Lawrence Livermore National Security, LLC

Patent Trials and Appeals Board

Nov 17, 2020

14452453 - (D) (P.T.A.B. Nov. 17, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/452,453 08/05/2014 Heeral Sheth LLNLP125/IL-12754 3160
78980 7590 11/17/2020
LLNL/Zilka-Kotab
Lawrence Livermore National Laboratory
L-703, P.O. Box 808
Livermore, CA 94551
EXAMINER
MCNEIL, STEPHANIE A N
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
11/17/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
llnl-docket@llnl.gov
zk-uspto@zilkakotab.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HEERAL SHETH, MARGARET WINDY MCNERNEY,
SATINDERPALL S. PANNU, and ELIZABETH K. WHEELER
__________

Appeal 2020-002478
Application 14/452,453
Technology Center 1600
__________

Before FRANCISCO C. PRATS, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134 involving claims to a tissue
system composed of reconstituted human extracellular matrix with a
vascular network. The Examiner rejected the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse and enter new grounds of
rejection.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Real Party in Interest as Lawrence
Livermore National Security, LLC. (See Appeal Br. 2).
2 We have considered the Specification of Aug. 5, 2014 (“Spec.”); Final
Office Action of Mar. 15, 2019 (“Final Action”); Appeal Brief of Aug. 19,
2019 (“Appeal Br.”); Examiner’s Answer of Dec. 10, 2019 (“Ans.”); and
Reply Brief of Feb. 6, 2020 (“Reply Br.”).
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Statement of the Case
Background
“[M]any recent tissue engineering developments focus on either a
simplified two-dimensional (2D) or three-dimensional (3D) representation of
a tissue system” but “two-dimensional applications are of limited relevance
to clinical studies because the 2D monolayer of tissue formed thereby does
not represent true physiological conditions” (Spec. ¶¶ 7–8). “[T]o overcome
this limitation, a vascular network for delivering nutrients and carrying away
waste, e.g. as observed in vivo, is necessary. . . . In many cases, thick,
multilayered tissue systems are needed to adequately represent the complex
physiology of human organs in-vivo” (id. ¶ 9).
“[C]onventional approaches extend to three-dimensional tissue
systems. . . . Living cells and the scaffold or lattice are both encapsulated in
an extracellular matrix (ECM), and subsequently the lattice material may be
dissolved to leave voids representing a simplified, nonphysiological network
of channels” (Spec. ¶ 10). “Disadvantageously, such simplified lattices and
scaffolds do not represent physiological conditions observed in vivo” (id. ¶
11). “Currently available cell culture techniques and instrumentation have
not demonstrated any such ability to fuse discrete channels into a
functioning vascular network much less a functioning vascular network
characterized by a physiologically relevant, three-dimensional arrangement”
(id. ¶ 15).
The Claims
Claims 1–11, 21, and 23–29 are on appeal. Claims 1 and 29 are
representative and read as follows:
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1. A tissue system, comprising:
an optically transparent support material comprising
reconstituted human extracellular matrix (ECM); and
a vascular network comprising a plurality of channels
disposed in the support material,
wherein the vascular network is physiologically relevant;
and
wherein at least some of the channels are structurally
arranged according to an artificial, predefined three-
dimensional pattern.

29. A tissue system, comprising:
a support material; and
a vascular network comprising a plurality of channels
disposed in the support material, wherein at least some of the
channels are structurally arranged according to an artificial,
predefined three-dimensional pattern;
wherein the vascular network is physiologically relevant,
and has physical characteristics of being formed from
omnidirectional printing of a bioink into the support material;
and
wherein the physical characteristics of being formed from
omnidirectional printing of the bioink into the support material
comprise at least some of the channels being printed as a
multilayer coaxial structure, the multilayer coaxial structure
comprising an interior cavity surrounded by a first layer
comprising endothelial cells, the first layer being surrounded by
a second layer comprising smooth muscle cells, and the second
layer being surrounded by a third layer comprising fibroblasts.

