Slivka et al.v.Hedman

Board of Patent Appeals and Interferences

Nov 23, 2010

10102075 (B.P.A.I. Nov. 23, 2010)

BoxInterferences@uspto.gov Paper 134
Telephone: 571-272-4683 ENTERED: 23 November 2010

UNITED STATES PATENT AND TRADEMARK OFFICE
BOARD OF PATENT APPEALS AND INTERFERENCES

Patent Interference No. 105,653

UNIVERSITY OF SOUTHERN CALIFORNIA
and Ampac Biotechnology, Inc.
(10/230,671),
Junior Party,

v.

DEPUY SPINE, INC.
(6,812,211),
Senior Party.

Before: RICHARD E. SCHAFER, RICHARD TORCZON and SALLY G.
LANE, Administrative Patent Judges.

TORCZON, Administrative Patent Judge.

JUDGMENT
Bd.R. 127
on motions
Interference No. 105,653 Page 2

I. INTRODUCTION
In view of the decision on priority and remaining motions,1 this
interference is now ripe for judgment.
II. JUDGMENT
JUDGMENT is ENTERED AGAINST the junior party on priority for
count 3,2 the sole remaining count;3
JUDGMENT is also ENTERED AGAINST the junior party on
unpatentability for its claims 24-34;4
Claims 1-15 and 18-37 of the junior party's involved 10/230,671
application are FINALLY REFUSED;5
JUDGMENT is ENTERED AGAINST the senior party on
unpatentability for all of its involved claims;6 and
Claims 1-45 of the senior party's involved 6,812,211 patent are
CANCELED, 35 U.S.C. 135(a).7

A copy of this judgment will be entered in the administrative records
of the involved patent and the involved application.

1 Paper 134.
2 Paper 133.
3 Paper 83 at 2.
4 Paper 82.
5 35 U.S.C. 135(a).
6 Papers 82 and 133.
7 35 U.S.C. 135(a).
Interference No. 105,653 Page 3

cc:

Robert Berliner, BERLINER & ASSOCIATES, of Los Angeles, California, and
Steven Highlander, FULBRIGHT & JAWORSKI LLP, of Austin, Texas.

Barry E. Bretschneider, Peter J. Davis and Jonathan Bockman, MORRISON &
FOERSTER LLP, of McLean, Virginia.

BoxInterferences@uspto.gov Paper 133
Telephone: 571-272-4683 ENTERED: 23 November 2010

UNITED STATES PATENT AND TRADEMARK OFFICE
BOARD OF PATENT APPEALS AND INTERFERENCES

Patent Interference No. 105,653

UNIVERSITY OF SOUTHERN CALIFORNIA
and Ampac Biotechnology, Inc.
(10/230,671),
Junior Party,

v.

DEPUY SPINE, INC.
(6,812,211),
Senior Party.

Before: RICHARD E. SCHAFER, RICHARD TORCZON and SALLY G.
LANE, Administrative Patent Judges.

TORCZON, Administrative Patent Judge.

DECISION
Bd.R. 125
on motions

The motion of the junior party (University) for judgment on priority is
DENIED;
The University's motion for judgment on obviousness is GRANTED;
Interference No. 105,653 Page 2

The University's motion for designation of claims as not
corresponding to the count is DENIED; and
The University's motion to exclude is DISMISSED as moot.
The motion of the senior party (DePuy) for judgment on priority is
DISMISSED as moot.
OPINION
I. INTRODUCTION
In a redeclaration of this interference, a new count (count 3) was
adopted.1 Count 3 defines the scope of the admissible priority proofs2 as
"The method of 10/230,671 claim 24."3 Claim 24 defines the University's
invention as:4
A method of improving the resistance of an intervertebral
disc to mechanical degradation by treating in a living being the
intervertebral disc having a nucleus pulposus which is degraded
or subject to ongoing degradation, comprising the step of:
a) injecting a composition consisting essentially of a
crosslinking agent into the nucleus pulposus,
wherein the crosslinking agent is injected in an effective
amount to cause in-situ crosslinking of native proteins present
in the nucleus pulposus.

For this count, each party was accorded the benefit of the filing date of its
involved application and patent, respectively. Accordingly, the constructive

1 Paper 83.
2 Bd.R. 201, "Count".
3 Paper 83 at 2.
4 Paper 6 (Univ. Clean Claims) at 4.
Interference No. 105,653 Page 3

reduction to practice date for the University is 29 August 2002 and for
DePuy, 19 March 2002.5
II. UNIVERSITY PRIORITY MOTION
A. Overview
The University pleaded conception by 26 August 1999, with diligence
from 21 March 2001, leading to actual reduction to practice by 14 May
2001.6
The University argues for two actual reductions to practice, 12 March
and 14 May 2001, but acknowledges that it in view of its pleading the March
proofs can only be used to prove the May date alleged in its pleading.7
B. Actual reduction to practice
1. The March experiment
The University's named inventor, Thomas P. Hedman, declares that in
February and March 2001 he conducted tests with an assistant on whole calf
spine segments to investigate different methods of delivering a crosslinking
reagent to intervertebral disc tissues.8 The assistant, Dean M. Gray, offers
similar declaration testimony.9 Notes from a 5 March 2001 meeting offer a
protocol involving five specimens: a no treatment control and two
crosslinking reagents ("Vinox" and genipin) at two concentrations,
respectively. The notes indicate a need for approximately five calf spines.

