Orange Book Vol. 42/Supp. 6 News: Watch out for the breadth of your use codes
This posting is late since I am talking about Vol. 42, Supp. 6 of the Orange Book. The data for Supp. 6 was released by the FDA in mid-July. However, I updated my Orange Book Companion immediately when the data was released, so my subscribers received the new data on time. Similarly, if you are not a subscriber but enjoy checking out my free Orange Book Companion “What’s New” each month, that was also ready to view in mid-July.
So, what is late? It’s this Supp. 6 news where I discuss a mass delisting of patents for a single product in which all of the patents had what appears to be overly broad use codes. Please read on.
Supp. 6 added 52 new patents to the FDA’s Orange Book. However, unlike Supp. 5, there were a number of patents that were delisted or were newly tagged as being the subject of a delisting request. Two of four patents listed for Serenity Pharmaceuticals’ NOCTIVA (desmopressin acetate) were delisted. Both strengths of NOCTIVA are shown in the Orange Book as having been discontinued. So not likely to be a major event.
The big delisting event in Supp. 6 belongs to Takeda’s GATTEX KIT (teduglutide recombinant). There were twenty patents listed in the Orange Book for GATTEX KIT in Supp. 5, and now there are only three. Of those three remaining patents, two are the subject of new delisting requests in Supp. 6! So, but for the formalities of the delisting process to protect the 180-day exclusivity of one or more so-called “first filers,” there would be but one patent remaining listed for GATTEX KIT, 7,056,886 (“the ‘886 patent”) following this mass delisting.
A subplot for the ‘886 patent is that it had been the subject of an Inter Partes Review, and a number of its claims were canceled. Those canceled claims included all of the method-of-use claims (69-75) that were in the patent. The Federal Circuit affirmed the IPR decision on November 15, 2017, and the USPTO issued an IPR Certificate on June 19, 2019 showing that claims 61-75, among others, had been canceled. So, starting at least upon the issuance of the IPR Certificate, the ‘886 had no method-of-use claims.
I then confirmed that the ‘886 patent had a Use Code (U-1320: “Treatment of adult patients with short bowel syndrome who are dependent on parenteral support”) listed in the Orange Book. The patent, itself, may still be eligible for listing in the Orange Book since not all of its claims were cancelled in the IPR. But a patent should only have a use code if it contains claims to an approved method of using the drug, which the ‘886 patent no longer does.
Dovetailing with my observation of a Use Code now being listed for a patent that has no method-of-use claims, a bipartisan mix of US senators sent a letterto USPTO director Kathi Vidal in June expressing concern over so-called “patent thickets.” The senators were particularly concerned about overuse of continuation filings to create patent thickets as a potential means of delaying generic entry. But why are the senators concerned about thickets? One point was made in a July 21, 2022 "FDA Law Blog" posting discussing patent thickets and continuations where author Sara Koblitz said “while the term of the patent is not extended, multiple patents increase litigation burden.” In other words, while patent thickets cannot extend exclusivity for a drug, they might result in a longer period of litigation during which the ANDA filer might be unable (due to the 30-month stay) or be reluctant to launch due to the threat of treble damages for willful infringement.
So what did the patent listings for GATTEX KIT look like before the delistings and delisting requests? There was the ‘886 patent from Family ID 10867197 described above, and nineteen additional patents all from Family ID 36319726 (“the ‘726 family”). The Orange Book-listed members of the ‘726 family were the parent 7,847,061, two divisionals (9,060,992 and 9,545,434) and sixteen continuations. Those who equate multiple continuations with a patent thicket may believe that they have found one.
Then I noticed another interesting thing about the GATTEX KIT Orange Book listings. The claims of all of the listed patents (other than the ‘886 patent) were directed solely to methods of use, and those patents all had the same use code description (numbered either as U-1320 or U-2308: don’t ask me how that happened!):
Treatment of adult patients with short bowel syndrome who are dependent on parenteral support.
For simplicity, I shall refer to the use code description as the “use code,” as the FDA did in the Federal Register notice for the Medicare Modernization Act Final Rule (see 81 Fed. Reg. 69580 (October 6, 2016) at 69580, column 3).
It turns out that the above use code is a verbatim recitation of the original 2012 approved indication for GATTEX KIT. So was Takeda (or one of its predecessors) saying via the same use code that all nineteen patents claim the same thing? Wouldn’t that have created a §101 statutory double patenting issue?
Well, it turns out that the nineteen listed members of the ‘726 family do not all claim the same thing. All of them claim subject matter that is narrower than the original approved indication recited in the U-1320/2308 use code recited above. That, of course, creates a different problem. Instead of having the same use code, each listed patent in the ‘726 family should have a different use code since they all claim somewhat different subject matter!