The Rejections
A. The Examiner rejected claims 1–11, 21, 23–26, and 28 under U.S.C.
§ 103(a) as obvious over Vacanti,3 Ferris,4 and Tibbitt5 (Final Act. 3–6).

3 Vacanti et al., US 6,176,874 B1, issued Jan. 23, 2001.
4 Ferris et al., Biofabrication: an overview of the approaches used for
printing of living cells, 97 Appl. Microbiol. Biotechnol. 4243–58 (2013).
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B. The Examiner rejected claims 27 and 29 under U.S.C. § 103(a) as
obvious over Vacanti, Ferris, and Alberts6 (Final Act. 6–7).
Because the same issue of claim interpretation is relevant to both of
these rejections, we will consider these rejections together.
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that Vacanti,
Ferris, and Tibbitt render the claims obvious?
Findings of Fact
1. Vacanti teaches “[t]issue engineering has emerged as a
scientific field which has the potential to aid in human therapy by producing
anatomic tissues and organs for the purpose of reconstructive surgery and
transplantation” (Vacanti 1:54–57).
2. Vacanti teaches:
Solid free-form fabrication (SFF) methods are used to
manufacture devices for allowing tissue regeneration and for
seeding and implanting cells to form organ and structural
components, which can additionally provide controlled release
of bioactive agents, wherein the matrix is characterized by a
network of lumens functionally equivalent to the naturally
occurring vasculature of the tissue formed by the implanted
cells, and which can be lined with endothelial cells and coupled
to blood vessels or other ducts at the time of implantation to
form a vascular or ductile network throughout the matrix. As
defined herein, SFF refers to any manufacturing technique that
builds a complex three dimensional object as a series of two
dimensional layers. The SFF methods can be adapted for use
with a variety of polymeric, inorganic and composite materials

5 Tibbitt et al., Hydrogels as Extracellular Matrix Mimics for 3D Cell
Culture, 103 Biotechnology and Bioengineering 655–63 (2009).
6 Alberts et al., Molecular Biology of the Cell, https://www.ncbi.nlm.
nih.gov/books/NBK26848/, 1–5 (New York: Garland Science (2002).
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to create structures with defined compositions, strengths, and
densities, using computer aided design (CAD).
(Vacanti 2:62 to 3:11).
3. Vacanti teaches:
Blood vessels are designed to imitate the parameters of
the naturally occurring vascular structure. The diameter of the
lumens is increased to compensate for the thickness of the
subsequently seeded endothelial cells proliferate to cover the
lumen walls. In the preferred embodiment using biodegradable
polymer to form the matrix, the matrix eventually degrades to
leave only the seeded cells forming blood vessels that are
virtually indistinguishable from natural blood vessels. Standard
methodology is unable to accomplish the necessary level of
detail required to form blood vessel equivalents; this is not a
problem with the solid free form techniques since the level of
resolution is so small. The blood vessel lumens are
interconnected throughout the matrix so that one or more inlets
can be anastomized to one or more arteries at the time of
implantation, and one or more outlets anastomized to one or
more veins.
(Vacanti 17:33–48).
4. Vacanti teaches that a “number of materials are commonly used
to form a matrix. Unless otherwise specified, the term ‘polymer’ will be
used to include any of the materials used to form the matrix, including . . . a
protein polymer, for example, albumin or collagen, or a polysaccharide”
(Vacanti 8:12–25).
5. Tibbitt teaches “[n]atural gels for cell culture are typically
formed of proteins and ECM components such as collagen” (Tibbitt 657,
col. 2).
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6. Ferris teaches:
approaches based on the principle of laser-induced forward
transfer (LIFT). This technique was initially developed for the
direct writing of metal features using a high-energy pulsed laser
to deposit a metal film on an optically transparent support . . .
Modifications of the LIFT technique to deposit biological
materials, including cells, have collectively been described as
laser-assisted bioprinting (LAB) techniques.
(Ferris 4246, col. 2; citations omitted).
7. The Specification teaches “cells and the scaffold or lattice are
both encapsulated in an extracellular matrix (ECM), and subsequently the
lattice material may be dissolved to leave voids representing a simplified,
nonphysiological network of channels for exchanging and/or communicating
nutrients, waste, signals, drugs, etc. between the tissue system and the
external environment” (Spec. ¶ 10).
8. The Specification teaches “support material 104 may comprise
a matrix substantially representing an extracellular matrix, in preferred
embodiments, and more preferably comprises lyophilized, reconstituted
human cardiac extracellular matrix and/or components thereof” (Spec. ¶ 49).
9. Frantz7 teaches “fundamentally, the ECM is composed of
water, proteins and polysaccharides” (Frantz 4195, col. 3).
10. Frantz teaches “ECM is composed of two main classes of
macromolecules: proteoglycans (PGs) and fibrous proteins . . . The main
fibrous ECM proteins are collagens, elastins, fibronectins and laminins . . .
PGs fill the majority of the extracellular interstitial space within the tissue in
the form of a hydrated gel” (Frantz 4196, col. 1; citations omitted).