5 Paper 83 at 2.
6 Paper 27 (Univ. Priority Stmt.) at 1.
7 Paper 99 (Univ. Mot. 9) at 22-23; Bd.R. 120(b); Winter v. Lebourg,
394 F.2d 575, 580 (CCPA 1968) (proofs before pleaded date treated as
proving the pleaded date).
8 Exh. 1172, ¶15.
9 Exh. 1173, ¶6.
Interference No. 105,653 Page 4

The protocol called for "Syringe injection of reagents into soft tissue [and]
Quantification of crosslinks."10
Dr. Hedman and Mr. Gray testify that Exhibit 1171 (detail, below) is a
photograph of a transected disc separately injected11 with genipin and Vinox
on 9 March 2001 and transected and photographed on 12 March 2001.12 The
blue discoloration reflects oxidized genipin crosslinking, while the light-
brown discoloration is said to indicate Vinox injection.13 According to these
declarants, the asymmetric discoloration indicates a lateral injection into the
center of the disc, followed by diffusion through the soft tissue.14 Dr.
Hedman and Mr. Gray testify that they "understand" the discoloration to
indicate actual crosslinking of collagen rather than just the presence of the
crosslinking reagents.15

10 Exh. 1169.
11 The parties dispute whether the injection was "into the nucleus pulposus".
12 Exh. 1172, ¶15; 1173, ¶6.
13 Exh. 1172, ¶16; 1173, ¶7; mat'l fact 62B (admitted for genipin); mat'l
fact 62C (denied for Vinox). The final version of the material facts cited
throughout this opinion appears as Appendix 2 of Paper 120 (Univ.
Reply 9).
14 Exh. 1172, ¶17; 1173, ¶8.
15 Exh. 1172, ¶18; 1173, ¶9.
Interference No. 105,653 Page 5

The University must demonstrate, with a preponderance of the
evidence,16 that Hedman performed a process that met all the limitations of
count 3 and that he determined that the process would work for its intended
purpose.17 The requirement that all elements of the count must be shown
might seem stringent.18 If a party believes a different set of limitations
would better define the eligible priority proofs, its remedy is to move to
change the count.19
The present count, count 3, expressly requires "treating in a living
being the intervertebral disc having a nucleus pulposus which is degraded or
subject to ongoing degradation". The count is based on the University's
claim 24, which uses identical language. Moreover, DePuy's claims require
"treating in a living being an intervertebral disc".20 The original count,
count 1, was the union of the University's claim 24 and DePuy's claim 1,21
and thus required treating a living being. The University unsuccessfully
moved for a substitute count 2,22 which required "treating in a living being".
The University does not provide evidence of treating a living being.

16 Yorkey v. Diab, 601 F.3d 1279, 1286-87 (Fed. Cir. 2010); Bd.R. 207(a)(2).
17 Yorkey, 601 F.3d at 1286.
18 Indeed, it has been relaxed when 35 U.S.C. 102(g) is applied to claims
rather than a count. Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d
1316, 1336 (Fed. Cir. 2001) (reducing analysis to "key limitations").
19 Bd.R. 121(a)(1)(i); Bd.R. 208(a)(2); Bd.R. 208(c)(2); cf. Barton v. Adang,
162 F.3d 1140, 1146 (Fed. Cir. 1998) (holding show cause order premature
before decision on motion to change count).
20 Paper 12 (DePuy Clean Claims), claim 1, from which the others depend.
21 Paper 1 at 3.
22 Paper 23 (Univ. Mot. 1) at 1.
Interference No. 105,653 Page 6

Treating a living being limits count 3 rather than simply stating an
intended use. Griffin v. Bertina23 is instructive since it too involved a
medical method. In Griffin, the count was directed to:
A method…for diagnosing an increased risk of
thrombosis…
wherein the presence of said point mutation…indicates
an increased risk of thrombosis….
Griffin argued that thrombosis diagnosis was merely an intended use, while
Bertina contended that it was a limitation. Both the board and the court
concluded that diagnosis was "the essence" of the invention.24
Griffin is distinguishable from the present case in that the count was
worded a "method…for diagnosing", which on its face could be read as an
intended use. The "wherein" clause was held to have foreclosed the
intended-use reading. In the present case, the plain language of the count
does not permit a broader intended-use reading:
A method of improving the resistance of an intervertebral
disc to mechanical degradation by treating in a living being the
intervertebral disc….
The use of "by" rather than "for" indicates that the treating is instrumental.
Without the treatment step, the method would not be accomplished.
Precedent confirms that if an element of the count is limiting, it must
be shown in the priority proof. In addition to Griffin, the DePuy notes Eaton
v. Evans.25 In Eaton, the priority proof used an oscilloscope as a proxy for
the sense amplifier required in the count. The court held that the board erred

23 285 F.3d 1029 (Fed. Cir. 2002).
24 Id. at 1033.
25 204 F.3d 1094, 1097 (Fed. Cir. 2000).
Interference No. 105,653 Page 7

in accepting such a proof as establishing priority for the count.26 The court
rebuffed the board's reading of Scott v. Finney27 as permitting such proxies,
noting that in Scott there had been no question that Scott's proof had shown
all the limitations of the count.
Scott involved an implantable medical device. The count did not
require actual patient use of the device. The priority proof included a
videotape showing the device being implanted in a patient, experimentally
operated by a surgeon, and then removed. The dispute in Scott centered on
whether the showing provided sufficient evidence that the device would be
useful to the patient as a prosthesis.28 The present count is distinguishable
since it is a method that expressly requires treating a living being rather than
a device with minimal limitations on its use. Thus, the University's proof
needed to show not whether testing demonstrated that the method would be
useful for treating a living being, but simply whether it treated a living
being.
Since the March experiment lacked a central limitation of the count, it
cannot demonstrate an actual reduction to practice.

