CORRECTION: I did not actually go read the underlying 1928 studies -- I just assumed what they were asserting -- but a closer look reveals that the older studies did NOT claim that Nicotinamide Riboside was in milk; only that the milk had an anti-pellegragenic effect. NR's structure was not even known at the time. You'd think I might have picked that up from the subheading on Page 28 of the '807 response: "Goldberger and Tanner Does Not Disclose Isolated Nicotinamide Riboside."
Goldberger said in 1924 that milk cures pellagra (Exhibit 1006). Tramell said in 2016 that the milk that cures pellagra contains NR, a major pre-cursor of NAD+ (Exhibit 1007). You can read below that Goldberger had not a clue what was in the milk: "...some as yet unrecognized dietary complex," which maybe does not impact the proper construction of the term "isolated," but sheds light on the strength of the prior art.
Elysium's request to the Patent Trial and Appeal Board (PTAB) to invalidate two ChromaDex* patents (8,197,807 and 8,383,086) via Inter Partes Review (IPR) attempts to show that the two patents are invalid because they were anticipated by prior art -- in other words, these were not new inventions, but previously disclosed methods. Here are the documents:
Elysium's challenges to both patents rely heavily on studies done by Joseph Goldberger in the 1920's in which the presence and effect of Nicotinamide Riboside in milk was examined.
Elysium's Argument Against the '807 Patent
Elysium's argument against the '807 patent is that NR was already known to naturally occur in cow's milk as revealed in a 1928 journal article, and NR was isolated in buttermilk, so the patent claim for an isolated form of NR was previously disclosed.
Quick Snide Response: If Dartmouth had patented buttermilk, then, yeah, I guess so. But Dartmouth did not patent buttermilk, and Elysium isn't selling buttermilk, so why are we talking about this?
Dartmouth's Response on the '807 Patent
First, Petitioner has not provided any evidence that either of its prior art references of the proposed Grounds discloses the essential claim element of “isolated nicotinamide riboside” as claimed in independent claim 1 of the ’807 patent. Petitioner instead relies on an improper claim construction and expert testimony for the inapposite conclusion that nicotinamide riboside present in milk or buttermilk is “isolated” when milk is removed from a cow. Because neither prior art reference of the proposed Grounds discloses isolated nicotinamide riboside like that claimed in the ’807 patent, Petitioner cannot establish that the references anticipate the claims of the ’807 patent.
Yeah, that's what I meant to say. Isolated means isolated; if it's in buttermilk, it's not isolated.
Second, Petitioner has not provided any evidence that either of its prior art references of the proposed Grounds discloses the essential claim element of a pharmaceutical composition comprising nicotinamide riboside formulated “in 2 admixture with a carrier” as claimed in independent claim 1 of the ’086 patent. Because neither asserted prior art reference discloses nicotinamide riboside formulated in admixture with a pharmaceutically acceptable carrier as disclosed in the ’086 patent, Petitioner cannot establish that the references anticipate claim 1 of the ’086 patent.
In other words, the 1928 article does not disclose a pharmaceutically acceptable carrier as part of an admixture.
Third, Petitioner has not provided any evidence that either of its prior art references of the proposed Grounds discloses compositions comprising nicotinamide riboside that “is isolated from a natural or synthetic source,” as required by claim 2 of the ’086 patent. Petitioner instead relies on an improper claim construction and questionable expert testimony for its argument that nicotinamide riboside present in milk or buttermilk is “isolated” from a natural source when milk is removed from a cow. Petitioner cannot establish that the references anticipate claim 2 of the ’086 patent.
Steptoe here is arguing that removing milk from a cow is not the same as isolating it from a natural source: "Petitioner’s cow argument fails because removing milk from a cow is not the same as fractionating the nicotinamide riboside contained in that milk from the other cellular components."
Fourth, Petitioner has not provided any evidence that either of its prior art references of the proposed Grounds discloses a pharmaceutical composition comprising nicotinamide riboside that “increases NAD+ biosynthesis upon oral administration,” as required by dependent claim 5 of the ’086 patent. Petitioner instead relies on an argument regarding milk that was already considered by the Examiner and overcome during prosecution of the parent application to the ’086 3 patent. Petitioner cannot establish that the references anticipate claim 5 of the ’086 patent.