7 Frantz et al., The extracellular matrix at a glance, 123 J. Cell Science
4195–200 (2010).
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Principles of Law
Although we apply the broadest reasonable interpretation during
examination, “[a]bove all, the broadest reasonable interpretation must be
reasonable in light of the claims and specification.” PPC Broadband, Inc. v.
Corning Optical Commc’ns RF, LLC, 815 F.3d 747, 755 (Fed. Cir. 2016).
A prima facie case for obviousness “requires a suggestion of all
limitations in a claim,” CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333,
1342 (Fed. Cir. 2003) and “a reason that would have prompted a person of
ordinary skill in the relevant field to combine the elements in the way the
claimed new invention does.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
Analysis
Claim Construction
We begin with claim interpretation, since before a claim is properly
interpreted, its scope cannot be compared to the prior art. The phrase at
issue in Claim 1 is the phrase “reconstituted human extracellular matrix”.
The Examiner finds “the broadest reasonable interpretation of a
reconstituted extracellular matrix includes extracellular matrixes that
comprise components of extracellular matrices” and therefore a matrix
composed of collagen “reads on the broadest reasonable interpretation of
‘reconstituted human extracellular matrix’” (Ans. 8).
Appellant contends “although human ECM includes collagen,
collagen itself is not reconstituted human ECM. For instance, collagen is
also a major component of bone, teeth, muscle and connective tissue, and
many other tissues/systems without being present specifically in the form of
ECM, much less reconstituted human ECM” (Appeal Br. 6).
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We first turn to the Specification which is, “[i]n most cases, the best
source for discerning the proper context of claim terms.” Metabolite Labs.,
Inc. v. Lab. Corp. of Am. Holdings, 370 F.3d 1354, 1360 (Fed. Cir. 2004).
The Specification has limited discussion regarding ECM, but does state that
“support material 104 may comprise a matrix substantially representing an
extracellular matrix, in preferred embodiments, and more preferably
comprises lyophilized, reconstituted human cardiac extracellular matrix
and/or components thereof” (FF 8). This teaching distinguishes between
reconstituted human cardiac ECM and ECM components as being sufficient
to represent “an extracellular matrix”, suggesting that these are different,
though they may be used together. Thus, the intrinsic evidence provides
some support, although not unambiguously, for Appellant’s position that
collagen itself would not have been understood as reconstituted human
ECM.
Thus, we next turn to the extrinsic evidence of Frantz, cited by
Appellant, that teaches: “ECM is composed of two main classes of
macromolecules: proteoglycans (PGs) and fibrous proteins . . . The main
fibrous ECM proteins are collagens, elastins, fibronectins and laminins” (FF
10). Frantz therefore understands ECM to be minimally composed of at
least two things, proteoglycans and proteins (see FF 9–10).
In light of the foregoing evidence, we find that Appellant has the
better position regarding the broadest reasonable interpretation of
reconstituted human ECM as recited in claim 1. The Specification suggests
that “reconstituted extracellular matrix” is an entity that is different from
individual isolated ECM components, and claim 1 recites “reconstituted
human extracellular matrix”. Indeed, the most straightforward interpretation
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of reconstituted human extracellular matrix in claim 1 is that it requires
naturally occurring human extracellular matrix with all of the naturally
occurring components. Therefore, the absence of any recitation of
components in claim 1 in combination with Frantz’s teaching that ECM is
commonly understood to be composed of at least proteins and
proteoglycans, provides a basis for understanding “reconstituted human
extracellular matrix” in claim 1 as requiring all of the naturally occurring
components of human extracellular matrix.
It is undisputed that Vacanti does not teach naturally occurring human
extracellular matrix and the Examiner does not rely upon a reference
suggesting that the collagen or other matrix components of Vacanti be
replaced or substituted with human extracellular matrix or that human
extracellular matrix would have been an obvious equivalent of the matrix
components of Vacanti. Neither Tibbitt nor Ferris are relied upon for this
teaching.
Therefore, in the absence of any teaching in the relied upon prior art
to form the tissue system of claim 1 using reconstituted naturally occurring
human extracellular matrix, we reverse this rejection.
Conclusion of Law
A preponderance of the evidence of record does not support the
Examiner’s conclusion that Vacanti, Ferris, and Tibbitt render the claims
obvious. We find the same result applies for the combination of Vacanti,
Ferris, and Alberts.