FDA regulations require that use codes should not be broader than the broadest claim in a patent that is being listed as a method of use patent. As discussed by the FDA in their response to comments concerning the agency’s regulations to implement the Medicare Modernization Act (“MMA):
Although we decline to provide hypothetical examples, the following general principles illustrate the clarifying revisions to the regulations regarding the content of use codes.
* * *
Patented method of use is narrower than an indication or other approved condition of use: If the method of use claimed by the patent does not cover an indication or other approved condition of use in its entirety, then the NDA holder must describe only the specific approved method of use claimed by the patent—not the broader indication or other approved condition of use that may include, but is broader than, the use claimed by the patent.
81 Fed. Reg. 69580 (October 6, 2016) at 69598-99 (italics in the original; underlining for emphasis).
It turns out that the claims of a number of the listed patents from the ‘726 family are directed to treating specific issues experienced by short bowel syndrome patients, and so are easily seen as being narrower than the very broad U-1320/U-2308 use code of treating “adult patients with short bowel syndrome who are dependent on parenteral support.” Here are a couple of examples:
9,539,310: “a method of decreasing fecal wet weight of a patient having short bowel syndrome . . .”
9,555,079: “a method of reducing or suppressing gastric secretion of a patient having short bowel syndrome . . .”
9,572,867: “a method of reducing recurrence of kidney stones in a patient having short bowel syndrome . . .”
So, shouldn’t each of the above patents have a use code limited to the breadth of the broadest claim instead of the very broad U-1320/2308 “treatment of adult patients with short bowel syndrome who are dependent on parenteral support”? Here are a few rough hypotheticals:
9,539,310 Use Code XXXX: “A method of decreasing fecal wet weight of a patient having short bowel syndrome who is dependent on parenteral support . . . by administering teduglutide recombinant . . .”
9,555,079 Use Code XXXY: “A method of reducing or suppressing gastric secretion of a patient having short bowel syndrome who is dependent on parenteral support by administering teduglutide recombinant . . .”
9,572,867 Use Code XXXZ: “A method of reducing recurrence of kidney stones in a patient having short bowel syndrome who is dependent on parenteral support . . . by administering teduglutide recombinant . . .”
All italics are for emphasis.
But there is another issue that I found in the claims of every member of the ‘716 family that could affect the use code that should be listed for the patent. It has to do with the patient population to which all the claims are limited.
Every independent claim of the listed members of ‘726 family requires that the patient be one who presents with “colon in continuity with remnant small intestine.” According to an article from Medscape General Medicine (MedGenMed. 2004; 6(2) 12) by Dr. Alan L. Buchman, Short Bowel Syndrome patients with colon in continuity with remnant small intestine are but a subpopulaton of Short Bowel Syndrome patients. The article states that patients with Short Bowel Syndrome:
can be divided into 2 distinct subgroups: those with colon in continuity with their small intestine and those without colon.
So while I am not a gastroenterologist, it would appear that the use code for every one of the nineteen listed members of the ‘726 family should include the “colon in continuity with small intestine” element of the claims in order to accurately delineate the breadth of the patent’s claims. Here are a few more rough hypotheticals to show how a more appropriate use code would look for the above-recited three patents:
9,539,310 Use Code XXXX: “A method of decreasing fecal wet weight of a patient having short bowel syndrome presenting with colon in continuity with remnant small intestine. . . by administering teduglutide recombinant”
9,555,079 Use Code XXXY: “A method of reducing or suppressing gastric secretion of a patient having short bowel syndrome presenting with colon in continuity with remnant small intestine. . . by administering teduglutide recombinant”
9,572,867 Use Code XXXZ: “A method of reducing recurrence of kidney stones in a patient having short bowel syndrome presenting with colon in continuity with remnant small intestine. . . by administering teduglutide recombinant”
All italics are for emphasis.
And if you think that the vast majority of patients might be those who have the colon in continuity with remnant small intestine, so that it is not an important claim limitation, think again. The Clinical Study section 14.1 of the GATTEX KIT label (Study 1) states that “the colon was not in continuity in 44% (37/85) patients.” (italics for emphasis). Study 1 shows that a large percentage of Short Bowel Syndrome patients did not have “colon in continuity with small intestine.” So for use code purposes, the “colon in continuity” element of the claims in all of the listed patents of the ‘726 family appears to be a very significant patient population limitation.
Of course, some readers might think of use codes that are much better than my hypotheticals, above. I am merely trying to remind you that some thought must be given to use codes, and that the FDA requires use codes to not be broader than the broadest claim found in a listed method-of-use patent.
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