In other words, the Patent Examiner KNEW that NR was present in milk, and only granted the patent based on the additional consideration of bioavailability based on oral administration, which was not previously disclosed.
I would think that settles the matter.
Let's look at the '086 Patent:
Elysium's argument against the '086 Patent
"The ’086 patent purports to disclose the discovery of a biosynthetic pathway that is naturally present in eukaryotic cells and converts nicotinamide riboside to NAD+...Based on the discovery of this natural phenomenon, the ’086 patent claims pharmaceutical compositions comprising nicotinamide riboside."
Relying on the same 1920's studies, Elysium concludes that the skim milk disclosed by Goldberg was a pharmaceutical composition comprising nicotinamide riboside in admixture with a carrier, wherein said composition is formulated for oral administration -- milk! I think the argument here is that because the skim milk fed to the dogs in the 1928 study had the desired effect, there is nothing left to patent -- NR was administered.
Dartmouth's Response on the '086 Patent
First, Petitioner has not provided any evidence that either of its prior art references of the proposed Grounds discloses a pharmaceutical composition as recited in claim 1 and in each of the dependent claims of the ’086 patent. Because neither prior art reference of the proposed Grounds discloses a pharmaceutical composition as described and claimed in the ’086 patent, Petitioner cannot establish that the references anticipate claim 1 of the ’086 patent.
In other words, the thing patented was a pharmaceutical composition; skim milk is not a pharmaceutical composition.
Second, Petitioner has not provided any evidence that either of its prior art references of the proposed Grounds discloses the essential claim element of a pharmaceutical composition comprising nicotinamide riboside formulated “in admixture with a carrier” as claimed in independent claim 1 of the ’086 patent. Because neither asserted prior art reference discloses nicotinamide riboside formulated in admixture with a pharmaceutically acceptable carrier as disclosed in the ’086 patent, Petitioner cannot establish that the references anticipate claim 1 of the ’086 patent.
In other words, skim milk is not a pharmaceutically acceptable carrier. For example, it is not necessarily compatible with other ingredients, non-injurious (some people are allergic to milk!), and perhaps binding or stabilizing the compound.
Third, Petitioner has not provided any evidence that either of its prior art references of the proposed Grounds discloses compositions comprising nicotinamide riboside that “is isolated from a natural or synthetic source,” as required by claim 2 of the ’086 patent. Petitioner instead relies on an improper claim construction and questionable expert testimony for its argument that nicotinamide riboside present in milk or buttermilk is “isolated” from a natural source when milk is removed from a cow. Petitioner cannot establish that the references anticipate claim 2 of the ’086 patent.
In other words, the PTAB ought to construe "isolated from a natural or synthetic source" as meaning "fractionated from other cellular components," not as isolating a natural source," because the patent specifically describes methods of isolation that involve fractionation and centrifuges, not milking a cow.
Fourth, Petitioner has not provided any evidence that either of its prior art references of the proposed Grounds discloses a pharmaceutical composition comprising nicotinamide riboside that “increases NAD+ biosynthesis upon oral administration,” as required by dependent claim 5 of the ’086 patent. Petitioner instead relies on an argument regarding milk that was already considered by the Examiner and overcome during prosecution of the parent application to the ’086 patent.
As Dartmouth apparently argued during the original patent prosecution proceedings, "The mere fact that nicotinamide riboside is present in milk is in no way suggestive or predictive of an oral formulation of nicotinamide riboside being bioavailable and increasing biosynthesis of NAD+ upon oral administration.”
Conclusion
Intuitively, I would assume that the mere presence of NR in skim milk or buttermilk would not prevent someone from later patenting a method of making this stuff into a vitamin supplement or a pharmaceutical if they prepared it the right way.
Now, having seen the legal arguments describing the difference between what was known in 1928 and what was patented, the additional components strike me as clear, significant, and consistent with the way Patent Law is supposed to work.
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* If these are ChromaDex Patents, why is Dartmouth involved? Dr. Charles Brenner is the inventor; Dartmouth owns the patents; and ChromaDex licensed the patents from Dartmouth.