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New Grounds of Rejection
Under the provisions of 37 C.F.R. § 41.50(b), we enter the following
new grounds of rejection.
We reject claims 1 and 29 under 35 U.S.C. § 102(b) as anticipated by
Fronheiser8 as evidenced by Histology Guide9 and Kloc.10 As the Board’s
function is primarily one of review and not search, we leave to the Examiner
the determination of whether this evidence alone or in combination with
additional prior art addresses the dependent claims.
We also note that a publication dated after an Appellant’s filing date is
acceptable as evidence of characteristics of prior art products. See In re
Wilson, 311 F.2d 266, 268–269 (CCPA 1962) (“The board considered that
the publication was properly cited to show a state of fact. After reading the
entire publication, so do we.”)
We also reject claims 1 and 29 under 35 U.S.C. § 101 as directed to
non-statutory subject matter.

35 U.S.C. § 102(b) over Fronheiser, as evidenced by Histology Guide and
Kloc
Findings of Fact
11. Fronheiser teaches a tissue system comprising “cross sections

8 Fronheiser, Real-time optoacoustic monitoring and three-dimensional
mapping of a human arm vasculature, 15 J. Biomedical Optics 1–7 (2010).
9 Histology Guide, Extracellular Matrix, University of Leeds,
https://www.histology.leeds.ac.uk/tissue_types/connective/connective_groun
dS.php (accessed Nov. 6, 2020).
10 Kloc et al., Chronic allograft rejection: A significant hurdle to transplant
success, 2 Burns & Trauma 3–10 (2014).
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of the ulnar and radial arteries in the region of the wrist” (Fronheiser 3, col.
1).
12. Figure 2 of Fronheiser is reproduced below:

“Fig. 2 Schematic showing the scanning locations for the two experiments”
(Fronheiser 2, col. 2).
13. Fronheiser teaches: “We showed an ability to clearly visualize
the main vascular structure in the forearm in real-time 2-D slices and in a
reconstructed volume that showed a more complete view of the vascular
network” (Fronheiser 4, col. 2).
14. Histology Guide teaches “extracellular matrix is an amorphous
gelatinous material. It is transparent, colourless, and fills the spaces between
fibres and cells” (Histology Guide 1).
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15. Figure 1 of Kloc is reproduced below:

Figure 1: Blood vessel composition. Large blood (arteries and
veins) vessels are composed of three layers (shown here out of
proportion). Tunica intima (the thinnest layer, facing the blood)
contains a single layer of endothelial cells positioned on
subendothelial extracellular matrix and circularly arranged
elastic bands called the internal elastic lamina. Tunica media
(which is the thickest layer in arteries) is composed of
extracellular matrix, smooth muscle cells (SMCs) and thick
elastic band called external elastic lamina. Tunica adventitia
(which is the thickest layer in veins) is made of connective
tissue with interspersed fi broblasts and stem/progenitor cells.
(Kloc 4, col. 1).
Principles of Law
Anticipation under 35 U.S.C. § 102 requires that “each and every
element as set forth in the claim is found, either expressly or inherently
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described, in a single prior art reference.” In re Robertson, 169 F.3d 743,
745 (Fed. Cir. 1999).
Analysis
We again begin with claim interpretation in order to compare the
claim to the prior art. The following terms in claims 1 and 29 are material to
our prior art analysis: “physiologically relevant,” “reconstituted,”
“artificial,” “predefined,” and “characteristics of being formed from
omnidirectional printing.”
The only term expressly defined by the Specification is
“physiologically relevant” which “is a network of vascular channels that
substantially represents the vascular network observed in human physiology
in vivo” (Spec. ¶ 36). Therefore, consistent with the definition, we interpret
this term as any vascular network identical or similar to an in vivo human
network.
All of the remaining terms noted represent process limitations with
respect to material that forms a part of the “tissue system” claimed. Neither
the Specification nor Appellant identify any structural differences between a
naturally occurring human tissue that includes naturally occurring ECM and
has a naturally occurring vascular network that includes a three-dimensional
pattern of channels and a tissue formed from “reconstituted human
extracellular matrix,” from a vascular network that is “artificial” or
“predefined,” or from a vascular network that has “characteristics of being
formed from omnidirectional printing.”
“It has long been established that one cannot avoid anticipation by an
earlier product disclosure by claiming the same product more narrowly, that
is, by claiming the product as produced by a particular process.” SmithKline
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Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1317 (Fed. Cir. 2006). The
“addition of a method step in a product claim, which product is not
patentably distinguishable from the prior art, cannot impart patentability to
the old product.” In re Dilnot, 300 F.2d 945, 950 (CCPA 1962).
In the absence of evidence showing that a tissue system that is formed
from reconstituted human extracellular matrix with an “artificial” or
“predefined” vascular network “formed from omnidirectional printing”
differs from natural human tissue, we decline to interpret these terms as
imposing any structural limitations that differentiate the tissue systems of
claims 1 and 29 from natural human tissue. Indeed, it is unclear how
“artificial” or “predefined” would distinguish from any product with a three-
dimensional vascular network because these terms do not impose any
structural limitations on the network. As to the “omnidirectional printing”
limitation, no evidence of record establishes any structural difference
imposed by this limitation.
Fronheiser teaches a tissue system composed of the ulnar and radial
arteries in the region of the wrist (FF 11). Fronheiser teaches that this tissue
comprises a plurality of channels (FF 12) that is physiologically relevant as a
network of vascular channels composed of the vascular network observed in
human physiology in vivo (FF 13).
Histology Guide evidences that natural human extracellular matrix is
optically transparent (FF 14) as required by claim 1.
Kloc evidences that the natural human vessels in Fronheiser are
composed of a multilayer coaxial structure with an interior cavity
comprising endothelial cells surrounded by a second layer comprising
smooth muscle cells that is itself surrounded by a third layer comprising
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fibroblast cells (FF 15).
Therefore, consistent with the analysis and evidence presented above,
Fronheiser anticipates a tissue system composed of optically transparent
human extracellular matrix supporting a physiologically relevant vascular
network that is in a three dimensional pattern as required by claim 1 (FF 11–
15). Fronheiser further anticipates a tissue system with a physiologically
relevant multi-channel vascular network in a three dimensional pattern that
forms the coaxial structure required by claim 29 (FF 11–15).
We note that “[w]hen the claimed compositions are not novel they are
not rendered patentable by recitation of properties, whether or not these
properties are shown or suggested in the prior art.” In re Spada, 911 F.2d
705, 709 (Fed. Cir. 1990). The burden to demonstrate that Fronheiser differs
from the tissue systems of claims 1 and 29 is shifted to Appellant.11
Therefore, on the current record, Fronheiser as supported by the Histology
Guide and Kloc evidentiary references anticipates claims 1 and 29.

