  United States Court of Appeals
      for the Federal Circuit
                 ______________________

     RAPID LITIGATION MANAGEMENT LTD.,
      FORMERLY CELSIS HOLDINGS, INC.,
                IN VITRO, INC.,
               Plaintiffs-Appellants

                            v.

      CELLZDIRECT, INC., A DELAWARE
     CORPORATION AND WHOLLY-OWNED
   SUBSIDIARY, INVITROGEN CORPORATION,
        A DELAWARE CORPORATION,
             Defendants-Appellees
            ______________________

                       2015-1570
                 ______________________

   Appeal from the United States District Court for the
Northern District of Illinois in No. 1:10-cv-04053, Senior
Judge Milton I. Shadur.
                 ______________________

                  Decided: July 5, 2016
                 ______________________

    ANDREW JOHN PINCUS, Mayer Brown LLP, Washing-
ton, DC, argued for plaintiffs-appellants. Also represented
by PAUL WHITFIELD HUGHES; ADAM GLENN KELLY, JOHN
A. COTIGUALA, Loeb & Loeb LLP, Chicago, IL; LAURA ANN
WYTSMA, Los Angeles, CA.
2          RAPID LITIGATION MANAGEMENT   v. CELLZDIRECT, INC.



    DAVID G. MANGUM, Parsons Behle & Latimer, Salt
Lake City, UT, argued for defendants-appellees. Also
represented by C. KEVIN SPEIRS.

   LYNN PASAHOW, Fenwick & West, LLP, Mountain
View, CA, for amicus curiae National Venture Capital
Association. Also represented by CAROLYN CHANG,
MICHAEL JEFFREY SHUSTER.

    ALICE O. MARTIN, Barnes & Thornburg LLP, Chicago,
IL, for amicus curiae Biotechnology Industry Organiza-
tion. Also represented by BRADLEY JOHN OLSON, Washing-
ton, DC; HANSJORG SAUER, Biotechnology Industry
Organization, Washington, DC.
                  ______________________

    Before PROST, Chief Judge, MOORE and STOLL, Circuit
                          Judges.
PROST, Chief Judge.
    Appellants seek review of the district court’s sum-
mary judgment determination that U.S. Patent
No. 7,604,929 (“’929 patent”) is invalid under 35 U.S.C.
§ 101. The district court concluded that the ’929 patent is
directed to a patent-ineligible law of nature—that hepato-
cytes are capable of surviving multiple freeze-thaw cy-
cles—and that the patented process lacks the requisite
inventive concept. Celsis In Vitro, Inc. v. CellzDirect, Inc.,
83 F. Supp. 3d 774 (N.D. Ill. 2015), supplemented, 94 F.
Supp. 3d 940 (N.D. Ill.). Because the ’929 patent claims
are not directed to a patent-ineligible concept, we vacate
and remand.
                              I
    Hepatocytes are a type of liver cell that have a num-
ber of attributes useful for testing, diagnostic, and treat-
ment purposes. For example, hepatocytes can be used to
investigate how drugs under development may be metabo-
RAPID LITIGATION MANAGEMENT    v. CELLZDIRECT, INC.        3



lized by the liver or can be used to measure a drug’s
toxicity or other effects on liver biology. Certain factors,
however, limit their use: fresh hepatocytes can only be
obtained from liver resections or non-transplantable livers
of organ donors, and their lifespan is short. ’929 patent
col. 2 ll. 25-35. Supply is thus erratic, making availability
limited and unpredictable. Id. at col. 2 ll. 22-35.
    Prior to the invention of the ’929 patent, scientists de-
veloped “cryopreservation” techniques to preserve hepato-
cytes for later use. Id. at col. 2 ll. 36-40. These methods
generally comprised freezing hepatocytes at frigid tem-
peratures; then, when needed, thawing them and recover-
ing the viable cells using density gradient fractionation.
Id. at col. 2 l. 36-col. 3 l. 4, col. 10 ll. 30-60.
     The prior art cryopreservation method had its prob-
lems, however. It was understood that the process could
damage the hepatocytes, leading to poor recovery num-
bers of viable cells. Id. at col. 3 ll. 5-32. Furthermore,
these prior methods were unsuitable for preparing multi-
donor hepatocyte pools. Id. at col. 3 ll. 33-60. Because
hepatocytes from different donors generally have different
metabolic properties, researchers desired to pool hepato-
cytes from various source livers to create a hepatocyte
preparation approximating average liver cells. Id. at col.
11 ll. 5-27. Such pools are useful research tools to study a
drug’s impact on a representative population. But be-
cause of the limited availability of donor livers and
hepatocytes’ short lifespan, pooled samples from multiple
donors could only be created by first accumulating and
freezing enough hepatocytes from single donors, then
thawing and combining them for immediate use. Id. at
col. 3 ll. 49-60. Given the understanding that cryopreser-
vation could damage cells, prevailing wisdom was that
hepatocytes could be frozen only once and then had to be
either used or discarded. Celsis, 83 F. Supp. 3d at 777-78.
This severely limited the creation of pooled hepatocyte
products. Id.
4          RAPID LITIGATION MANAGEMENT       v. CELLZDIRECT, INC.



