LIFELINE SCIENTIFIC, INC.

Patent Trials and Appeals Board

Mar 11, 2020

14057521 - (D) (P.T.A.B. Mar. 11, 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.
14/057,521 10/18/2013 Kelvin G. M. BROCKBANK 154260 6686
27049 7590 03/11/2020
OLIFF PLC
P.O. BOX 320850
ALEXANDRIA, VA 22320-4850
EXAMINER
FAN, LYNN Y
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
03/11/2020 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):
OfficeAction27049@oliff.com
jarmstrong@oliff.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KELVIN G. M. BROCKBANK1
Appeal 2019-003724
Application 14/057,521
Technology Center 1600
Before ERIC B. GRIMES, DEBORAH KATZ, and
ULRIKE W. JENKS, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
biomaterial composition, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
The Specification states that “chondrocytes and cartilage tissue are
preserved using various storage techniques, and . . . used as osteochondral

1 Appellant identifies the real party in interest as LIFELINE SCIENTIFIC,
INC. Appeal Br. 1. We use the word Appellant to refer to “applicant” as
defined in 37 C.F.R. § 1.42(a).
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allografts.” Spec. ¶ 4. However, “[c]urrent preservation techniques do not
acceptably maintain extracellular matrix integrity of cartilage, and in certain
aspects, chondrocyte viability could be improved.” Id. ¶ 5.
The Specification discloses “compositions and methods for storing
biomaterials . . . in a manner that reduces or prevents the loss of biomaterial
properties, such as extracellular matrix permeability and chondrocyte
viability.” Id. ¶ 8. “In certain aspects, the solutions described herein contain
an agent that prevents or reduces the loss of biomaterial properties,” which
can be an enzyme inhibitor such as doxycycline. Id.
“After placing the biomaterial into any of the solutions . . . , this
mixture can be stored at various temperatures,” including hypothermic
temperatures. Id. ¶ 34. “In certain aspects, hypothermic temperatures can
include temperatures ranging -25°C from to +35°C. . . . For example, if
chondrocytes and/or cartilage are the biomaterial, hypothermic temperatures
rang[e] preferably from -25°C to +35°C.” Id.
Claims 1, 3–5, 7–10, and 22–31 are on appeal. Claim 1, reproduced
below, is illustrative:
1. A composition comprising a biomaterial and a solution that
includes at least one agent that reduces or prevents a loss of biomaterial
properties during storage of the biomaterial at hypothermic temperatures,
wherein
a temperature of the composition is a hypothermic temperature,
the solution is an animal product-free solution,
the biomaterial comprises chondrocytes in an extracellular matrix or
cartilage,
the at least one agent comprises doxycycline having a concentration of
10 μM, and
the biomaterial properties comprise:
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cell viability; and
extracellular matrix integrity, which includes extracellular
matrix permeability.

The claims stand rejected as follows:
Claims 1, 3–5, 7, 9, 22–25, 29, and 30 under 35 U.S.C. § 103(a) as
obvious based on Cole2 (Ans. 3);
Claims 8, 26–28, and 31 under 35 U.S.C. § 103(a) as obvious based
on Cole and Brockbank3 (Ans. 5); and
Claim 10 under 35 U.S.C. § 103(a) as obvious based on Cole and
Nagase4 (Ans. 6).
OPINION
Claims 1, 3–5, 7, 9, 22–25, 29, and 30 stand rejected as obvious based
on Cole. The Examiner finds that “Cole teaches a culture (a composition)
comprising tibias (a biomaterial comprises chondrocytes in an extracellular
matrix and cartilage . . . ) in serum-free media (an animal product-free
solution) . . . and 5 μg/ml (11.25 μM) of doxycycline.” Ans. 4.
The Examiner presents the calculations relied on for converting 5
µg/ml doxycycline to 11.25 µM. Id. at 8. The Examiner also notes that