26 Id. at 1097-98.
27 34 F.3d 1058 (Fed. Cir. 1994).
28 Id.; accord Taskett v. Dentlinger, 344 F.3d 1337, 1341 (Fed. Cir. 2003)
(affirming actual transaction not in count so not required for actual reduction
of device); cf. Wetmore v. Quick, 536 F.2d 937, 942 (CCPA 1976) (rejecting
known substitute material as showing actual reduction of device).
Interference No. 105,653 Page 8

2. The May experiment
The May experiment had a protocol similar to the March experiment
in a key detail. The written protocol describes "Specimen preparation" in
which:29
Calf spine lumbar motion segments are separated by cutting
adjacent vertebrae in the transverse plane. Muscle, tendon, and
miscellaneous soft tissue are removed. The posterior ligament,
which is integrated with the posterior annulus, is left intact.
The spinous and transverse processes are removed by cutting
the pedicles in the frontal plane. On the anterior and lateral
faces of the vertebral body, a band of periostium is removed to
allow for better adhesion of the urethane potting material to the
cortical bone. A band of periostium of 5 to 10 mm is left above
and below the disc endplates.
The protocol nowhere mentions treatment of a living being.30
Once again, the University's proofs lack a central limitation of the
count. Without evidence including that limitation, the University fails to
establish an actual reduction to practice.
C. Holding
The University has not provided proofs of an actual reduction to
practice of the invention defined in count 3. Since the University's priority
case rests on proving an actual reduction to practice, the University has
failed to establish a facial case of priority.

29 Exh. 1161 at 1.
30 Id.
Interference No. 105,653 Page 9

III. DEPUY PRIORITY MOTION
The University has not established priority to a date before DePuy's
accorded benefit date. Thus, DePuy's motion31 to establish an even earlier
priority date is moot. The priority motion is accordingly dismissed as moot.
IV. UNIVERSITY MOTION TO EXCLUDE
The University moves to excluded DePuy exhibits 2082-2085.32
DePuy relied on these exhibits in its priority motion.33 DePuy does not
appear to have relied on these exhibits for in its oppositions to the
University's pending substantive motions.34 Since the only motion for which
the contested exhibits were cited has been dismissed as moot, this motion to
exclude them is similarly moot and thus is dismissed.
V. UNIVERSITY MOTION TO REDESIGNATE CLAIMS
A. Introduction
The University moves to have its claims 6, 8, 15 and 23 designated as
not corresponding to the count.35 Since the University has lost the contest
on priority, the question of whether these claims correspond to the count is
now ripe: it determines whether these claims are also lost in view of the
priority determination.36
A claim-correspondence analysis starts with the assumption that the
subject matter of the count is prior art to the movant. Based on this

31 Paper 106 (DePuy Mot. 5).
32 Paper 125 at (Univ. Misc. Mot. 10) at 1.
33 Paper 106 at 13 (Exh. List).
34 Paper 114 (DePuy Opp. 9) at 24-25 (Exh. List); Paper 115 (DePuy Opp. 7)
at 9 (Exh. List); Paper 116 (DePuy Opp. 8) at 16 (Exh. List).
35 Paper 97 (Univ. Mot. 7) at 1.
36 Bd.R. 207(b)(1) (for priority, corresponding claims stand or fall together).
Interference No. 105,653 Page 10

assumption the question is whether the subject matter of the contested claim
would have been anticipated or obvious over the prior art, including the
count.37 The rationale is that a patentably indistinct claim would be
estopped by the priority decision anyway.38 Conventional tests (anticipation
and obviousness) are used to determine patentable indistinctness now that
obviousness is accepted as applying to priority-anticipation.39 As the
movant, the University has the burden of proof for the relief it seeks.40
B. Claim 6
Claim 6 depends from claim 4, which depends from independent
claim 1.41 Claim 6 further limits the method of claim 4:
wherein the crosslinking agent is genipin, the carrier medium is
a buffered saline solution, and a concentration of the genipin in
the buffered saline solution is greater than 0.033%.
Despite the use of "a" to introduce the genipin concentration, there is no
apparent basis for more than one genipin concentration in the buffered saline
solution.
The University argues that the use of genipin as the crosslinking agent
is a patentable distinction. To support this argument, the University notes