    The inventors of the ’929 patent discovered that some
fraction of hepatocytes are capable of surviving multiple
freeze-thaw cycles. As inventor Dr. Hardy testified,
“initially we just proved that you could twice freeze the
cells and still have viable cells. . . . [T]he unexpected
outcome was that cells twice frozen behaved like cells that
were once frozen.” Id. at 778-79 (quoting J.A. 148-49).
    Armed with this discovery, the inventors developed an
improved process of preserving hepatocytes, claimed in
the ’929 patent. In general, the improved process com-
prises: (A) subjecting previously frozen and thawed cells
to density gradient fractionation to separate viable cells
from non-viable ones; (B) recovering the viable cells; and
(C) refreezing the viable cells. ’929 patent col. 19 l. 56-col.
20 l. 20. The claims specify that the resulting hepatocyte
preparation can be thawed and used immediately, exhibit-
ing 70% viability after the second thaw. Id.
     The ’929 patented process has a number of ad-
vantages over the prior art. By separating out and re-
freezing only the viable cells, the preserved hepatocyte
preparations can be thawed and used later without unac-
ceptable loss of viability. Id. at col. 3 ll. 64-67. Pooled
hepatocyte preparations are also much more easily made:
hepatocyte samples from single donors can be pooled
together to create a composite preparation that can be re-
frozen for later use. Id. at col. 3 l. 67-col. 4 l. 6, col. 11 l. 2-
col. 12 l. 27. This was not possible with the prior art
cryopreservation techniques.          Appellant employs the
improved process in its LiverPoolTM product, which com-
prises multi-cryopreserved, pooled hepatocyte prepara-
tions useful for a wide variety of research purposes.
    Claim 1 is representative of the ’929 patent. It re-
cites:
    1. A method of producing a desired preparation of
      multi-cryopreserved hepatocytes, said hepato-
      cytes being capable of being frozen and thawed
RAPID LITIGATION MANAGEMENT   v. CELLZDIRECT, INC.        5



       at least two times, and in which greater than
       70% of the hepatocytes of said preparation are
       viable after the final thaw, said method com-
       prising:
         (A) subjecting hepatocytes that have been fro-
         zen and thawed to density gradient fractiona-
         tion to separate viable hepatocytes from non-
         viable hepatocytes,
         (B) recovering the separated viable hepato-
         cytes, and
         (C) cryopreserving the recovered viable
         hepatocytes to thereby form said desired
         preparation of hepatocytes without requiring
         a density gradient step after thawing the
         hepatocytes for the second time, wherein the
         hepatocytes are not plated between the first
         and second cryopreservations, and wherein
         greater than 70% of the hepatocytes of said
         preparation are viable after the final thaw.
    Additional dependent claims are directed to the type
of density gradient fractionation, the type of hepatocytes,
viability, and pooling. For example, with respect to
pooling, claim 5 recites:
    5. The method of claim 1, wherein said prepara-
       tion comprises a pooled preparation of hepato-
       cytes of multiple sources.
    IVT sued LTC for infringing the ’929 patent. 1 In
response, LTC filed a motion for summary judgment of



   1    The original suit was brought by Celsis In Vitro,
Inc. against CellzDirect, Inc. and Invitrogen Corporation.
After various corporate transactions, the named parties
are now Plaintiffs-Appellants, Rapid Litigation Manage-
ment Ltd. and In Vitro, Inc. (collectively, “IVT”), and
6        RAPID LITIGATION MANAGEMENT   v. CELLZDIRECT, INC.