11 We wish to emphasize that while Appellant may request rehearing under
37 C.F.R. § 41.50(b)(1), that rehearing is limited to the current evidence of
record under 37 C.F.R. § 41.52(a)(1): “Evidence not previously relied upon,
pursuant to §§ 41.37 , 41.41 , or 41.47 are not permitted in the request for
rehearing except as permitted by paragraphs (a)(2) through (a)(4) of this
section.” We note that paragraphs (a)(2) to (a)(4) applies to new arguments,
not new evidence. New arguments stating with particularity the points
believed to have been misapprehended or overlooked regarding the new
rejection based on the record evidence are permitted by this section in a
rehearing but rehearing is not an opportunity to continue prosecution such as
by adding new evidence, which is Appellant’s alternative option under 37
C.F.R. § 41.50 (b)(2).
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35 U.S.C. § 101
The Alice Test
The Supreme Court has long interpreted 35 U.S.C. § 101 to include
implicit exceptions: “[l]aws of nature, natural phenomena, and abstract
ideas” are not patentable. See, e.g., Alice Corp. v. CLS Bank Int’l, 573 U.S.
208, 216 (2014).
In determining whether a claim falls within an excluded category, we
are guided by the Supreme Court’s two-step framework, described in Mayo
and Alice. Id. at 217–18 (citing Mayo Collaborative Servs. v. Prometheus
Labs., Inc., 566 U.S. 66, 75–77 (2012)). In accordance with that framework,
we first determine if there is a judicial exception. Although composition of
matter claims are generally eligible subject matter, claims that are directed
only to laws of nature and/or natural phenomena are directed to patent
ineligible concepts. Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d
1371, 1376 (Fed. Cir. 2015).
If the claim is “directed to” a judicial exception, we turn to the second
step of the Alice and Mayo framework, where “we must examine the
elements of the claim to determine whether it contains an ‘inventive
concept’ sufficient to ‘transform’ the claimed abstract idea into a patent
eligible application.” Alice, 573 U.S. at 221 (quotation marks omitted).
2019 Guidance
The United States Patent and Trademark Office published guidance
on the application of 35 U.S.C. § 101. USPTO’s 2019 Revised Patent
Subject Matter Eligibility Guidance (“Guidance”).12 Under the Guidance, in

12 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg.
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determining what concept the claim is “directed to,” we first look to whether
the claim recites:
(1) any judicial exceptions, including “[l]aws of nature,
natural phenomena, and abstract ideas,” (quoting Alice, 573
U.S. at 216) and/or including certain groupings of abstract ideas
(i.e., mathematical concepts, certain methods of organizing
human activity such as a fundamental economic practice, or
mental processes) (Guidance Step 2A, Prong 1); and
(2) additional elements that integrate the judicial
exception into a practical application (see MPEP § 2106.05(a)–
(c), (e)–(h)) (Guidance Step 2A, Prong 2).

Only if a claim (1) recites a judicial exception and (2) does not
integrate that exception into a practical application, do we then look to
whether the claim contains an “‘inventive concept’ sufficient to ‘transform’”
the claimed judicial exception into a patent-eligible application of the
judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82).
In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial
exception that are not “well-understood, routine and
conventional in the field” (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional
activities previously known to the industry, specified at a high level of
generality, to the judicial exception.