37 Bd.R. 207(b)(1).
38 E.g., In re Deckler, 977 F.2d 1449, 1452 (Fed. Cir. 1992) (losing party not
entitled to claim patentably indistinct from count); In re Kyrides, 159 F.2d
1019, 1021-22 (CCPA 1947) (losing party not entitled to claim broader than
count).
39 35 U.S.C. 103(c) (specifically citing 35 U.S.C. 102(g) in an exception).
40 Bd.R. 121(b); Kubota v. Shibuya, 999 F.2d 517, 519 (Fed. Cir. 1993).
41 Paper 6 at 2. While these claims do not require treating a living being,
claim 1 requires "contacting…collagenous tissue within a human body".
Interference No. 105,653 Page 11

that DePuy's involved patent42 and a patent to Aksan43 use glutaraldehyde
rather than genipin as the crosslinking agent.44 The University also provides
the testimony of Jeffrey C. Lotz.45
Dr. Lotz is a member of the faculty at several California schools,
including the University of California at San Francisco.46 He has a doctorate
in medical engineering and a curriculum vitæ that shows an extensive
background in skeletal and spinal research.47 Dr. Lotz testifies that prior to
Dr. Hedman's work,
no one had shown, and one skilled in the art in this field would
not have expected, genipin crosslinking of intervertebral disc
tissue to have a beneficial effect with regard to disc
degradation.
Dr. Lotz does not provide a basis for this opinion other than his experience.
This testimony does not take into account the teachings of a paper by
Sung et al. cited in the University's written disclosure. The University's
involved application explains in the section entitled "Description of the
Related Art" that:48

42 Exh. 1003: M.A. Slivka & H. Serhan, Method for nonsurgical treatment of
the intervertebral disc and kit therefor, US 6,812,211 B2 (issued 2 Nov.
2004).
43 Exh. 2015: A. Aksan & J.J. McGrath, Method for controlling the chemical
and heat induced responses of collagenous materials, US 6,375,672 B1
(issued 23 April 2002).
44 Paper 97 at 3.
45 Exh. 1175: 2d Lotz declaration.
46 Id. at 7.
47 Id. at 7-16.
48 Exh. 1001: T.P. Hedman, Use of non-toxic crosslinking reagents to
improve fatigue resistance and reduce mechanical degradation of
Interference No. 105,653 Page 12

Sung (1999) found that a naturally occurring cross linking
agent, genipin, provided greater ultimate tensile strength and
toughness when compared with other crosslinking reagents.
Genipin also demonstrated significantly less cytotoxicity
compared to other more commonly used crosslinking agents.
However it also stood out in a negative sense with regard to
eliminating tissue anisotropy in bovine pericardium.
The other crosslinking reagents in the Sung article49 are gluteraldehyde, an
epoxy, and genipin.50 Sung used fresh bovine pericardia as collagen media
for crosslinking studies.51 Sung's findings are consistent with the
University's description, but it is worth noting that eliminating tissue
anisotropy may occur with all three agents, though more so with genipin.52
Sung concluded that the three agents:53
may produce distinct crosslinking structures. The differences in
crosslinking structure may affect crosslinking characteristics
and mechanical properties of the fixed tissue.
In short, Sung states that the different materials produce different results.
Sung does not, however, rule out the use of any of these three agents for
crosslinking collagen. When and whether to trade off tissue anisotropy for
significantly less cytotoxicity and greater tensile strength and toughness was
left to the reader. In a patient, significantly less cytotoxicity would likely be

intervertebral disc and other collagenous tissues, U.S. Appl'n 10/230,671
at 2-3 (filed 29 August 2002).
49 Exh. 2068: H.-W. Sung et al., Crosslinking characteristics and
mechanical properties of a bovine pericardium fixed with a naturally
occurring crosslinking agent, 47 J. Biomed. Materials Research, 116 (1999).
50 Id.
51 Id. at 118.
52 Id. at 124. Tissue anisotropy refers to differences in mechanical properties
in different dimensions (horizontal versus vertical).
53 Id. at 125.
Interference No. 105,653 Page 13

a very important factor. The University's disclosure does not explain how to
avoid elimination of tissue anisotropy when using genipin.
The Sung paper suggests the substitution of genipin for the more toxic
gluteraldehyde of the prior art, at least for uses in living beings. The
testimony of Dr. Lotz is entitled to little weight because it does not address
highly relevant prior art teachings known to the University.
The University has not demonstrated that claim 6 is patentably distinct
from the count.
C. Claim 8
1. Articular cartilage
Claim 8 depends from claim 1 and limits the collagenous tissue being
improved to "articular cartilage".54 Articular cartilage is cartilage that covers
the articular or joint surfaces of bones.55 The University notes that count 3
does not expressly address articular cartilage. Furthermore, the University
states that it is not aware of prior art that would suggest treating articular
cartilage with a crosslinking agent.
The University notes that DePuy's disclosure addresses treating
vertebral endplates and describes the endplates as being "a thin layer of
hyaline cartilage similar to articular cartilage."56 DePuy does not describe
treating articular cartilage, however. DePuy's disclosure is not prior art so it
is relevant mainly as evidence that vertebral endplate tissue is similar to
articular cartilage.

