By Andrew Williams —

Last month, in Photocure
ASA v. Kappos, the Federal Circuit affirmed the decision by the U.S. District Court for the Eastern District of Virginia that methyl
aminolevulinate hydrochloride ("MAL hydrochloride"), brand name
Metvixia®, is entitled to patent term extension pursuant to 35 U.S.C. §
156.  Metvixia® was approved by the
FDA for use in photochemistry or photodynamic therapy to treat actinic
keratoses — precancerous cell growths on the skin.  MAL hydrochloride is the methyl ester of aminolevulinic acid
hydrochloride ("ALA hydrochloride").  However, MAL hydrochloride received patent protection (U.S.
Patent No. 6,034,267 ("the '267 patent")), in part because the
patentees demonstrated its improved therapeutic properties as compared to ALA
hydrochloride.  In addition, even
though the FDA had previously approved ALA hydrochloride for the same use, MAL
hydrochloride was considered a "new drug," and therefore required
full FDA approval.

After receiving FDA approval of MAL hydrochloride,
Photocure applied for patent term extension of the '267 patent pursuant to 35
U.S.C. § 156(a).  In pertinent
part, the statue reads:

35 U.S.C. §156(a) The term of a patent which claims a product, a method
of using a product, or a method of manufacturing a product shall be extended in
accordance with this section . . . , if–

* * * *

    (a)(4) the product has been subject to a regulatory
review period before its commercial marketing or use;
    (a)(5)(A) except as provided in subparagraph (B) or
(C) [not here relevant], 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 under the provision of law under
which such regulatory review period occurred . . .  .

The FDA pointed out that the MAL hydrochloride is
an ester of ALA hydrochloride, and proposed that 35 U.S.C. § 156(a)(5)(A) was
not met.  The PTO, in turn, denied
the requested term extension on the basis that the two molecules are the same
product, because the underlying molecule (ALA) is the same.  Therefore, according to the Patent
Office, the molecule was simply formulated differently in the two drugs.  And, because the "product"
had previously been approved by the FDA, the '267 patent, claiming MAL
hydrochloride, was not entitled to patent term extension.

35 U.S.C. § 156 further defines "product"
as:

§156(f) For purposes of this section:
    (1) The term "product" means:
        (A) A drug product.

* * * *

    (2) The term "drug product" means the
active ingredient of—
        (A) a new
drug, antibiotic drug, or human biological product (as those terms are used
in the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act),
. . . including
any salt or ester of the active ingredient, as a single entity
or in combination with another active ingredient.

(emphasis added).  Therefore, to understand what "products" are
eligible for patent term extension, it is useful to look at 35 U.S.C. §
156(a)(5)(A) with the definition substituted for the term "product":

35 U.S.C. §156(a)(5)(A): except as
provided in subparagraph (B) or (C) [not here relevant], the permission for the
commercial marketing or use of the [new
drug, including any salt or ester of the active ingredient,] after
such regulatory review period is the first permitted commercial marketing or
use of the [new drug, including
any salt or ester of the active ingredient,] under the provision of
law under which such regulatory review period occurred . . . .

The Patent Office interpreted "active ingredient"
to mean "active moiety" — in this case, the same underlying molecule
ALA.  Therefore, because MAL
hydrochloride is an ester of an active ingredient/moiety that had already been
approved, it was not entitled to the patent term extension provisions of § 156.

The Federal Circuit rejected this interpretation,
stating that the statute is unambiguous.  The Federal Circuit found that the active ingredient was MAL, and
because ALA hydrochloride is not a salt or ester of MAL hydrochloride, the '267
patent coving MAL hydrochloride was entitled to term extension.  In truth, however, MAL hydrochloride is
the ester of ALA hydrochloride.  Nevertheless, this decision was not entirely surprising, because in
1990, the Federal Circuit had an almost identical case in Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392 (Fed. Cir. 1990).

Interestingly, even though the Federal Circuit
relied entirely on statutory interpretation, the Court appeared persuaded by
the fact that MAL hydrochloride was both separately patentable and required
separate regulatory approval.  Of
course, in these cases, the second approved drug is always going to be
separately patentable — otherwise there will be no patent whose term would need
to be extended.  So, how important
was the fact that separate regulatory approval was required.  It is perhaps telling to analyze this
case from the hypothetical situation where the ester was instead the first
approved product.  For example, using
the present case, if MAL hydrochloride had first obtained FDA approval, could
Photocure have obtained patent term extension for claims to ALA hydrochloride upon
FDA approval?  Applying the
calculus of the Photocure case, the
second active ingredient would be ALA.  MAL hydrochloride is an ester of ALA hydrochloride.  Therefore, substituting these terms
into 35 U.S.C § 156 (in pertinent part):

The term of a patent . . . shall be extended . . .
if . . . the permission for the commercial marketing or use of ALA
hydrochloride, including MAL hydrochloride (the ester of ALA hydrochloride) . .
. is the first permitted commercial marketing or use of ALA hydrochloride,
including MAL hydrochloride (the ester of ALA hydrochloride) . . .  .

And because, according to this hypothetical, MAL
hydrochloride had already been approved by the FDA, no patent covering ALA
hydrochloride would be entitled to patent term extension.  In other words, in the present case, the
'267 patent was entitled to term extension because ALA hydrochloride is not an
ester of MAL hydrochloride, but, in reverse situation, MAL hydrochloride is an
ester of ALA hydrochloride, and therefore the patent would not be entitled to
term extension.  It would logically
appear from this decision that no one should be able to obtain term extension
for a patent covering a drug product if the ester of that drug product had been
approved first.  And, this should
be true even if separate regulatory review was required for the second product.

Of course, it is not entirely clear that this makes
sense.  Nor is it clear that the
Federal Circuit would actually arrive at such a conclusion because it is
unclear if they would ignore the fact that such a drug underwent separate
regulatory approval.  One possible
out would be if the active ingredient in the hypothetical was determined to be
ALA, not ALA hydrochloride.  Thus,
MAL hydrochloride would be the ester and the salt of the active ingredient.  The statute clearly reads "ester or salt," so the patent would be
eligible for term extension.  Still, it will be interesting to see what happens if, and/or when, such
a situation occurs.

Photocure ASA v. Kappos (Fed. Cir. 2010)
Panel: Circuit Judges Newman, Rader, and Linn
Opinion by Circuit Judge Newman