Document ID: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-15-01570/USCOURTS-ca13-15-01570-0/pdf.json

Parties Involved:
CellzDirect, Inc.
Appellee
Celsis Holdings, Inc.
Appellant
In Vitro, Inc.
Appellant
Invitrogen Corporation
Appellee
Rapid Litigation Management Ltd.
Appellant

Document Text:

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, Washington, 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. 

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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 Organization. Also represented by BRADLEY JOHN OLSON, Washington, 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 summary 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 hepatocytes are capable of surviving multiple freeze-thaw cycles—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 number of attributes useful for testing, diagnostic, and treatment purposes. For example, hepatocytes can be used to 

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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 developed “cryopreservation” techniques to preserve hepatocytes for later use. Id. at col. 2 ll. 36-40. These methods 

generally comprised freezing hepatocytes at frigid temperatures; then, when needed, thawing them and recovering 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 problems, however. It was understood that the process could 

damage the hepatocytes, leading to poor recovery numbers of viable cells. Id. at col. 3 ll. 5-32. Furthermore, 

these prior methods were unsuitable for preparing multidonor hepatocyte pools. Id. at col. 3 ll. 33-60. Because 

hepatocytes from different donors generally have different 

metabolic properties, researchers desired to pool hepatocytes 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 because 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 cryopreservation 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. 

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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 comprises: (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, exhibiting 70% viability after the second thaw. Id. 

The ’929 patented process has a number of advantages over the prior art. By separating out and refreezing only the viable cells, the preserved hepatocyte 

preparations can be thawed and used later without unacceptable 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 refrozen 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 comprises multi-cryopreserved, pooled hepatocyte preparations useful for a wide variety of research purposes. 

Claim 1 is representative of the ’929 patent. It recites:

1. A method of producing a desired preparation of 

multi-cryopreserved hepatocytes, said hepatocytes being capable of being frozen and thawed 

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at least two times, and in which greater than 

70% of the hepatocytes of said preparation are 

viable after the final thaw, said method comprising:

(A) subjecting hepatocytes that have been frozen and thawed to density gradient fractionation to separate viable hepatocytes from nonviable hepatocytes, 

(B) recovering the separated viable hepatocytes, 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 preparation comprises a pooled preparation of hepatocytes 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 Management Ltd. and In Vitro, Inc. (collectively, “IVT”), and 

 

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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 concluded 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 concept,” observing that, upon discovering the cells’ capability 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”).

 

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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 predecessors . . . 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) (quoting Mayo, 132 S. Ct. at 1301). 

The Supreme Court has recently articulated a twopart test for distinguishing patents that claim one of the 

patent-ineligible exceptions from those that claim patenteligible 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 concepts.” 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, considered 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 “wellunderstood, routine, conventional activity already engaged 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 

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“directed to” a patent-ineligible concept. The district 

court concluded that they were: that “the 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. 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 freezethaw cycles, but that is not where they stopped, nor is it 

what they patented. Rather, “as the first party with 

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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 dissenting 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 distinguishable 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 noncoding 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 presence was merely claiming the natural phenomena itself. 

Id. at 1376. And in In re BRCA, the claims recited methods for screening human germline for an altered BRCA1 

gene by comparing the target DNA sequence with wildtype 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 

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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 preparation 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, producing a new compound (as directed to the individual 

components’ ability to combine to form the new compound), 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 thawing, 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 preparation that is both new and vastly more useful for research 

than hepatocyte preparations made by conventional 

methods. 

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LTC asserts that claim 5, including the additional requirement of pooling of hepatocyte cells, is indistinguishable 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 product 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 patentable.” 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 unpatentable 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 developed an innovative method of manipulating hepatocytes,

a particular kind of liver cell which, prior to this invention, 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 distinguishaCase: 15-1570 Document: 83-2 Page: 11 Filed: 07/05/2016
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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 “directed 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 patenteligible application.” See Alice, 134 S. Ct. at 2355 (quoting 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, necessarily, 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 patenting of an invention simply because it touches on someCase: 15-1570 Document: 83-2 Page: 12 Filed: 07/05/2016
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thing natural would “eviscerate patent law.” Mayo, 132 S. 

Ct. at 1293. 

At step one, therefore, it is not enough to merely identify 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 multicryopreserved 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” patentineligible concepts. 

B 

Even if LTC were correct that the ’929 patent is

“directed to” hepatocytes’ natural ability to survive multiple 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 patentineligible 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 preserving hepatocytes for later use. The benefits of the 

improved process over the prior art methods are significant. 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 immediateCase: 15-1570 Document: 83-2 Page: 13 Filed: 07/05/2016
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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 “wellunderstood, routine, conventional activity already engaged 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, considering 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 constituents 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 thawing hepatocytes twice. The individual steps of freezing 

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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 methods 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 experimentation 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 multicryopreservation”). 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 performed only once can hardly be considered routine or 

conventional. This is true even though it was the inventor’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 

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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 invention. But patent-eligibility does not turn on ease of execution or obviousness of application. Those are questions 

that are examined under separate provisions of the Patent Act. Mayo, 132 S. Ct. at 1304.2 

Second, while pre-emption is not the test for determining patent-eligibility, Ariosa, 788 F.3d at 1378-79, it is 

certainly the “concern that undergirds . . . § 101 jurisprudence,” 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 proceedings. 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 multicryopreserved cells. J.A. 2513-14; J.A. 7157. On a preliminary 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”). 

 

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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. 

Case: 15-1570 Document: 83-2 Page: 17 Filed: 07/05/2016