Schense, Jason et al.

Patent Trials and Appeals Board

Oct 22, 2019

13226618 - (D) (P.T.A.B. Oct. 22, 2019)

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.
13/226,618 09/07/2011 Jason Schense KUROS 142 3980
23579 7590 10/22/2019
Pabst Patent Group LLP
1545 PEACHTREE STREET NE
SUITE 320
ATLANTA, GA 30309
EXAMINER
BROWE, DAVID
ART UNIT PAPER NUMBER
1617
MAIL DATE DELIVERY MODE
10/22/2019 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JASON SCHENSE,
SILKE MARK, MONICA ALVISI,
and MARIA ANGELES MARTINEZ VARGAS
Appeal 2017-002307
Application 13/226,618
Technology Center 1600
Before JEFFREY N. FREDMAN, TAWEN CHANG, and DAVID COTTA,
Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1, 2, 4, 5, 9, 10, 27, and 28. We have
jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

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 Kuros
Biosurgery AG. Appeal Br. 2.
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BACKGROUND
Spinal fusion is “a surgical procedure aimed at achieving bone
formation and thereby fusion between two or more adjacent vertebrae.”
(Spec. 10:12–14.) The Specification states that in spinal fusion “[a] bone
graft is needed to create the appropriate environment in order for a solid
bone bridge to form between the vertebrae” and that currently “[a] variety of
materials . . . serve as bone grafts or bone graft substitutes, including
autografts . . ., allografts, demineralised bone matrix, and various synthetic
materials” such as “calcium phosphates or hydroxyapatites, stem cell
containing products . . ., and . . . growth factor containing matrices.” (Id. at
2:27–3:6.) According to the Specification, “[i]t is an object of the present
invention to provide a bone graft substitute which effectively fuses vertebrae
in spinal fusion procedures and is safer to use than the currently available
bone graft substitutes.” (Id. at 3:28–30.)
CLAIMED SUBJECT MATTER
The claims are directed to a spinal fusion method for treatment of a
human patient. Claim 1 is illustrative:
1. A spinal fusion method for treatment of a human
patient in need thereof, comprising
administering to the patient at a site between two
adjacent vertebrae in need of spinal fusion a pharmaceutical
composition capable of forming under physiological conditions
a bone graft substitute,
wherein the pharmaceutical composition comprises one
or more matrix forming materials and parathyroid hormone
(PTH), wherein the composition does not contain any additional
added peptide or protein bioactive factor with bone forming
properties,
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wherein during or after administration, the
pharmaceutical composition forms a bone graft substitute at the
site,
wherein the bone graft substitute comprises a matrix and
the PTH, and does not contain any additional added peptide or
protein bioactive factor with bone forming properties,
and
wherein the bone graft substitute locally delivers the PTH
to the site in an effective amount to achieve bone formation
between the vertebrae.
(Appeal Br. 31.)
The Examiner explains, and Appellant does not dispute, that
Appellant’s elected claims are directed to a spinal fusion
method for treatment of a human patient in need thereof
comprising administering to the patient at a site between two
adjacent vertebrae a composition comprising i) fibrinogen and
thrombin, as matrix precursor components, with a calcium
source, wherein the components interact with each other to
form a fibrin matrix during or after administration; ii) PTH1-34,
as the sole bioactive factor; and iii) hydroxyapatite. The spinal
fusion is selected from the group consisting of cervical and
lumbar vertebrae fusions.
(Ans. 3–4.) Our consideration of the merits of the appealed rejections is
limited to the elected species. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461
(BPAI 1987).
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REJECTION(S)
A. Claims 1, 2, 4, 5, 9, and 10 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Schense2 and Lane.3 (Ans. 5.)
B. Claims 27 and 28 are rejected under pre-AIA 35 U.S.C. § 103(a) as
being unpatentable over Schense, Lane, and Zdeblick.4 (Ans. 7.)
C. Claims 1, 2, 4, 5, 9, and 10 are rejected on the ground of nonstatutory
obviousness-type double patenting as being unpatentable over claims
1–3, 5–12, 16, and 18 of U.S. Patent No. 8,575,101 (the ’101 patent),
in view of Lane. (Ans. 3.)