invalidity under 35 U.S.C. §§ 101 and 112. The district
court granted the motion, finding the ’929 patent invalid
under § 101 and dismissing the action with prejudice
(without reaching the § 112 issues). Celsis, 83 F. Supp. 3d
at 785-86. In finding the patent invalid under § 101, the
court applied the Supreme Court’s two-step framework for
determining patent eligibility. See Alice Corp. v. CLS
Bank Int’l, 134 S. Ct. 2347, 2355 (2014) (citing Mayo
Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct.
1289, 1294, 1296-98 (2012)). At step one, the court con-
cluded that the ’929 patent “is directed to an ineligible
law of nature: the discovery that hepatocytes are capable
of surviving multiple freeze-thaw cycles.” Celsis, 83 F.
Supp. 3d at 783. At step two, the court determined that
“the patented process lacks the requisite inventive con-
cept,” observing that, upon discovering the cells’ capabil-
ity of surviving multiple freeze-thaw cycles, the inventors
simply “reapplied a well-understood freezing process.” Id.
at 783-84.
    IVT appeals the court’s decision. We have jurisdiction
under 28 U.S.C. § 1295(a)(1). We review the court’s grant
of summary judgment under the law of the regional
circuit; here, the Seventh Circuit’s de novo standard.
Memorylink Corp. v. Motorola Sols., Inc., 773 F.3d 1266,
1270 (Fed. Cir. 2014) (citing Chaklos v. Stevens, 560 F.3d
705, 710 (7th Cir. 2009)). The issue of patent-eligibility
under § 101 is a question of law that we review without
deference. CyberSource Corp. v. Retail Decisions, Inc.,
654 F.3d 1366, 1369 (Fed. Cir. 2011).
                            II
    Section 101 permits the patenting of “any new and



Defendants-Appellees, Cellzdirect, Inc. and Invitrogen
Corporation (which merged with another corporation to
form Life Technologies Corporation) (collectively, “LTC”).
RAPID LITIGATION MANAGEMENT   v. CELLZDIRECT, INC.        7



useful process, machine, manufacture, or composition of
matter, or any new and useful improvement thereof,”
subject to other requirements of the title. 35 U.S.C. § 101.
The Supreme Court has “interpreted § 101 and its prede-
cessors . . . for more than 150 years” to “contain[] an
important implicit exception: Laws of nature, natural
phenomena, and abstract ideas are not patentable.” Alice,
134 S. Ct. at 2354 (quoting Ass’n for Molecular Pathology
v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2116 (2013)).
The concern underlying these judicial exclusions is that
“patent law not inhibit further discovery by improperly
tying up the future use of these building blocks of human
ingenuity.” Id. (internal quotation marks omitted) (quot-
ing Mayo, 132 S. Ct. at 1301).
    The Supreme Court has recently articulated a two-
part test for distinguishing patents that claim one of the
patent-ineligible exceptions from those that claim patent-
eligible applications of those concepts. Id. (citing Mayo,
132 S. Ct. at 1294, 1296-97). Step one asks whether the
claim is “directed to one of [the] patent-ineligible con-
cepts.” Id. If the answer is no, the inquiry is over: the
claim falls within the ambit of § 101. If the answer is yes,
the inquiry moves to step two, which asks whether, con-
sidered both individually and as an ordered combination,
“the additional elements ‘transform the nature of the
claim’ into a patent-eligible application.” Id. (quoting
Mayo, 132 S. Ct. at 1297). Step two is described “as a
search for an ‘inventive concept.’” Id. (quoting Mayo, 132
S. Ct. at 1294). At step two, more is required than “well-
understood, routine, conventional activity already en-
gaged in by the scientific community,” which fails to
transform the claim into “significantly more than a patent
upon the” ineligible concept itself. Mayo, 132 S. Ct. at
1298, 1294.
                             A
    We begin with step one: whether the claims here are
8        RAPID LITIGATION MANAGEMENT    v. CELLZDIRECT, INC.