(Guidance Step 2B). See Guidance, 84 Fed. Reg. at 54–56.
Analysis
A. Guidance Step 1

50–57 (January 7, 2019).
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We first consider whether the claimed subject matter falls within the
four statutory categories set forth in § 101, namely “[p]rocess, machine,
manufacture, or composition of matter.” Guidance 53–54; see 35 U.S.C.
§ 101. Claims 1 and 29 recite a “tissue system” and, thus, fall squarely
within the “composition of matter” category. Consequently, we proceed to
the next steps of the analysis.
B. Guidance Step 2A, Prong 1
The Revised Guidance instructs us first to determine whether any
judicial exception to patent eligibility is recited in claims 1 and 29. The
Revised Guidance identifies products of nature as having been identified by
the courts as judicial exceptions. 84 Fed. Reg. at 54. We therefore first look
to see if the claims recite any judicial exceptions.
As discussed in the anticipation rejection above, the tissue systems of
claims 1 and 29 are identical to the tissue comprising the natural vessel
disclosed in Fronheiser. Therefore, these claims encompass naturally
occurring human tissue. In particular, relevant to claim 1, the naturally
occurring human tissue of Fronheiser includes a vascular network of blood
vessels composed of human extracellular matrix that is physiologically
relevant and arranged in a three-dimensional pattern. Similarly for claim 29,
the natural human tissue in Fronheiser is composed of an extracellular
matrix support material, a vascular network with a plurality of channels in a
three-dimensional pattern that is physiologically relevant in the recited
coaxial configuration.
In Myriad, the Supreme Court noted that “Myriad did not create
anything. To be sure, it found an important and useful gene, but separating
that gene from its surrounding genetic material is not an act of invention”
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Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 593
(2013). Here, claims 1 and 29 encompass a material that was not created.
In order to be patent eligible, a “nonnaturally occurring manufacture
or composition of matter” must possess “markedly different characteristics
from any found in nature.” Id. at 590−91 (citing Diamond v. Chakrabarty,
447 U.S. 303, 309 (1980)). We apply the same analysis to the tissue system
of claims 1 and 29. Because claims 1 and 29 use the open “comprising”
language, we conclude the claims encompass tissue systems in human
beings. And even if these claims were interpreted to be limited to tissue
systems isolated from human beings, they still encompass natural products.
As the MPEP notes,
The courts have emphasized that to show a marked difference, a
characteristic must be changed as compared to nature, and
cannot be an inherent or innate characteristic of the naturally
occurring counterpart or an incidental change in a characteristic
of the naturally occurring counterpart. Myriad, 569 U.S. at 580
[ ]. Thus, in order to be markedly different, applicant must
have caused the claimed product to possess at least one
characteristic that is different from that of the counterpart.
MPEP § 2106.04(c)(II)(C).
These facts are similar to those in Bhagat, where our reviewing court
found that “the Applicant has not shown that the claimed mixtures are a
‘transformation’ of the natural products, or that the claimed mixtures have
properties not possessed by these products in nature.” In re Bhagat, 726 F.
App’x 772, 779 (Fed. Cir. 2018) (non-precedential). Similarly here, claims
1 and 29 as interpreted above have not been shown to transform natural
products or to have properties not possessed by the natural products.
Indeed, the Specification prefers embodiments “characterized by
exhibiting substantially similar shear stress on fluid and/or particles
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(including cells, etc.) passing therethrough as vascular networks observed in
human physiology” (Spec. ¶ 40). The Specification explains that the
network has “a bifurcating structure, inter-vessel spacing similar to that
observed in corresponding systems in vivo” (Spec. ¶ 70).
Appellant has provided no evidence that there are markedly different
characteristics between the claimed product and the product in nature.
Therefore, we conclude a judicial exception to patent eligibility is recited in
claims 1 and 29.
Guidance Step 2A, Prong 2
Having determined that claims 1 and 29 are directed to a judicial
exception, the Revised Guidance directs us to next consider whether the
claims integrate the judicial exception into a practical application. Guidance
Step 2A, Prong 2. “[I]ntegration into a practical application” requires that
the claim recite an additional element or a combination of elements, that
when considered individually or in combination, “apply, rely on, or use the
judicial exception in a manner that imposes a meaningful limit on the
judicial exception, such that the claim is more than a drafting effort designed
to monopolize the judicial exception.” Guidance at 54.
The claims do not include “specific methods of treatment that employ
a natural law” or “specific treatment formulations that incorporate natural
products.” Cf. Nat. Alternatives Int'l, Inc. v. Creative Compounds, LLC, 918
F.3d 1338, 1348 (Fed. Cir. 2019) (“Although beta-alanine is a natural
product, the Product Claims are not directed to beta-alanine. A claim to a
manufacture or composition of matter made from a natural product is not
directed to the natural product where it has different characteristics and the
potential for significant utility.”)
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Claims 1 and 29 do not include additional elements integrating the
natural product into a practical application that distinguish from the natural
product. Accordingly, we find that the claims are directed to the judicial
exception.
Guidance Step 2B
Having determined that the judicial exception is not integrated into a
practical application, the Guidance requires us to evaluate the additional
elements individually and in combination to determine whether they provide
an inventive concept. We evaluate whether additional elements in the
claims recite “an ‘inventive concept’ – i.e., an element or combination of
elements that is ‘sufficient to ensure that the patent in practice amounts to
significantly more than a patent upon the [ineligible concept] itself.’”
Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1375 (Fed. Cir.
2015). Particularly, we evaluate whether the claims include specific
limitations that are not “well-understood, routine, conventional activity
previously engaged in by scientists who work in the field.” Mayo, 566 U.S.
at 79.
There is no evidence that either claim 1 or claim 29 includes
unconventional elements relating to the naturally occurring tissue
composition itself. All of Appellant’s arguments relate to the process of
making the system, not the system itself (see Appeal Br. 6–24).
Accordingly, the claims recite the natural product itself, and thus, do not
supply an inventive concept.
We therefore find claims 1 and 29 unpatentable under 35 U.S.C. §
101.