DISCUSSION
A. Issue
The same issue is dispositive of all of the rejections; we therefore
consider the rejections together.
The Examiner finds that Schense, as well as claims 1–3, 5–12, 16, and
28 of the ’101 patent, disclose almost all of the elements of the methods
recited in appealed claims 1, 2, 4, 5, 9, and 10, except that they do not
explicitly disclose that the bone segments or bones being joined are spinal
lumbar vertebral bones. (Ans. 4, 6.) However, the Examiner finds that Lane
discloses “a method of spinal fusion of two distinct lumbar vertebral bones
comprising providing a . . . pharmaceutical composition comprising PTH1-34

2 Schense et al., US 2006/0148704 A1, published July 6, 2006.
3 Joseph M. Lane et al., PTH(1-34) Stimulates Spine Fusion, Poster Abstract,
The Sixth International Symposium on Osteoporosis: Current Status and
Future Directions (Apr. 6–10, 2005), http://nof.confex.com/nof/2005/
techprogram/P132.HTM.
4 Thomas A. Zdeblick et al., Interbody Cage Devices, 28 SPINE S2 (2003).
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in a bone graft matrix.” (Id. at 4, 6.) The Examiner concludes that, “[s]ince
Lane . . . disclose[s] that PTH1-34 significantly improves the rate and quality
of lumbar spinal fusions, resulting in an improved quantity of bone mass
formed in the fusion,” a skilled artisan would be motivated to employ the
method of Schense and/or claims 1–3, 5–12, 16, and 18 of the ’101 patent
for spinal fusion, “with the reasonable expectation that the resulting method
will successfully facilitate spinal fusion with an improved rate and improved
quantity of bone mass formed.” (Id. at 5, 6–7.)
Appellant contends among other things that a skilled artisan would not
have a reasonable expectation of success of combining Schense with Lane to
arrive at the claimed invention. (Appeal Br. 15.) Citing to the Lane
Declaration5 and Boden,6 Appellant argues that a skilled artisan would
understand that “[t]he microenvironment of a bone fracture site is different
from the microenvironment of a site in need of spinal fusion” and that a
skilled artisan would expect such biological differences to “influence healing
or the performance of a bone graft substitute at those sites.” (Id. at 17.)
Appellant makes similar arguments with respect to the obviousness-type
double patenting rejection over certain claims of the ’101 patent in view of
Lane. (Id. at 28.)
The issue with respect to the rejections is whether a skilled artisan
would have had a reasonable expectation of success of combining Schense
or the claims of the ’101 patent with Lane to arrive at the claimed invention.

5 Declaration of Joseph M. Lane under 37 C.F.R. § 1.132 (Dec. 9, 2014).
6 Scott D. Boden, Overview of the Biology of Lumbar Spine Fusion and
Principles for Selecting a Bone Graft Substitute, 27 SPINE S26 (2002).
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B. Analysis
On balance, we find Appellant has the better argument.
Schense teaches that matrices comprising PTH “decrease the time of
healing compared to autograft and[/]or trigger healing of bone fractures
which otherwise would not heal.” Schense Abstract. Lane teaches that
PTH1-34 stimulates spine fusion when administered after bilateral spine
fusion surgery using iliac crest autograft as bone graft. Lane 1 (Materials
and Methods); Lane Decl. ¶¶ 4, 6.
However, in light of Boden and the Lane Declaration, we agree with
Appellant that these teachings do not provide a skilled artisan with a
reasonable expectation that a pharmaceutical composition comprising matrix
forming materials and PTH1-34, without “any additional added peptide or
protein bioactive factor with bone forming properties” such as those present
in an autograft, see, e.g., Lane Decl. ¶ 5 (stating that autograft contains
bone-growing cells and proteins), would nevertheless successfully “achieve
bone formation between the vertebrae[s]” as required by the claims.
In particular, Dr. Lane explains that spinal fusion differs from healing
bone fracture because in “a bone fracture . . . the bone starts intact” and
“[t]he body responds . . . with the production of several growth factors that
attract stem cells and stimulate their proliferation and differentiation into
osteoblasts that lead to bone healing,” whereas “[s]pine fusion requires de
novo production of bone in a location without any prior bone bridging.” Id.
¶¶ 8, 10, 11. Dr. Lane states that, given the above, “[t]he fact that a
composition was effective in inducing bone formation in bone fractures . . .
provides no basis for expecting the same treatment to work in spinal
fusions,” and further provides an example of a factor (anti-sclerostin
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antibodies) that enhances fracture healing but has no effect in spinal fusion.
Id. ¶¶ 10, 11. Finally, Dr. Lane cites to Whitfield7 as teaching that
“[c]ontinuous systemic delivery of PTH is not known in the art to produce
de novo bone synthesis in a void,” because Whitfield states that “[n]o PTH
can restore the original bone structure” and that “[t]hey cannot generate
trabeculae de novo or make broken trabeculae rejoin if they have drifted too
far apart.” Lane Decl. ¶ 7; Whitfield 8.
The statements in the Lane Declaration are supported by the art cited
by Appellant. Boden, for instance, teaches that
different healing environments (e.g., metaphyseal defect, long
bone fracture, interbody spine fusion and posterolateral spine
fusion) have increasing levels of difficulty in forming new
bone. For example, a metaphyseal defect permits the successful
use of many purely osteoconductive materials. In contrast, a
posterolateral spine fusion environment generally does not
tolerate the use of purely osteoconductive materials as stand-
alone substitutes, and only sometimes permits their use as bone
graft extenders. Thus, validation of any bone graft substitute in
one clinical anatomic site may not be predictive of its
performance in another location. Accordingly, surgeons must
be very careful in using graft substitutes that have not been
tested definitively in the particular healing environment
wherein they are about to use it.
Boden 29, left column. Boden further teaches that “successful bone
induction at any level does not infer success at the next most stringent
level.” Id. at S30, left column.