“directed to” a patent-ineligible concept. The district
court concluded that they were: that “the patent is di-
rected to an ineligible law of nature: the discovery that
hepatocytes are capable of surviving multiple freeze-thaw
cycles.” Celsis, 83 F. Supp. 3d at 783. We disagree.
    Claim 1 recites a “method of producing a desired
preparation of multi-cryopreserved hepatocytes.” ’929
patent col. 19 l. 56-col. 20 l. 20. The method requires an
artisan to carry out a number of concrete steps to achieve
the desired preparation: step (A) requires performing
density gradient fractionation on a set of previously
frozen and thawed cells to separate out the viable ones;
step (B) requires recovering the separated viable cells;
and step (C) requires cryopreserving the recovered cells.
The end result is a preparation of multi-cryopreserved
cells that can be thawed for immediate use, retaining 70%
viability. Claim 5 adds to the method, reciting “a pooled
preparation of hepatocytes of multiple sources.” Id. at col.
20 ll. 31-33. The resulting preparation, and the process
for creating it, achieved a notable advance over prior art
techniques for preserving hepatocytes. J.A. 2513-14.
    The district court identified in these claims what it
called a “natural law”—the cells’ capability of surviving
multiple freeze-thaw cycles. We need not decide in this
case whether the court’s labeling is correct. It is enough
in this case to recognize that the claims are simply not
directed to the ability of hepatocytes to survive multiple
freeze-thaw cycles. Rather, the claims of the ’929 patent
are directed to a new and useful laboratory technique for
preserving hepatocytes. This type of constructive process,
carried out by an artisan to achieve “a new and useful
end,” is precisely the type of claim that is eligible for
patenting. Alice, 134 S. Ct. at 2354 (quoting Gottschalk v.
Benson, 409 U.S. 63, 67 (1972)). The inventors certainly
discovered the cells’ ability to survive multiple freeze-
thaw cycles, but that is not where they stopped, nor is it
what they patented. Rather, “as the first party with
RAPID LITIGATION MANAGEMENT   v. CELLZDIRECT, INC.        9



knowledge of” the cells’ ability, they were “in an excellent
position to claim applications of that knowledge.” Myriad,
133 S. Ct. at 2120 (quoting Ass’n for Molecular Pathology
v. U.S. Patent & Trademark Office, 689 F.3d 1303, 1349
(Fed. Cir. 2012) (Bryson, J., concurring in part and dis-
senting in part)). That is precisely what they did. They
employed their natural discovery to create a new and
improved way of preserving hepatocyte cells for later use.
    The claims in this case are immediately distinguisha-
ble from those we have found patent ineligible in cases
since Mayo and Alice. In recent cases, we found claims
“directed to” a patent-ineligible concept when they
amounted to nothing more than observing or identifying
the ineligible concept itself. For example, in Genetic
Technologies, the claim recited methods for detecting a
coding region of DNA based on its relationship to non-
coding regions. Genetic Techs., Ltd. v. Merial L.L.C., 818
F.3d at 1369, 1373-74 (Fed. Cir. 2016). Because the
relationship between coding and non-coding sequences
was a law of nature, the claim amounted to nothing other
than identifying “information about a patient’s natural
genetic makeup.” Id. at 1375. Likewise in Ariosa, the
claims recited methods for detecting paternally inherited
cffDNA in the blood or serum of a pregnant female.
Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371,
1373-74 (Fed. Cir. 2015), cert. denied, No. 15-1102, 2016
WL 1117246 (June 27, 2016). The existence and location
of cffDNA is a natural phenomenon; identifying its pres-
ence was merely claiming the natural phenomena itself.
Id. at 1376. And in In re BRCA, the claims recited meth-
ods for screening human germline for an altered BRCA1
gene by comparing the target DNA sequence with wild-
type sequence. In re BRCA1- & BRCA2-Based Hereditary
Cancer Test Patent Litig., 774 F.3d 755, 761-62 (Fed. Cir.
2014). But comparing two sequences to detect alterations
is a patent-ineligible “abstract mental process.” Id. at
763. Although the claims in each of these cases employed
10       RAPID LITIGATION MANAGEMENT    v. CELLZDIRECT, INC.