54 Paper 6 at 2.
55 Paper 122 (Univ. Reply 7) at 16, Mat'l Fact 6 (admitted).
56 Paper 97 at 4, citing Exh. 1003 at 4:24-29 and 5:24-26.
Interference No. 105,653 Page 14

2. Conditions within physiological limits to prevent
tissue overheating
The University also notes that the Aksan patent teaches the use of
crosslinking agents to treat joint injuries.57 The University argues that the
Aksan patent teaches away from its claimed method because Aksan requires
a heat treatment while claim 1, from which claim 8 ultimately depends,
requires "conditions within physiological limits to prevent tissue
overheating".58 DePuy counters that it is the combination of the subject
matter with the entire teaching of the Aksan patent that must be considered,
not simply Aksan's improvement viewed in isolation.59
Aksan teaches the use of both crosslinking and heat, either
simultaneously or heating first, then crosslinking. Heating and crosslinking
provide different advantages. Heating denatures the native collagen, causing
it to contract. Crosslinking stabilizes collagen, in this case in its contracted
form.60 Aksan distinguishes the prior art for not previously combining these
two known approaches to collagen modification.61 While Aksan teaches that
the combination of heat and crosslinking is an improvement over the prior
art, touting an improvement alone does not teach away from the separate
prior art processes. Teaching away requires active discouragement.62
Rather than teaching away, we find that Aksan teaches that crosslinking

57 Paper 97 at 4, citing Exh. 2015 at 3:52-54 and 4:12-13 and 23-29.
58 Paper 97 at 4.
59 Paper 115 at 2-3.
60 Exh. 2015 at 3:55-4:33.
61 Id. at 3:50-53.
62 DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327
(Fed. Cir. 2009), citing In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Interference No. 105,653 Page 15

would be expected to stabilize joint collagen albeit without the benefit of
first shrinking the tissue.63
D. Claims 15 and 23
The University treats claims 15 and 23 together.64 Claim 15 adds to
claim 1 "the step of[] periodically re-contacting the portion of the
collagenous tissue with an effective amount of a crosslinking reagent."65
Claim 23 adds to claim 1 "the step of[] periodically re-contacting the portion
of the collagenous tissue with an effective amount of the crosslinking
reagent."66 The University argues that the step of recontacting with the same
(or a different) crosslinking reagent is a patentable difference. The
University notes that DePuy teaches injecting the crosslinker at two different
sites rather than at the same site. The University also relies on the testimony
of Dr. Lotz.67
As noted above, DePuy's involved patent is not prior art for purposes
of this determination. In any case, our reading of DePuy's patent is that it
does not expressly include or exclude reapplication of the crosslinker to the
same site of the collagenous tissue. Moreover, the University's argument
begs the question what "portion" means in the claims, particularly whether a

63 Since articular cartilage is a joint-surface covering, it is not clear how
much benefit would come from shrinking the tissue first. The record is
silent on this point, so we have no basis for determining whether prior
shrinkage of articular cartilage would be more than simply an alternative for
the purposes of a teaching-away analysis.
64 Paper 97 at 4; In re Van Geuns, 988 F.2d 1181, 1186 (Fed. Cir. 1993)
(permitting claim grouping for patentability when they are not argued
separately).
65 Paper 6 at 3 (emphasis added).
66 Id. at 3 (emphasis added).
Interference No. 105,653 Page 16

portion may have multiple "sites". The University has not identified a
limiting definition for "portion". The closest the University came to
defining "portion" is that it is "the portion of the tissue that is subject to
loading" and, where the tissue is degraded, "the portion of the tissue that has
been degraded." The disclosure says that preferably the entire loaded or
degraded portion is contacted. "[T]issue adjacent [to] the portion of
collagenous tissue subject to the loading may also be contacted". In an
intervertebral disc, the "portion" is preferably two sites, "the posterior and
posterolateral annulus fibrosis." The disclosure further explains that
"[p]referably, the contact between the tissue and the crosslinking reagent is
effected by injections from a single or minimum number of injection
locations" and that "[p]referably, a sufficient number of injections are made
along the portion of the tissue to be treated so that complete coverage of the
portion of the collagenous tissue to be treated is achieved."68 The broadest
reasonable construction of "portion" consistent with the University's
specification is that "portion" means loaded or degraded collagenous tissue,
which may include multiple injection sites, but does not include adjacent
tissues. The more important difference is the claim language requiring
contacting "periodically", which would exclude multiple, but nearly
simultaneous, injections.
Dr. Lotz testifies that those skilled in the art would expect the
crosslinks to endure, which—69

67 Paper 97 at 5.
68 Exh. 1001 at 8-10.
69 Exh. 1175, ¶9.
Interference No. 105,653 Page 17

would obviate the need for a subsequent injection of a
crosslinking agent, certainly not more than one and most
certainly not a periodic re-contacting with [a] crosslinking
agent.
DePuy notes that Dr. Lotz provides no basis for this testimony.70 Indeed, the
testimony contradicts the University's disclosure, which explains:71
the methods and compositions treated herein are not required to
permanently improve the resistance of collagenous tissues in
the human body to mechanical degradation. Assuming that a
person experiences 2 to 20 upright, forward flexion bends per
day, the increased resistance to fatigue associated with contact
of the collagenous tissue with the crosslinking reagent, may,
over the course of time, decrease. Preferably, however, the
increased resistance to fatigue lasts for a period of several
months to several years without physiologic mechanical
degradation. Under such circumstance, the described treatment
can be repeated at the time periods sufficient to maintain an
increased resistance to fatigue resistance. Using the assumption
identified above, the contacting may be repeated periodically to
maintain the increased resistance to fatigue. For some
treatment, the time between contacting is estimated to
correspond to approximately 1 year for some individuals.
The disclosure presents its assumptions as logical inferences based on what
was known about the tissues to be treated, which suggests, if anything, that a
need for retreatment would have been expected, at least in some patients.
The Aksan patent is consistent with the University's disclosure: even
with the additional heat step, the invention "minimizes or substantially
abrogates the relaxation over time of the contracted collagen fibers".72