7 James F. Whitfield et al., The Parathyroid Hormones: Bone-Forming
Agents for Treatment of Osteoporosis, MEDSCAPE,
http://www.medscape.com/viewarticle/408928 (last visited Oct. 15, 2019).
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The Examiner asserts that Appellant improperly argues the references
cited in the rejection separately and also misconstrued the prior art rejection
of record. The Examiner asserts that
the . . . prior art rejection of record is based on employing the
Schense method, i.e. administering PTH1-34 in their “bone graft
substitute”, for spinal fusion, based on Lane’s disclosure that
administering PTH1-34 in a bone graft (i.e. autograft in their
case) successfully stimulates spinal fusion, with the knowledge
from Schense that their “bone graft substitute” is functionally
equivalent to autograft as far as promoting successful bone
formation, regeneration, and repair, but has the advantage over
autograft of a decreased time of healing.
Ans. 12.
We are not persuaded. The explanation above fails to address the
crux of Appellant’s argument, namely that Schense and Lane address the use
of PTH1-34 in two different physiological environments (i.e., bone fracture
and spinal fusion, respectively), and there is no reasonable expectation that
PTH1-34 would function in the same manner in both. Thus, even if Schense’s
PTH1-34-containing bone graft substitute is considered functionally
equivalent to autograft in the context of healing bone fractures, the Examiner
has not persuasively explained why, in light of the evidence cited by
Appellant, a skilled artisan would consider Schense’s PTH1-34-containing
bone graft substitute to be functionally equivalent to autograft in the context
of a spinal fusion procedure.
The Examiner asserts that
[t]he Schense method and the presently claimed method both
fundamentally involve the joining/fusing to two adjacent bones
together by administering at the site between the two adjacent
bones to be joined/fused the very same composition. Schense
specifically joins two distinct bone segments together at a point
of discontinuity, such as a fracture, via bone formation to thus
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repair the fracture. Anyone of ordinary skill in the art would
know that a “discontinuity” is a “gap” between two bones.
Schense does not expressly place any necessary limit on the
size of the “discontinuity” or “gap” that can be treated. While
PTH alone (i.e. in the absence of matrix) may not be effective
in facilitating bone formation across larger gaps, as Appellant
points out, in the instant case where PTH is associated with a
bone graft matrix, and this composition is administered to fill
the space within the gap, there would appear to be no limit on
the size of the gap that can be successfully treated. Thus, one
of ordinary skill in the art would find no reason why the
Schense method could not be successfully employed for spinal
fusion by administering their composition to fill the gap
between the two vertebral bones.
Ans. 13–14.
We are not persuaded. The Examiner appears to be responding in part
to the statements in Whitfield, cited in the Lane Declaration, that PTH
cannot “restore the original bone structure,” “generate trabeculae de novo,”
or “make broken trabeculae rejoin if they have drifted to far apart.” Lane
Decl. ¶ 7; Whitfield 8. However, the Examiner has not persuasively
addressed the evidence provided by Appellant, in the form of Boden
reference and the Lane Declaration, that even the same composition may not
act in the same manner with respect to bone formation, depending on the
particular environment—e.g., bone fracture versus spinal fusion—in which
the bone formation is expected to take place. “[R]ejections on obviousness
grounds cannot be sustained by mere conclusory statements; instead, there
must be some articulated reasoning with some rational underpinning to
support the legal conclusion of obviousness.” KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 418 (2007) (quoting In re Kahn, 441 F.3d 977, 988 (Fed. Cir.
2006) (internal quotation marks omitted)).
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The Examiner also asserts that, even though Lane uses autograft in the
spinal fusion, its title teaches that “PTH1-34 stimulates spine fusion,” and it
further reports that “‘PTH administration . . . increases the rate of spine
fusion by 170% and increases the mass of bone formation by 75%” and that
“PTH has potential to . . . improve the rate of fusion and improve the quality
of bone mass formed in the fusion’.” Ans. 12. The Examiner asserts that,
[c]learly, one of ordinary skill in the art would understand from
this report that PTH is responsible for these reported effects, not
specific cells or proteins in the autograft. Hence, there is