method steps, the end result of the process, the essence of
the whole, was a patent-ineligible concept.
    The same is not true here. The end result of the ’929
patent claims is not simply an observation or detection of
the ability of hepatocytes to survive multiple freeze-thaw
cycles. Rather, the claims are directed to a new and
useful method of preserving hepatocyte cells. Indeed, the
claims recite a “method of producing a desired prepara-
tion of multi-cryopreserved hepatocytes.” ’929 patent col.
19 l. 56-col. 20 l. 20 (emphasis added). Through the
recited steps, the patented invention achieves a better
way of preserving hepatocytes. The ’929 patent claims
are like thousands of others that recite processes to
achieve a desired outcome, e.g., methods of producing
things, or methods of treating disease. That one way of
describing the process is to describe the natural ability of
the subject matter to undergo the process does not make
the claim “directed to” that natural ability. If that were
so, we would find patent-ineligible methods of, say, pro-
ducing a new compound (as directed to the individual
components’ ability to combine to form the new com-
pound), treating cancer with chemotherapy (as directed
to cancer cells’ inability to survive chemotherapy), or
treating headaches with aspirin (as directed to the human
body’s natural response to aspirin).
    Our conclusion applies even more so to claim 5, which
requires the additional step of pooling hepatocytes from
multiple donors. Conventional preparation methods were
unable to create a frozen hepatocyte preparation that
could be stored for a long duration and then, upon thaw-
ing, result in a pool of hepatocytes from multiple donors
with viability upwards of 70%. Because the claimed
process involves both multiple freeze-thaw cycles and
pooling cells from various donors, it results in a prepara-
tion that is both new and vastly more useful for research
than hepatocyte preparations made by conventional
methods.
RAPID LITIGATION MANAGEMENT   v. CELLZDIRECT, INC.      11



    LTC asserts that claim 5, including the additional re-
quirement of pooling of hepatocyte cells, is indistinguish-
able from the claims held patent ineligible in Funk Bros.
Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948). There the
Supreme Court held that a mixture of different bacterial
species was not patent eligible because “[n]o species
acquires a different use,” “[e]ach species has the same
effect it always had,” and “[t]he bacteria perform in their
natural way.” Id. at 131. But Funk Bros. involved prod-
uct claims, and the court explicitly noted that it was not
“presented [with] the question whether the methods of
selecting and testing the non-inhibitive strains are pa-
tentable.” Id. at 130. Here, regardless of whether the
individual hepatocytes in the pool of multi-cryopreserved
hepatocytes have the same effect they always had or
perform in their natural way, the claims are directed to a
new and useful process of creating that pool, not to the
pool itself.
    Nor is LTC correct in arguing that the claims of the
’929 patent are just like the isolated DNA found un-
patentable in Myriad, 133 S. Ct. 2107, or the methods of
detecting cffDNA found unpatentable in Ariosa, 788 F.3d
1371. In Myriad, while holding the composition claims to
isolated DNA patent ineligible, the Supreme Court stated:
“It is important to note what is not implicated by this
decision. First, there are no method claims before this
Court. Had Myriad created an innovative method of
manipulating genes while searching for the BRCA1 and
BRCA2 genes, it could have possibly sought a method
patent. But the processes used by Myriad to isolate DNA
were well understood . . . and are not at issue in this
case.” 133 S. Ct. at 2119-20. Here, the inventors devel-
oped an innovative method of manipulating hepatocytes,
a particular kind of liver cell which, prior to this inven-
tion, had been very difficult to preserve for future use.
See id. The claims are thus distinguishable from those
held unpatentable in Myriad. They are also distinguisha-
12        RAPID LITIGATION MANAGEMENT    v. CELLZDIRECT, INC.



ble from those held unpatentable in Ariosa, 788 F.3d
1371. Although the claims in Ariosa were also written as
process claims, the court concluded that they were “di-
rected to” the patent-ineligible cffDNA itself. Id. at 1376.
The claims of the ’929 patent, as explained above, are not
similarly infirm.
    We are also not persuaded by LTC’s conjecture that, if
the claimed multi-cryopreservation process is sufficient to
imbue the ’929 patent claims with patent-eligibility, “then
any frozen or preserved cell, bacteria, or other product of
nature would be patent eligible.” Appellees’ Br. 24. Not
so. It is the process of preservation that is patent eligible
here, not necessarily the end product. In any event,
LTC’s argument proves too much: if LTC were correct, no
one could ever get a patent on cryopreservation, or on any
other innovative method that acts on something that is
naturally occurring, simply because of the nature of the
underlying subject matter. Section 101 is not so narrow.
     LTC argues that our approach improperly shoehorns
the step two analysis into step one: that focusing on the
claims’ application of the cells’ ability to survive multiple
freeze-thaw cycles in a new preservation process properly
falls under step two’s inquiry into “whether the additional
elements ‘transform the nature of the claim’ into a patent-
eligible application.” See Alice, 134 S. Ct. at 2355 (quot-
ing Mayo, 132 S. Ct. at 1297). But it is LTC’s approach,
not ours, that collapses the inquiry into a single step.
Under the Supreme Court’s test, some claims will be
“directed to” a patent-ineligible concept and some, neces-
sarily, will not. This is true even if “all inventions at
some level embody, use, reflect, rest upon, or apply laws
of nature, natural phenomena, or abstract ideas.” Mayo,
132 S. Ct. at 1293. As the Supreme Court has made clear,
“an invention is not rendered ineligible for patent simply
because it involves” one of the patent-ineligible concepts.
Alice, 134 S. Ct. at 2354. Indeed, to preclude the patent-
ing of an invention simply because it touches on some-
RAPID LITIGATION MANAGEMENT   v. CELLZDIRECT, INC.       13



