos. 60/345,846, filed November 9, 2001, and No. 60/364,530, filed March 15, 2002. Representative independent claim 1 of the ‘227 patent recites:

1. A composition comprising:
(a) a first nucleic acid which
(i) comprises between 5 and 100 nucleotides, of SEQ ID NO: 1 or a complement thereof, and
(ii) decreases the level of a POSH mRNA and/or a POSH polypeptide when introduced into a cell, and
(b) a pharmaceutically acceptable excipient.

Posted in Patent Profiles

8 responses to “Patent Profile: Proteologics Announces Issuance of POSH siRNA Patent”

kuppy kuppy the humble puppy

January 10, 2008

In what universe is claim 1 of the ‘227 patent a valid claim?
Let’s ignore the bogus functional limitation, per Rochester.
Is the PTO telling me that these guys invented all isolated nucleic acid molecules (with some salt, of course) comprising 5 (?!?!?!?) of the nucleotides in that sequence?
That seems to be the case.
Is Kevin Noonan keeping track? Kevin, this is another one for your list of crap patents.
How do you guys pick these winners anyway?

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Donald Zuhn

January 10, 2008

Humble Puppy:
Rochester may bear on whether the claimed invention has been adequately described, but the functional limitation would certainly not be ignored with respect to construing the claim.
As for the follow-up to Kevin’s November 20, 2007 article about patent quality, Kevin has been carefully analyzing the patents that were proposed in readers’ comments, and he assures me that he will soon be offering an article or two on the proposed patents.
Thanks for reading Patent Docs,
Don

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kuppy kuppy the humble puppy

January 10, 2008

“the functional limitation would certainly not be ignored with respect to construing the claim”
It’s nothing but a desired result from using the composition. Doesn’t matter if it’s in the preamble or the body.
How can it be fairly construed as a structural limitation of the composition?
The answer is that it can’t be. The claim is garbage. I shudder when I think of what must have gone down during prosecution.

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Kevin E. Noonan

January 10, 2008

Dear Kuppy:
I am keeping track, and I agree and disagree with your analysis.
Where I agree is that there is sufficiently little specificity in 5 nucleotides that I think the claim is overbroad in that respect. Generally, a sequence needs to be about 15 nucleotides long to be present randomly at a frequency of 1 in a million, so if the claim had said 15 to 100 nucleotides I think they would have been alright.
I disagree with the Rochester analysis. In Rochester, they had a claim to a method of doing something (specifically inhibiting COX-2) but no compound that would do so. Here, they have a composition claim to a specific (if overbroad) genus of oligonucleotides. And the method can be practiced using the overwhelming majority of that genus. There is no evidence that a 5-mer would not inhibit, and a method of inhibiting the level of POSH mRNA using oligos from 5 to 100 nucleotides of SEQ ID NO 1 is OK, since these inventors discovered that this sequence would work (I assume enablement and utility; the post and your comments are about overbreadth).
I looked at the PTO website and the Examiner’s reasons for allowance are that applicants discovered the POSH gene and its role in HIV particle maturation, and that HIV virus production could be reduced by inhibiting expression of POSH. According to applicants, their disclosure showed several antisense/RNAi fragments that were functional, and this overcame the asserted 112 rejections on written description/ enablement.
Although I think the art would inherently contain a 5-mer that reads on some portion of the POSH sequence, the claim further contains the limitation that the composition comprises a pharmaceutical excipient. So, looking at the effect of this claim, it will prevent a company from taking the fundamental discovery of POSH and its role in HIV virus production, and making an RNA-based drug. I’m not sure this is the wrong outcome.
Thanks for the comment.

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kuppy kuppy the humble puppy

January 10, 2008

“the claim further contains the limitation that the composition comprises a pharmaceutical excipient.”
i.e., some salt, found in everybody’s DNA solutions, regardless of whether they are intended to be pharmaceutically administered or not (again: intent not a relevant consideration for composition claims).
We agree that it’s overbroad and invalid and it doesn’t take a great deal of “analysis” to come to that conclusion. This facially ridiculous claim just “popped up”.
You also wrote: “According to applicants, their disclosure showed several antisense/RNAi fragments that were functional, and this overcame the asserted 112 rejections on written description/ enablement.”
Several fragments? I wonder how many of them consisted of just five sequential nucleotides from that SEQ ID.
The thing is: with that functional limitation in there, how can it not be enabled? Enablement is built in to the claim. If we read that functional limitation in, it doesn’t cover any otherwise undescribed or unconceived sequence that is NOT “enabled.” That’s the Rochester problem. That’s why such claims should not be allowed.
It would be nice if the PTO treated everybody so generously. Wonder what ProteoLogics did to get the nod.