2 Ada A. Cole, et al., Doxycycline Disrupts Chondrocyte Differentiation and
Inhibits Cartilage Matrix Degradation, Arthritis & Rheumatism 37:1727–
1734 (1994).
3 Kelvin G.M. Brockbank et al., Tissue Preservation, in Advances in
Biopreservation, pages 157–196 (2006).
4 Hideaki Nagase et al., Aggrecanases and cartilage matrix degradation,
Arthritis Res Ther. 5:94–103 (2003).
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Cole does teach a dosage of 10 μM doxycycline is used in the
study (p.1732 col right - para 1). Hence, Cole discloses a
composition comprising the claimed biomaterial and the
claimed solution including doxycycline, and the disclosed 10
μM of doxycycline of Cole would reduce or prevent a loss of
biomaterial properties . . . , since doxycycline of Cole appears
to be the same as claimed.
Id.
The Examiner notes that claim 1 recites a “hypothermic temperature,”
and some dependent claims recite specific temperature ranges, but considers
these “intended use limitations.” Id. at 4–5. The Examiner reasons that “[t]he
intended use of the claimed composition does not patentably distinguish the
composition, per se. . . In order to be limiting, the intended use must create a
structural difference between the claimed composition and the composition
of the prior art. In the instant case, the intended use fails to create a structural
difference.” Id. at 5.
We agree with the Examiner that claim 1 is unpatentable based on
Cole. Claim 1 is directed to a composition that comprises “a biomaterial”;
specifically, a biomaterial comprising “chondrocytes in an extracellular
matrix or cartilage.” Cole discloses cultures comprising “[t]ibias from 12-
day chick embryos.” Cole 1728, right col. “[A]t 12 days of embryonic
development . . . the tibia consists of a thin bony collar, a marrow cavity,
and 2 tibial cartilages.” Id. at 1727–1728.
Cole’s cultures also include “serum-free media containing Dulbecco’s
modified Eagle’s medium” supplemented with ascorbate, glucose, and
penicillin/streptavidin. Id. at 1728, right col. Cole’s serum-free medium
reasonably appears to be free of animal products. See Spec. ¶ 27 (Suitable
solutions include “Dulbecco’s Modified Eagle Medium”; animal product-
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free solutions do not contain “fetal bovine serum (FBS) or any other product
derived from an animal.”).
Cole states that “treated tibias were incubated in the presence of
doxycycline at 5 µg/ml, 20 µg/ml, or 40 µg/ml.” Cole 1728, right col. Cole
also states “[t]he dosage of doxycycline used in this study (83 μM, 41 μM,
and 10 μM) is comparable with the drug concentrations reported by other
investigators to inhibit enzyme activity of neutrophil collagenase but not
fibroblast collagenase.” Id. at 1732. This statement is reasonably interpreted
to be Cole’s conversion of the µg/ml units used in its experiments (“in this
study”) to units of µM, to make them directly comparable to the doxycycline
concentrations used “by other investigators” in their own studies. Thus,
Cole’s disclosure supports the Examiner’s finding (Ans. 8) that Cole’s
composition comprises 10 µM doxycycline.
Claim 1 recites an “agent that reduces or prevents a loss of biomaterial
properties during storage of the biomaterial at hypothermic temperatures,
wherein . . . the biomaterial properties comprise: cell viability; and
extracellular matrix integrity, which includes extracellular matrix
permeability.” Claim 1 also recites the agent that meets this functional
requirement: 10 µM doxycycline. Because Cole’s composition comprises
10 µM doxycycline, it would inherently possess the functional properties
that result from including 10 µM doxycycline in a composition. Cole’s
composition therefore meets the functional limitation recited in claim 1.
Finally, claim 1 states that “a temperature of the composition is a
hypothermic temperature.” Cole discloses that “[t]he tibias were maintained
in culture . . . at 37°C.” Cole 1728, right col. The Specification states that
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“hypothermic temperatures can include temperatures ranging -25°C from to
+35°C.” Spec. ¶ 34. This statement, however, does not purport to define the
term “hypothermic temperature,” nor does it limit hypothermic temperatures
to those between -25°C and +35°C; it only states that “hypothermic
temperatures can include” that range. Thus, the broadest reasonable
interpretation of “a hypothermic temperature,” read in light of the
Specification, includes some temperatures below -25°C and some
temperatures above +35°C, possibly including +37°C, the temperature of
Cole’s composition.
Even assuming that the broadest reasonable interpretation of “a
hypothermic temperature” does not include +37°C, however, we conclude
that the temperature limitation of claim 1 does not result in a structural
difference. Cole’s composition comprises the same biomaterial, the same