70 Paper 115 at 7.
71 Exh. 1001 at 10-11.
72 Exh. 2015 at 9:39-42.
Interference No. 105,653 Page 18

Indeed, in its discussion of skin treatments, Aksan expressly addresses
subsequent treatments according to its invention.73
We find Dr. Lotz's testimony is entitled to little or no weight since it
fails to identify underlying facts or data that supports his opinion74 and fails
to address evidence known to the University, including its own specification,
which appear to contradict his testimony.75 Alternatively, we find more
persuasive support in the University's specification and in Aksan that the
level of skill in the art at the time of the University's invention included an
expectation that treatment would not be permanent for all tissues in all
patients. This expectation would have lead to further maintenance treatment
as needed.
E. Holding
The University's claims 6, 8, 15 and 23 are not separately patentable
from the subject matter of the count.
VI. UNIVERSITY UNPATENTABILITY MOTION
A. Introduction
The University moves for judgment of unpatentability against DePuy
involved claims 34-37, 39-41 and 43-45.76 When the interference was
declared, all of DePuy's claims (1-45) were designated as corresponding to
the sole count.77 In a subsequent decision on motions, DePuy claims 1-33,

73 Id. at 12:1-2.
74 Bd.R. 158(a).
75 PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1360,
1361-62 (Fed. Cir. 2007) (crediting party's specification over its expert
testimony).
76 Paper 98 (Univ. Mot. 8) at 1.
77 Paper 1 at 3.
Interference No. 105,653 Page 19

38 and 42 were held to be unpatentable under 35 U.S.C. 103 (obvious to
those in the art). The remaining claims 34-37, 39-41 and 43-45 survived a
challenge under 35 U.S.C. 102 (anticipation), but were not challenged as
having been obvious.78 Since this disposition left lingering questions about
the patentability of DePuy's remaining claims, the University was authorized
to brief the obviousness of the remaining claims, but was substantially
limited to the then-existing record.79 DePuy argues each remaining claim
separately.80
B. Claim 34
Claim 34 incorporates the limitations of claim 1. Together they define
the invention as:81
1. A method of treating in a living being an intervertebral
disc having a nucleus pulposus, comprising the step of:
a) injecting a composition consisting essentially of a
crosslinking agent into the nucleus pulposus,
wherein the crosslinking agent is injected in an effective
amount to cause in-situ crosslinking of native proteins present
in the nucleus pulposus[,
34] wherein the native proteins are untreated.
The combined claims present a construction challenge because
claim 1 requires treatment of native proteins that claim 34 requires be
untreated. The University proceeds from the assumption that "untreated"

78 Paper 82 at 23-35.
79 Paper 92.
80 Paper 116 (DePuy Opp. 8) at 4-15.
81 Paper 12 at 3 & 5.
Interference No. 105,653 Page 20

means there is no prior treatment.82 For purposes of this motion, we shall
construe "untreated" to mean "un-pre-treated".
The law of the case83 holds that claim 1 would have been obvious
from the combined teachings and suggestions of a public presentation by
Thomas Hedman on 11 February 200284 and a patent to Froning.85 The
University reasons that the negative limitation "untreated" is met since the
Hedman presentation did not show pretreatment of the collagenous tissue.86
DePuy counters that claim 1 is not prior art and that the "untreated"
language distinguishes art such as the Aksan patent, where the collagenous
tissue may be treated with heat either prior to or simultaneously with the
crosslinking treatment.87 Claim 1 is not prior art, but we understand the
University to be using claim 1 as a summary for the prior art over which the
subject matter of claim 1 was held to have been obvious. While it is possible
to imagine scenarios where obviousness of an independent claim has little
bearing on a dependent claim,88 the relationship between DePuy's claim 1
and its dependent claims is sufficiently close that this concern is moot.

82 Paper 98 at 5:16-17.
83 Paper 82 at 31-33.
84 See Exh. 1031.
85 E.C. Froning, Apparatus and method for stereotaxic lateral extradural
disc puncture, U.S. Pat. 3,941,127 (granted 2 March 1976).
86 Paper 98 at 5:14-18
87 Paper 116 at 4-5.
88 For example, claim A includes a selection from a group of X or Y. The X
alternative is obvious, but the Y alternative is not. Dependent claim B
further limits claim A to the Y alternative.
Interference No. 105,653 Page 21

Precedent makes clear that a negative limitation can be met by a
simple absence of the excluded element in the prior art.89 Silence creates a
rebuttable presumption that the reference does not include the excluded
element. DePuy does not contend, and we find no basis for a contention,
that the Hedman presentation includes pretreatment of collagenous tissue.
Instead, DePuy relies on the Aksan patent to suggest inherent pretreatment.90
As previously discussed, Aksan claims as an improvement the
combined use of both heat and crosslinking treatments. Aksan does not,
however, teach away the use of crosslinkers alone.91 In providing
background for its invention, Aksan discusses the use of crosslinkers.92 In
context, this background must exclude Aksan's improvement of combining
crosslinking with heating. As with the Hedman presentation, there is no
indication of a need for any other pretreatment.
We find it to be more likely than not that a person having ordinary
skill in the art would have understood the references to at least suggest
treatment without pretreatment.