thing natural would “eviscerate patent law.” Mayo, 132 S.
Ct. at 1293.
    At step one, therefore, it is not enough to merely iden-
tify a patent-ineligible concept underlying the claim; we
must determine whether that patent-ineligible concept is
what the claim is “directed to.” Here, the plain claim
language shows that it is not. The ’929 patent does not
simply claim hepatocytes’ ability to survive multiple
freeze-thaw cycles. The ’929 patent instead claims a
“method of producing a desired preparation of multi-
cryopreserved hepatocytes.” ’929 patent col. 19 l. 56-col.
20 l. 20. This new and improved technique, for producing
a tangible and useful result, falls squarely outside those
categories of inventions that are “directed to” patent-
ineligible concepts.
                             B
    Even if LTC were correct that the ’929 patent is
“directed to” hepatocytes’ natural ability to survive multi-
ple freeze-thaw cycles, and that we must proceed to step
two, we would find the claims patent-eligible at that point
as well. Under step two, claims that are “directed to” a
patent-ineligible concept, yet also “improve[] an existing
technological process,” are sufficient to “transform[] the
process into an inventive application” of the patent-
ineligible concept. Alice, 134 S. Ct. at 1358 (quoting
Mayo, 132 S. Ct. at 1299) (discussing Diamond v. Diehr,
450 U.S. 175 (1981). The claims of the ’929 patent do
precisely that: they recite an improved process for pre-
serving hepatocytes for later use. The benefits of the
improved process over the prior art methods are signifi-
cant. The claimed method is used to create hepatocyte
preparations that no longer exhibit unacceptable loss of
viability. And it allows researchers to pool samples
together in advance and preserve them for later use,
rather than needing to wait until enough single samples
are accumulated that can be pooled and used immediate-
14       RAPID LITIGATION MANAGEMENT    v. CELLZDIRECT, INC.



ly. The claimed method is patent eligible because it
applies the discovery that hepatocytes can be twice frozen
to achieve a new and useful preservation process. See
Mayo, 132 S. Ct. at 1293-94 (“[A]n application of a law of
nature or mathematical formula to a known structure or
process may well be deserving of patent protection.”)
(quoting Diehr, 450 U.S. at 187).
    That each of the claims’ individual steps (freezing,
thawing, and separating) were known independently in
the art does not make the claim unpatentable. It is true
that, at step two, a claim that recites only “well-
understood, routine, conventional activity already en-
gaged in by the scientific community” will not be patent
eligible. Mayo, 132 S. Ct. at 1298. Thus, in Mayo, the
claims failed step two because the steps of administering
the drug, measuring metabolite levels, and adjusting
dosage were already being performed by those in the field;
adding knowledge of the natural law was insufficient to
render the claims patent eligible. Id. Likewise in Ariosa,
the steps of preparing, amplifying, and detecting genetic
sequences were already being done; performing those
same steps on a newly discovered, naturally-occurring
substrate (cffDNA in maternal plasma or serum) did not
rise to the level of an inventive concept. 788 F.3d at 1377-
78. That is not to say, however, that all process claims
that employ only independently known steps will be
unpatentable. To the contrary, in examining claims
under step two, we must view them as a whole, consider-
ing their elements “both individually and ‘as an ordered
combination.’” Alice, 134 S. Ct. at 2355 (quoting Mayo,
132 S. Ct. at 1298). Thus, “a new combination of steps in
a process may be patentable even though all the constitu-
ents of the combination were well known and in common
use before the combination was made.” Diehr, 450 U.S. at
188.
    Here, the claimed process involves freezing and thaw-
ing hepatocytes twice. The individual steps of freezing
RAPID LITIGATION MANAGEMENT     v. CELLZDIRECT, INC.         15