solution, and the same doxycycline concentration as the claimed
composition. Cole’s composition therefore appears to be identical to the
claimed composition, even though it might have a different temperature.
Where . . . the claimed and prior art products are identical or
substantially identical . . . the PTO can require an applicant to
prove that the prior art products do not necessarily or inherently
possess the characteristics of his claimed product. Whether the
rejection is based on “inherency” under 35 U.S.C. § 102, on
“prima facie obviousness” under 35 U.S.C. § 103, jointly or
alternatively, the burden of proof is the same, and its fairness is
evidenced by the PTO’s inability to manufacture products or to
obtain and compare prior art products.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (citations and footnote
omitted).
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Appellant has not provided evidence that a composition comprising
the components recited in claim 1, at a temperature of +37°C, differs from
an otherwise identical composition at a “hypothermic” temperature of
+35°C, or even that it differs from one at +5°C, as recited in some dependent
claims.
Appellant argues, however, that “even if . . . Cole can be interpreted
as teaching that a dosage of 10 μM doxycycline is used in Cole . . . , the
composition of Cole is not the same as the claimed composition.” Reply Br.
4. Specifically, Appellant argues that
the “structural difference” brought about by the expressly
recited . . . hypothermic temperature . . . is that—unlike
[Cole] in which [doxycycline] is used at 37°C where the
chondrocytes proliferate (i.e., the cartilage should grow) —the
hypothermic temperature requirement of the claims effectively
holds the recited biomaterial comprising chondrocytes in stasis
in the cold, i.e., there is no proliferation and/or even any
expectation of proliferation at the recited hypothermic
temperatures.
Id. at 4–5. Appellant thus argues that the recited hypothermic temperature
“creates a structural difference at least in terms of chondrocyte proliferation
in the composition.” Id. at 5.
This argument is unpersuasive. First, the Specification does not
describe “a hypothermic temperature” as one that “holds . . . chondrocytes in
stasis in the cold,” as Appellants argue. Reply Br. 5. The Specification
states, rather, that “hypothermic temperatures can include . . . +35°C,”
Spec. ¶ 34, which is equivalent to about 95°F.
In addition, we are not persuaded that the effect of the temperature of
a composition on its components (including living components such as
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chondrocytes) is a change in its structure. Neither the identity nor the
amounts of the components of Cole’s composition—Dulbecco’s modified
Eagle’s medium, animal product-free supplements, 10 µM doxycycline, and
embryonic chick tibias—change when the temperature of the composition is
lowered from 37°C to 35°C, or even to 5°C.
Rather, a change in the temperature of a composition affects its
functional properties by changing the rate of movement of the molecules
making up that composition, which affects the rate of chemical reactions,
including the chemical reactions taking place in living cells. Although cells
may grow more slowly, or not at all, in compositions that are colder,
Appellant does not direct us to evidence to support the argument that any
change is due to a change in the composition, rather than a change in the
environment in which the composition is placed, which determines its
temperature.
A similar issue was addressed in SmithKline Beecham Corp. v. Copley
Pharm., Inc., 45 Fed. Appx. 915 (Fed. Cir. 2002). The issue presented was
whether a prior art reference “anticipates claims 2 and 4 . . . directed to
nabumetone, an anti-inflammatory drug.” Id. at 916. “The only difference is
that claim 2 claims the chemical in its solid form, and claim 4 recites the
compound in an oil form.” Id. at 917. The court concluded that, “[b]ecause
expert testimony confirmed that nabumetone when made is in an oil form
and always solidifies at room temperature, . . . the solid form is an inherent
property of the compound. Thus claim 2 is inherently anticipated by” the
prior art. Id.
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Just as the compound in Copley did not change its structure when it
solidified at room temperature, Appellant’s claimed composition does not
change its structural make-up when its temperature is changed from 37°C to
35°C, or 5°C. Thus, whatever effect the claimed composition has on
chondrocytes at a given temperature is inherent in the composition, and
therefore also inherent in the structurally identical composition disclosed by
Cole.
In the Appeal Brief, Appellant argued that Cole’s teachings would not
have led a skilled artisan to modify its doxycycline concentration to the