absolutely no reason why one of ordinary skill in the art would
not reasonably expect the PTH in Schense to have the very
same affect, based on the understanding and evidence that their
“bone graft substitute” is functionally an equivalent substitute
for bone graft (i.e. iliac crest autograft in this case). In support
of this, Schense discloses that PTH1-34 exhibits bone formation
properties when included in either natural or synthetic matrices.
Id. at 12–13.
We are not persuaded. Although Lane teaches that PTH1-34 stimulates
spine fusion, it does so in a context in which autograft is used as bone graft.
Given Appellant’s evidence that there is no reasonable expectation PTH1-34
would function in the same manner in healing bone fracture and in spinal
fusion, the Examiner has not persuasively explained why a skilled artisan
would reasonably expect PTH1-34 to stimulate spine fusion—which requires
de novo bone formation, Lane Decl. ¶ 11—in the absence of autograft,
merely because Schense teaches that PTH1-34-containing matrices exhibit
bone formation properties and may function as a bone graft substitute in the
context of healing bone fractures.
The Examiner points out that the Specification teaches that patients in
need of spinal fusion include those with spinal fracture. Ans. 13. The
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Examiner states that, thus, “the microenvironment in which the Schense
method has proven successful, i.e. fracture, is the very same as at least one
microenvironment encompassed by the instant claims, i.e. fracture.” Id.
We are not persuaded. The Specification defines spinal fusion as “a
surgical procedure aimed at achieving bone formation and thereby fusion
between two or more adjacent vertebrae.” Spec. 10:12–14. While a spinal
fracture may be treated with spinal fusion surgery, the Examiner cites no
persuasive evidence that spinal fusion, as used in the treatment of a spinal
fracture, is the same as the procedure of healing the fracture, which is the
subject of the Schense reference.
Finally, the Examiner asserts that obviousness does not require an
absolute guarantee or proof of success but rather a “reasonable expectation”
of success. Ans. 14. While we agree with the Examiner that “the
expectation of success need only be reasonable, not absolute,” Pfizer, Inc. v.
Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007), we agree with Appellant
that the Examiner has not persuasively explained why, in light of the Lane
Declaration and the Boden reference, a skilled artisan would have a
reasonable expectation that a pharmaceutical composition comprising
matrix forming materials and PTH1-34, without “any additional added peptide
or protein bioactive factor with bone forming properties,” would
successfully “achieve bone formation between the vertebrae[s],” as required
by the claims.
Accordingly, we reverse the Examiner’s rejection of claims 1,
2, 4, 5, 9, and 10 as obvious over Schense and Lane. The Examiner
cites Zdeblick only for the limitations in dependent claims 27 and 28
regarding the use of an “interbody spinal fusion cage.” Ans. 8–10.
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We therefore reverse the rejection of claims 27 and 28 as obvious over
Schense, Lane, and Zdeblick for the same reasons. In re Fine, 837
F.2d 1071, 1076 (Fed. Cir. 1988) (“Dependent claims are nonobvious
under section 103 if the independent claims from which they depend
are nonobvious.”). Finally, the Examiner’s obviousness-type double
patenting rejection of claims 1, 2, 4, 5, 9, and 10 over claims 1–3, 5–
12, 16, and 18 of the ’101 patent largely tracks the rejection of these
claims over the combination of Schense and Lane.8 Thus, we reverse
the obviousness-type double patenting rejection for the reasons
already discussed.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis  Affirmed Reversed
1, 2, 4, 5, 9,
10
103(a) Schense, Lane

1, 2, 4, 5, 9,
10
27, 28 103(a) Schense, Lane,
Zdeblick

27, 28

8 The Examiner points out that claim 3 of the ’101 patent specifically recites
a method of repairing a bone fracture wherein the bone fracture is a fracture
of the vertebrae. Ans. 4. However, as discussed above with respect to the
obviousness rejection over Schense and Lane, the Examiner has not
persuasively shown that, in light of the evidence cited by Appellant, a skilled
artisan would reasonably expect PTH1-34 to function in the same manner
with respect to spinal fusion as compared to repairing a bone fracture, even
if the bone fracture is a fracture of the vertebrae.

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Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis  Affirmed Reversed
1, 2, 4, 5, 9,
10
Claims 1–3, 5–12,
16, 18 of U.S.
Patent No.
8,575,101, Lane
1, 2, 4, 5, 9,
10
Overall
Outcome
1, 2, 4, 5, 9,
10, 27, 28

REVERSED