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SUMMARY
In summary, we reverse the rejection of claims 1–11, 21, 23–26, and
28 under 35 U.S.C. § 103(a) as obvious over Vacanti, Tibbitt, and Ferris.
We reverse the rejection of claims 27 and 29 under U.S.C. § 103(a) as
obvious over Vacanti, Ferris, and Alberts.
We reject claims 1 and 29 under 35 U.S.C. § 102(b) as anticipated by
Fronheiser as evidenced by Histology Guide and Kloc.
We reject claims 1 and 29 under 35 U.S.C. § 101 as directed to non-
statutory subject matter.
This decision contains new grounds of rejection pursuant to 37 C.F.R.
§ 41.50(b). Section 41.50(b) provides “[a] new ground of rejection pursuant
to this paragraph shall not be considered final for judicial review.” Section
41.50(b) also provides:
When the Board enters such a non-final decision, the
appellant, within two months from the date of the decision,
must exercise one of the following two options with respect to
the new ground of rejection to avoid termination of the appeal
as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the prosecution
will be remanded to the examiner. The new ground of rejection
is binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the
opinion of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the
claims, appellant may again appeal to the Board pursuant to this
subpart.
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
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and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.

Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure § 1214.01.
In summary:
Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed New Ground
1–11, 21,
23–26, 28
103(a) Vacanti, Ferris,
Tibbitt
1–11, 21,
23–26, 28

27, 29 103(a) Vacanti, Ferris,
Alberts
27, 29
1, 29 102(b) Fronheiser,
Histology
Guide, Kloc
1, 29
1, 29 101 Product of
Nature
1, 29
Overall
Outcome
2–11, 21,
23–28
1, 29

REVERSED; 37 C.F.R. § 41.50(b)