89 Süd-Chemie Inc. v. Multisorb Technologies Inc., 554 F.3d 1001, 1004-05
(Fed. Cir. 2009): "Moreover, Süd-Chemie has not offered any evidence that
a reference to a microporous or laminate film would be understood by one of
skill in the art as contemplating a film with an adhesive coating attached.
The district court was thus correct to characterize Komatsu as teaching the
use of uncoated films and not to interpret Komatsu as disclosing only films
coated with adhesives."
90 Paper 116 at 4-5.
91 Supra at V.C.2.
92 Exh. 2015 at 3:7-53.
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C. Claim 35
Claim 35 incorporates the limitations of claim 1 and adds the
limitation "wherein the native proteins are unmodified native proteins."93
Again, for the purposes of this opinion, we construe the limitation to be a
negative reference to pretreatment of the proteins. The parties' arguments
are largely the same. Again, while the Hedman presentation is silent
regarding prior modification, the simplest understanding of its teachings and
suggestions is that no prior modification is needed. Again, Aksan's
improvement involves prior or simultaneous modification of the native
proteins, it stands in contrast to methods discuss in Aksan's background,
which do not appear to have modified the native proteins.
We find it to be more likely than not that a person having ordinary
skill in the art would have understood the references to at least suggest
treatment without prior modification of the treated proteins.
D. Claims 36 and 37
Claim 36 incorporates the limitations of claim 1 and adds the
limitation "wherein the injection produces a therapeutic effect of relieving
pressure on a neural element." Claim 37 incorporates the limitations of
claim 36 and adds "wherein the neural element is a spinal cord."94 The
University notes that the Hedman presentation addressed reducing
mechanical degradation of intervertebral discs and argues that treating
related pain is inherent. Similarly, the University notes the proximity of the
spinal cord to intervertebral discs.95

93 Paper 12 at 3 & 5.
94 Paper 12 at 3 & 5.
95 Paper 98 at 6.
Interference No. 105,653 Page 23

DePuy argues that a portion of the presentation on which the
University relies is uncorroborated hearsay. DePuy also notes the absence
of evidence supporting the University's inherency arguments.96 The
University replies with the argument that statements of results for process
steps are not limiting.97
The earlier decision held that it was the presentation, not the slides,
that was the prior art. It proceeded to corroborating testimony that
specifically mentioned certain slides as evidence of the content of the
presentation. The University relies on slides 18 and 25. Slide 18 was not
part of the corroborating testimony, but slide 25 was. Slide 25 provides
three bullets:
Non-toxic crosslinking reagents proving effective in reducing
fatigue-induced degradation
Tests w/human discs, elastic degradation testing underway
Early results suggest treatment may reduce mechanical disc
degradation.
The University's claim construction argument appears to be new in the
reply and thus prejudicial to DePuy.98 In any case, there is no such
categorical rule for results statements in claims. The University relies on
Minton v. National Association of Securities Dealers, Inc.,99 in which the
court specifically addressed a "whereby" clause rather than results language

96 Paper 116 at 7-9.
97 Paper 121 at 2, 5 & 6.
98 Bd.R. 122(b).
99 336 F.3d 1373 (Fed. Cir. 2003).
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generally. Moreover, even whereby clauses must be evaluated on the
specific facts of the case.100
DePuy is right that the University's motion is long on attorney
argument and short on evidence. Nevertheless, there is a role for common
sense in patent law.101 Most adults would understand that pain is a key
symptom of intervertebral disc degeneration and a central reason its
sufferers seek treatment. Thus, the connection between a degenerating disc
and pressure on some neural element is readily apparent.
The background section of DePuy's own disclosure indicates that the
spinal cord is often affected when the disc degenerates. There is no
indication that DePuy's inventors were the origin of this knowledge.102
Hence, we attribute this knowledge to the pre-existing skill in the art. It
follows that in a patient whose disc degeneration is affecting the spinal cord,
a person having ordinary skill in the art would expect treatment producing a
therapeutic effect for the disc to relieve pressure on the spinal cord.
A preponderance of the evidence suggests that a person having
ordinary skill in the art would have considered the subject matter of claim 36
and 37 to be obvious.
E. Claims 39, 40 and 41
Claim 39 incorporates the limitations of claim 1 and adds the
limitation "wherein the injection substantially prevents prolapse of a portion
of the nucleus pulposus." Claim 40 incorporates the limitations of claim 39

