Is Your Newly FDA-Approved Drug Eligible for Patent Term Extension?

We have recently spent some time determining whether a patent covering a drug which was newly approved New Drug Application (NDA) by the FDA, was eligible for patent term extension (“PTE”). The drug in question was the free base of the previously FDA approved salt.

Under 35 U.S.C. 156, the term of a patent that claims “a product, a method of using a product” shall be extended if….the product has been subject to a regulatory review period before its commercial marketing or use,” may be extended, provided that “the permission for the commercial marketing or use of the product after such regulatory review period is the first permitted commercial marketing or use of the product.” (Emphasis added) This is a powerful provision that can extend the exclusivity for an approved drug for an additional five years beyond the expiration of the patent, extending out to a maximum of fourteen years after NDA approval. Obviously, this represents the potential for significant extra revenue for the drug innovator company if the ability to exclude generic drug competitors for that additional length of time. A PTE application is a key part of an NDA approval for drug innovators. Our law firm has now filed several PTE applications for approved NDAs.

For our client, the key question was, is a free base of a previously approved salt a “first” use of the product, such that, the patent covering the free base was eligible for PTE?

The answer to this question revolves around the definition of the term “product”. The term “product” as used in § 156(a)(5)(A) is defined in § 156(f (1) to mean “drug product,” which is defined in § 156(f) (2) to mean the “active ingredient of (a) new drug, antibiotic drug, or human biological product . . . including any salt or ester of the active ingredient, as a single entity or in combination with another active ingredient.”

The USPTO, based on decisions such as Fisons v. Quigg, 8 U.S.P.Q.2d 1491 (D.D.C.1988), aff’d 876 F.2d 99 U.S.P.Q.2d 1869 (Fed.Cir.1989), and Pfizer Inc. v. Dr. Reddy’s Labs., 359 F.3d 1361 (Fed. Cir. 2004) to interpret “product” in 35 U.S.C. § 156(a)(5)(A) has embraced an expansive definition of the term “drug product.” The USPTO interprets “drug product” to mean “active moiety.” According to this interpretation, the active moiety would be the drug product, regardless of whether the active moiety is formulated as a salt, ester, or other non-covalent derivative. This is an expansive definition of “drug product”, with the result that newly FDA-approved derivatives of an active moiety such as esters and salts of a previously FDA-approved drug would not be considered a new drug product. Thus, newly FDA-approved derivative type drugs would not be eligible for patent term extension. Under this interpretation, we would have to advise the client that likely, the newly approved free base form of the previously approved salt would not be eligible for patent term extension.

However, there is another vein of cases with a narrower definition of “drug product.” In the Federal Circuit’s 1990 decision in Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392, 13 USPQ2d 1628 (Fed. Cir. 1990), construed the term “product” in 35 U.S.C. § 156(a)(5)(A) to mean “active ingredient.” In this interpretation, an “active ingredient” is the active ingredient physically found in the drug product, which would include any salt, ester, or other non-covalent derivative of the active ingredient physically found in the drug product. Thus, this is a narrower definition of “drug product”, such that the approved drug is defined as including both the active moiety and whatever salt, ester or non-covalent derivative it also comprises. For some time, there was a question about which interpretation of “drug product” controlled here: the broader “active moiety” interpretation (one favored by the USPTO), or the narrower “active ingredient” interpretation seen in the 1990 Federal Circuit decision.

Two more recent cases, decided in May 2010, show that the narrower, “active ingredient” interpretation of the statute is the proper interpretation of “drug product.” See, e.g., Photocure ASA v. Kappos, 603 F.3d 1372, (Fed. Cir. 2010). In Photocure, the USPTO denied the requested PTE but the Federal Circuit overturned that decision and granted PTE eligibility. MAL hydrochloride was the applied-for drug and ALA hydrochloride was the previously approved drug. MAL is the methyl ester of ALA. Therefore, what was approved was the salt, and what was applied for was the methyl ester of the same underlying compound. The PTO stated that since the “underlying molecule” of MAL is ALA, MAL is simply formulated differently, and denied PTE. The district court balanced the factors to determine whether allowing PTE met with the intent of the statute: the court considered the separate chemical composition, the separate patentability, and the separate FDA approval of MAL, and held that the statutory requirements for PTE were met. The CAFC affirmed this reasoning, and held that where the product is substantively changed in a way that produces a new and separately patentable product having improved properties and requiring full FDA approval, the product is new under 35 U.S.C. 156 and is thus eligible for PTE. In other words, MAL is the active ingredient for a new and improved drug product and is thus eligible for PTE.

So what of our newly approved free base of the previously approved salt? Is it eligible for PTE under this new case law? It appears that there is a good chance that it should be eligible for PTE in accordance with Photocure. Our analysis shows that the free base was in fact a separately patentable form of the drug moiety. The free base form was granted a patent over the art which teaches the salt. Further, the free base required a new approval (NDA) before the FDA. Thus, the facts appear to point to a reasonably good chance for a determination of PTE eligibility for the patent covering our newly FDA-approved free base.

However, there have been several PTE decisions from the USPTO since Photocure, indicating that the USPTO is continuing to interpret “drug product” to mean the narrower definition of “active moiety.” For example, in October 2011, the USPTO rejected the 2010 application for PTE for BUTRANS™, which contains as its active ingredient, the compound buprenorphine (free base), in view of the fact that there were previously approved drugs contained as their active ingredient a salt of buprenorphine, buprenorphine HCl. However, BUTRANS™ had a separate NDA and was separately patentable over buprenorphine HCl . No final decision appears to have been rendered in this case as yet.

Therefore, it is our opinion that in our client’s case, that while we do believe that the Federal Circuit’s 2010 decisions indicate that their free base patent is eligible for PTE, we had to advise that the likeliest outcome is that the USPTO will reject the PTE application, just as it did for buprenorphine (free base). It is likely that if the USPTO rejects our client’s PTE application, that just as Photocure plaintiffs did, our client’s recourse to obtain their PTE is resort to filing a lawsuit to cause the USPTO to grant their PTE.