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Kevin E. Noonan

January 10, 2008

Dear Kuppy:
There seem to be two ways of looking at this. The first is philosophical: these people should not have gotten a patent, based on your analysis. We can discuss this, and reasonable people can differ.
But the second is: what is the effect of the claim? If you are correct, then the claim is invalid and cannot be enforced. If construed the way you have construed it, then the claim “reads on” any 5-mer with a salt “found in everyone’s DNA solution” – in which case not only is the patent invalid, it is worthless.
But my point is that if the claim is construed to be valid, the only parties who are “injured” are those who would try to make a drug comprising 5 mucleotides from the sequence. Does it promote innovation for a third party to be able to do this? Isn’t that just like the days where academics published fundamental research, and drug companies profited from it with nothing back to the researchers? I think it best to think of what a claim protects, and whether the protection is commensurate with the disclosure, rather than arguing whether someone “deserved” to get the patent. After all, what you object to is the 5-mer limitation, and I think that’s too broad as well. But at the end of the day, if that scope is what enables this company to bring the drug to market, is it really so wrong that the researchers who made the discovery get to reap the benefits (for a limited time)?
Not perfect, but it never is.
Thanks for the comment.

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kuppy kuppy the humble puppy

January 11, 2008

“construed the way you have construed it, then the claim “reads on” any 5-mer with a salt “found in everyone’s DNA solution” – in which case not only is the patent invalid, it is worthless.”
That is the only reasonable way to construe the claim.
As for the philosophical issues, your points are well-considered but, frankly, beside the Main Point which is: claims issuing that are plainly invalid. It literally took me 1 minute to do the analysis. How can this stuff get through the PTO?
“at the end of the day, if that scope is what enables this company to bring the drug to market, is it really so wrong that the researchers who made the discovery get to reap the benefits (for a limited time)?”
Yes, it is wrong. As a matter of law, it’s wrong, that is, its incorrect. Not amoral, but incorrect. The PTO isn’t supposed to making moral decisions.
It’s entirely possible for a business to make an important discovery that is not patentable. It is not the job of the PTO to “fix” that in the business’s favor.
Lastly, I’ll note that a big source of the problem here is that these are composition claims and, as such, read on compounds utterly unrelated to the patentee’s alleged “discovery.” Relatively broad method claims drawn to treatments based on the “discovery” would be much less obnoxious, in my view, and (in my opinion) would fully satisfy the philosophical concerns you raised above.

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Kevin E. Noonan

January 11, 2008

Dear Humble:
I think we mostly agree, but one more comment. The question would be whether anyone ever made a 5-mer contained in a pharmaceutically-acceptable salt, wherein the 5-mer comprised a sequence found in SEQ ID NO 1. This is a question of fact, and the sequence certainly existed in the prior art in, for example, a random primner mixture. Note that the claim does not recite the term “isolated.” So clearly one interpretation is that we are done, and the claim is invalid.
But as I said before, the claims will need to be construed by a court, and there are certainly constructions that don’t immediately (or within 1 minute) lead to the conclusion that the claim is invalid. First is that a court could interpret the claim to require that the 5-mer be isolated, and in that case we come back to the question of fact (and facts can be tricky things). Establishing the existence of an isolated 5-mer would be required; if SEQ ID NO 1 contains a TTTTT that is easier than if it is a more complex sequence (and I think there would be evidence that would support the existence of any 5-mer you choose).
But I think the next question is the functional limitation. Valid claims can include functional limitations, which “read out” inoperative species (but not anticipating species unless they are themselves inoperative), and the issue then becomes whether it would be undue experimentation to determine whether a species is inoperative. In view of the large genus of fragments contained within the scope of the claim, that is unlikely.
What really happened was the examiner was not thinking about the 5-mers and the patentee wasn’t thinking about validity. As I said before, not perfect, but it rarely is, and as we agree, they are now stuck with a claim they will have a hard time enforcing.
Thanks for your comments.

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