100 Griffin v. Bertina, 285 F.3d 1029, 1034 (Fed. Cir. 2002) (distinguishing
whereby cases from the "wherein" clause under review).
101 KSR Int'l v. Teleflex Inc., 550 U.S. 398, 420-21 (2007).
102 Exh. 1003 at 1:20-28.
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and adds "wherein the substantial prevention of prolapse of the portion of
the nucleus pulposus sustains disc height." Claim 41 incorporates the
limitations of claim 39 and adds "wherein the substantial prevention of
prolapse prevents leakage of material of the nucleus pulposus from the disc
into a neural foramen."103
The University argues that the therapeutic effect of injecting the
crosslinking composition would be substantial prevention of prolapse.
Moreover, preventing prolapse would inherently sustain disc height and
prevent leakage.104 DePuy responds that the University presents no evidence
and that none of these effects would necessarily follow since they would
depend on location and dosage.105
Again, while the evidence on both sides is sparse, the relevant
question is what one skilled in the art would have understood from the
Hedman presentation and the Froning patent. In our earlier decision, we
found that Hedman taught treating the nucleus pulposus with a crosslinking
agent.106 We also found it likely that those skilled in the art would have
expected diffusion of the therapeutic agent in the disc beyond to point of
injection.107 Since the point of crosslinking is to make the native collagen
more rigid, it is reasonable to infer that it would reduce prolapse, which in
turn would maintain disc height and prevent leakage of the crosslinked
tissue. While DePuy's point about dose and injection site seems legitimate,
the claims are not precise about either of these requirements. In any case,

103 Paper 12 at 3 & 5-6.
104 Paper 98 at 6-7.
105 Paper 116 at 9-10.
106 Paper 82 at 31, finding 25.
107 Id. at 35.
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we have no direct evidence about the ability or inability of those skilled in
the art to determine dosage and injection location. The Froning patent,
however, is directed to precision of injection.108 Moreover, the attendees at
the Hedman presentation appeared to apprehend immediately the clinical
possibilities of injecting crosslinking agents.109 In sum, the best inference
from the available evidence is that those skilled in the art would have been
motivated from the Hedman presentation to inject crosslinking agents to
achieve precisely the benefits listed in claims 39-41.
F. Claim 43
Claim 43 incorporates the limitations of claim 1 and adds the
limitation "wherein the disc further has an annulus fibrosus, and both the
nucleus pulposus and the annulus fibrosus are treated with the same injection
of crosslinking agent."110 The University argues that the Hedman
presentation taught treatment of both the nucleus pulposus and the annulus
fibrosus.111 DePuy responds that the presentation teaches soaking not
injection and that treatment would be dependent on injection site and
dosage.112
The soaking method of the Hedman presentation, if anything, supports
the idea that the injected composition would diffuse through the disc.
Certainly how much it diffused would depend on the injection site and
dosage (as well as other factors, like the pharmaceutical carrier used in the
injected composition with the crosslinker). As we explained for claim 39,

108 Id. at 32.
109 Id. at 31.
110 Paper 12 at 3 & 6.
111 Paper 98 at 7.
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however, claim 43 is not limited to a particular injection site or dosage and
the evidence such as it is suggests that a person having ordinary skill in the
art would have enough information to determine these factors through
existing knowledge and routine experimentation.
G. Claim 44
Claim 44 incorporates the limitations of claim 1 and adds the
limitation "wherein the injection causes crosslinking of substantially the
entire nucleus pulposus."113 The University argues that crosslinking
substantially all of the nucleus pulposus is inherent.114 DePuy again points
to the lack of evidence and denies the inevitability of crosslinking the entire
nucleus pulposus.115 DePuy's points are well taken. There is nothing
inherent about the entire nucleus pulposus being crosslinked from an
injection. On the other hand, a person having ordinary skill in the art would
have appreciated that the goals of preventing prolapse and leakage are better
met as more of the nucleus pulposus was crosslinked. It is more likely than
not that one skilled in the art would have selected the number, location, and
dosage of the injections to attain crosslinking of substantially all of the
nucleus pulposus.
H. Claim 45
Claim 45 incorporates the limitations of claim 44 and adds the
limitation:116

112 Paper 116 at 12
113 Paper 12 at 3 & 6.
114 Paper 98 at 7.
115 Paper 116 at 13.
116 Paper 12 at 3 & 6.
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wherein the nucleus pulposus has a periphery and the disc
further has an annulus fibrosus, the annulus fibrosus having an
inner wall, and wherein the injection further causes crosslinking
of the periphery of the nucleus pulposus to the inner wall of the
annulus fibrosus.
The first part of the added claim language describes the disc and is not
contested. The contest lies in the crosslinking of the nucleus pulposus to the
adjacent wall of the annulus fibrosus. The University argues that such
crosslinking is inherent.117 DePuy again disputes inherency. Here, however,
the inherency seems clear. If substantially all of the nucleus pulposus is
treated, then it would be exceptionally hard to avoid diffusion to the
periphery of the nucleus pulposus. The crosslinking agent cannot
distinguish between the collagen of the nucleus pulposus and the collagen of
the annulus fibrosus. Thus, without careful planning to avoid it (or
extraordinary luck), treatment of substantially all of the nucleus pulposus
will necessarily result in at least some crosslinking between adjacent
collagens in the nucleus pulposus and the annulus fibrosus.
I. Holding
The subject matter of claims 34-37, 39-41 and 43-45 would have been
obvious to a person having ordinary skill in the art.

117 Paper 98 at 8.
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cc:

Robert Berliner, BERLINER & ASSOCIATES, of Los Angeles, California, and
Steven Highlander, FULBRIGHT & JAWORSKI LLP, of Austin, Texas.

Barry E. Bretschneider, Peter J. Davis and Jonathan Bockman, MORRISON &
FOERSTER LLP, of McLean, Virginia.