and thawing were well known, but a process of preserving
hepatocytes by repeating those steps was itself far from
routine and conventional. As the examiner noted when
allowing the patent, “[t]he prior art only discloses meth-
ods having one freeze-thaw cycle of hepatocytes, wherein,
upon thawing, a gradient centrifugation step is required
to remove the non-viable cells.” J.A. 2513-14 (emphasis
added). Likewise, during reexamination, the examiner
explained that “[t]he prior art evidence[d] cellular damage
produced by cryopreservation, and a lack of any experi-
mentation with multiply cryopreserved cells.” J.A. 7157
(emphasis added). We made similar observations earlier
in this litigation, noting that “the prior art taught away
from multiple freezings,” as “[a] single round of freezing
severely damages hepatocyte cells and results in lower
cell viability.” Celsis In Vitro, Inc. v. CellzDirect, Inc., 664
F.3d 922, 928 (Fed. Cir. 2012); see also id. (stating that
“the present invention is in an art well-known for its
unpredictability” and the “art was a crowded field for
many years and yet there was not one reference to multi-
cryopreservation”). As aptly summarized by the district
court: “Prevailing wisdom . . . taught that cells could be
frozen only once and then had to be used or discarded.”
Celsis, 83 F. Supp. 3d at 777-78.
     Repeating a step that the art taught should be per-
formed only once can hardly be considered routine or
conventional. This is true even though it was the inven-
tor’s discovery of something natural that led them to do
so. Just as in Diehr, it is the particular “combination of
steps” that is patentable here. 450 U.S. at 188. The
inventors discovered that some percentage of hepatocytes
can survive multiple freeze-thaw cycles and applied that
discovery to improve existing methods for preserving
hepatocytes. To require something more at step two
would be to discount the human ingenuity that comes
from applying a natural discovery in a way that achieves
16        RAPID LITIGATION MANAGEMENT    v. CELLZDIRECT, INC.



a “new and useful end.” Alice, 134 S. Ct. at 2354 (quoting
Gottschalk, 409 U.S. at 67).
                             C
    We end with two additional points. First, the crux of
LTC’s argument seems to be that, once it was discovered
that hepatocytes could survive multiple freeze-thaw
cycles, it would have been a simple task to repeat the
known freeze-thaw process to arrive at the claimed inven-
tion. But patent-eligibility does not turn on ease of execu-
tion or obviousness of application. Those are questions
that are examined under separate provisions of the Pa-
tent Act. Mayo, 132 S. Ct. at 1304. 2
    Second, while pre-emption is not the test for deter-
mining patent-eligibility, Ariosa, 788 F.3d at 1378-79, it is
certainly the “concern that undergirds . . . § 101 jurispru-
dence,” Alice, 134 S. Ct. at 2358. Here, while not resting
our opinion on them, we note the district court’s findings
that the ’929 patent “does not lock up the natural law in
its entirety” and that “LTC has already managed to
engineer around the patent.” Celsis, 83 F. Supp. 3d at
785. These findings accord with our conclusion that the




     2  Indeed, the obviousness of the ’929 patent claims
under 35 U.S.C. § 103 has been addressed in prior pro-
ceedings. During original examination, and then again
during post-grant reexamination, the U.S. Patent and
Trademark Office found the claims non-obvious given the
knowledge that cryopreservation damages cells and the
prior art’s lack of experimentation with multi-
cryopreserved cells. J.A. 2513-14; J.A. 7157. On a prelim-
inary record, we made similar observations in affirming
the district court’s entry of preliminary injunction. See
Celsis, 664 F.3d at 928 (noting that “the prior art taught
away from multiple freezings”).
RAPID LITIGATION MANAGEMENT   v. CELLZDIRECT, INC.   17



patent is not “directed to” a patent-ineligible building
block of human ingenuity.
                           III
    Because the ’929 patent claims are not directed to a
patent-ineligible concept, we vacate and remand for
further proceedings consistent with this opinion.
            VACATED AND REMANDED
                          COSTS
   Costs to appellants.