claimed 10 µM. Appeal Br. 8–9, 11–12, 15. These arguments are
unpersuasive in view of Cole’s own conversion of its 5 µg/ml doxycycline
concentration to 10 µM. Cole 1728, right col. (“doxycycline at 5 µg/ml, 20
µg/ml, or 40 µg/ml”) and 1732, right col. (“[t]he dosage of doxycycline used
in this study (83 μM, 41 μM, and 10 μM)”). Thus, no modification of Cole’s
doxycycline concentration is required to meet the relevant claim limitation.
Appellant also argues that the claimed composition
results in superior properties. . . . [T]he electrical conductivity
data of Figure 6 (which takes into account the proteoglycan
content) reflects that 10 μM achieved the best results for
retention of electrical conductivity and permeability, in the
presence of viable cells (even regarding viability, as further
shown in Figure 5, the 10 μM group was significantly higher
than all other groups), which is not suggested by the results
described in Cole.
Appeal Br. 16. Appellant argues that
there is no evidence of record, suggesting that one skilled in the
art would have thought that the recited agent (including
doxycycline having a concentration of 10 μM) could or should
be effective to reduce or prevent the loss of the recited
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biomaterial properties (including cell viability and extracellular
matrix integrity, which includes extracellular matrix
permeability) at hypothermic temperatures (i.e., refrigeration
temperatures) where metabolism is very low.
Id. at 17.
These arguments are unpersuasive. The data shown in Appellant’s
Figures 5 and 6 compares samples having 0, 10, 30, 100, or 300 µM
doxycycline. Appellant argues that the 10 µM sample “achieved the best
results,” including “significantly higher” viability. Appeal Br. 16. However,
Cole’s composition also comprises 10 µM doxycycline. Cole 1728, right col.
Thus, whatever properties are conferred on the claimed composition based
on 10 µM doxycycline cannot be the basis for showing a difference, let
alone an unexpected difference, from Cole’s composition. Cf. Atlas Powder
Co. v. IRECO Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery
of a previously unappreciated property of a prior art composition . . . does
not render the old composition patentably new to the discoverer.”).
With regard to claim 22, Appellant argues that “[t]he record lacks any
articulation of a finding that the prior art included the features as recited in
claim 22, which requires the composition is without ice nucleation (at
hypothermic temperatures).” Appeal Br. 18.
We are not persuaded. Claim 22 reads: “The composition of claim 1,
wherein at the hypothermic temperatures the composition is without ice
nucleation.” Appeal Br. A-2. Claim 22 does not require any additional
components (e.g., an antifreeze agent) compared to claim 1, and any
composition is “without ice nucleation” when it is entirely liquid. Claim 22
therefore reads on the composition of claim 1 in a liquid condition; e.g., at a
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hypothermic temperature of 35°C or 5°C. Thus, claim 22 is unpatentable
over Cole for the reasons discussed above with respect to claim 1.
With regard to claims 29 and 30, Appellant argues:
Nowhere does Cole or the other applied references suggest a
hypothermic temperature composition including the claimed
ingredients, much less one in which the temperature of the
composition (including all the ingredients therein) is
specifically set in the range from -5°C to +10°C, or in the range
from -0°C to +5°C.
Appeal Br. 20.
This argument is also unpersuasive, for the reasons discussed above
with respect to claim 1. To reiterate, the temperature of a composition does
not change what the composition is made of; the temperature only changes
the rate at which molecules in the composition move. Appellant fails to
direct us to evidence showing that the identity and amount of the
components in Cole’s composition are the same at 5°C as they are at 37°C.
Thus, the temperature ranges recited in claims 29 and 30 do not structurally
distinguish the claimed compositions from Cole’s composition.
Appellant has waived arguments directed specifically to the rejections
based on Cole combined with Brockbank or Nagase. See Appeal Br. 5 (“For
the reasons detailed below, Appellant requests the reversal of the Examiner’s
rejections [collectively].”). For the reasons set out in the Answer and above,
therefore, we affirm the rejection of claims 8, 26–28, and 31 under 35 U.S.C.
§ 103(a) based on Cole and Brockbank, and the rejection of claim 10 under
35 U.S.C. § 103(a) based on Cole and Nagase.
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 3–5, 7, 9,
22–25, 29,
30
103(a) Cole 1, 3–5, 7, 9,
22–25, 29, 30

8, 26–28, 31 103(a) Cole, Brockbank 8, 26–28, 31
10 103(a) Cole, Nagase 10
Overall
Outcome
1, 3–5, 7–10,
22–31

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED