Ex Parte Serhan et al

Patent Trial and Appeal Board

May 26, 2016

11881925 (P.T.A.B. May. 26, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
111881,925 07/30/2007
21005 7590 05/31/2016
HAMILTON, BROOK, SMITH & REYNOLDS, P.C.
530 VIRGINIA ROAD
P.O. BOX 9133
CONCORD, MA 01742-9133
Hassan Serhan
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
3518.1012-030 2561
EXAMINER
HA YES, ROBERT CLINTON
ART UNIT PAPER NUMBER
1649
NOTIFICATION DATE DELIVERY MODE
05/31/2016 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HASSAN SERBAN, THOMAS M. DIMAURO, MOHAMED
ATTA WIA, and GREGORY COLLINS 1
Appeal2014-001805
Application 11/881,925
Technology Center 1600
Before DONALD E. ADAMS, JOHN G. NEW, and RICHARD J. SMITH,
Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
formulation for treating degenerative disc disease. We have jurisdiction
under 35 U.S.C. § 6(b ).
We affirm.
1 According to Appellants, the real party in interest is DePuy Synthes
Products, LLC. (Appeal Br. 1.)
Appeal2014-001805
Application 11/881,925
STATEMENT OF THE CASE
Background
"The natural intervertebral disc contains a jelly-like nucleus pulposus
surrounded by a fibrous annulus fibrosus." (Spec. 1, 11. 10-11.)
"In other instances of [disc degenerative disease], genetic factors or
apoptosis can also cause the cells within the nucleus pulposus to emit toxic
amounts of [] cytokines and MMPs2 ... As [disc degenerative disease]
progresses, toxic levels of the cytokines and MMPs present in the nucleus
pulposus begin to degrade the extracellular matrix." (Id. at 2, 11. 5-14.)
Claims on Appeal
Claims 1, 2, 4, 5, 9, 12-16, and 18 are on appeal. (Appeal Br. 18-19.)
Claim 1 is illustrative and reads as follows:
1. A formulation for treating degenerative disc disease, comprising:
a) tissue inhibitor of matrix metalloproteinase (TIMP)-1 or
Til\1P-2; and
b) an additional therapeutic agent selected from the group
consisting of:
i) transforming growth factor-B (TGF-B);
ii) fibroblast growth factor-2 (FGF-2), and
iii) mesenchymal stem cells.
Examiner's Rejections
1. Claims 1and14 stand rejected under 35 U.S.C. § 103(a) as obvious
over Goupille. 3 (Ans. 2.)
2 MMPs refers to matrix metalloproteinases. (Spec. 1, 1. 19.)
3 Goupille et al., Matrix Metalloproteinases: The Clue to Intervertebral Disc
Degeneration?, 23 SPINE 14, 1612-26 (1998) ("Goupille").
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We vacate this Rejection No. 1 as cumulative to the more
comprehensive Rejection No. 2 below, and Rejection No. 1 will not be
discussed further.
2. Claims 1, 2, 4, 5, 9, 12-16, and 18 stand rejected under 35 U.S.C.
§ 103(a) as obvious over Goupille and Ferree. 4 (Id.)
FINDINGS OF FACT
We adopt as our own the Examiner's findings and analysis concerning
the scope and content of the prior art. The following findings are included
for emphasis and reference convenience.
FF 1. Goupille teaches tissue inhibitors of MMPs (TIMPs ), and that TIMP-1
and TIMP-2 "specifically inhibit [MMPs] enzymatic activity." (Goupille 4.)
FF 2. Goupille teaches that TGF-B inhibits the synthesis of MMPs, and that
TGF-B stimulates production of TIMP-1. (Id. at 4--5.)
FF 3. The Examiner finds that Ferree teaches treating degenerative disc
disease using harvested/concentrated autologous nucleus pulpous
chondrocyte-like cells, which include "precursor cells ... that could
differentiate into cells to build a functional nucleus pulposus or annulus
fibrosis" (i.e., mesenchymal stem cells), along with additional therapeutic
substances that include TGF-B. (Final Act. 5 6, citing Ferree col. 2, 11. 28-33
and col. 3, 11. 14--46.)
FF 4. The Specification states that "when viable cells are selected as the
additional therapeutic substance, the viable cells comprise mesenchymal
stem cells (MS Cs). MSCs provide a special advantage for administration
4 Ferree, US 6,340,369 Bl, issued Jan. 22, 2002 ("Ferree").
5 Office Action dated July 12, 2012.
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Application 11/881,925
into a degenerating disc because it is believed that ... they have the ability
to proliferate and differentiate into the desired cells." (Spec. 16, 11. 8-13.)
FF 5. The Examiner finds that a formulation "volume of 0.01---0.03 [ml]
would appear to be an optimized volume to minimize any adverse effects
from administering too much" TIMP-1 or TIMP-2, mesenchymal stem cells,
and TGF-B into an intervertebral disc. (Final Act. 6.)
ISSUES
Whether a preponderance of the evidence of record supports the
Examiner's conclusion of obviousness under 35 U.S.C. § 103(a).
DISCUSSION
The Examiner concluded that it would have been obvious to one of
ordinary skill in the art to complement Goupille's TIMP-1 and/or TIMP-2
formulation to include Ferree's mesenchymal stem cells, along with TGF-B
as taught by both Goupille and Ferree. (Final Act. 6.) This conclusion was
based on Ferree's teaching that mesenchymal stem cells and TGF-B can treat
disc degenerative disease, and because Goupille teaches that TGF-B either
stimulates TIMP production or suppresses matrix [ metalloproteinase]
synthesis. (Id.) Furthermore, the Examiner found that it would have been
prima facie obvious to make such an improved formulation, to potentially
treat intervertebral disc degenerative disease, "in which a volume of [0.1---0.3
ml] would appear to be an optimized volume to minimize any adverse
effects" from administration of too much TIMP, mesenchymal stem cells,
and TGF-B into an intervertebral disc. (Id.)
We find that the Examiner has satisfied the burden of showing "some
articulated reasoning with some rational underpinning to support the legal
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Application 11/881,925
conclusion of obviousness." KSR Int? Co. v. T'elejlex Inc., 550 U.S. 398,
418 (2007). Moreover, the Examiner has established a prima facie case of
obviousness and, as discussed below, Appellants have not overcome that
prima facie case.
We address at the outset Appellants' concern that "the Examiner is
applying an improper legal standard" in regards to motivation, specifically
with respect to the Examiner's statement that "there is no requirement for
the Examiner's motivation to be the same as Applicants." (Appeal Br. 6, 9,
referencing Final Act. 4.) It is well settled that "the law does not require that
the references be combined for the reasons contemplated by the inventor."
In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992) (citing cases).
Accordingly, we find no application of an improper legal standard on the
record before us.
Claims 1 and 9
Teaching Away
Appellants argue that Goupille teaches away from the claimed
formulation. (Appeal Br. 9--10; Reply Br. 4--5.) In support of that
argument, Appellants reference Goupille' s statements that "[ e ]xperiments
performed in animal models with exogenous TIMPs had mixed results" and
"it is uncertain whether administration of exogenous TIMPs will be useful
therapeutically." (Id. at 9, citing Goupille 10.) Appellants also reference
Goupille' s teaching that direct administration of a growth factor to stimulate
TIMP production would raise the problem of how to "avoid some of [the
growth factor's] generalized effects." (Id. at 10, citing Goupille 10.)
We are not persuaded by Appellants' arguments. "[I]n general, a
reference will teach away if it suggests that the line of development flowing
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from the reference's disclosure is unlikely to be productive of the result
sought by the applicant." In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
That is not the case here. Goupille clearly teaches the beneficial properties
of TIMPs and TGF-B with regard to MMPs. (FF 1, 2.) Goupille's statement
regarding "mixed results" (i.e. some positive, some negative) in that context
suggests further development may be productive. Moreover, given that
obviousness only requires a reasonable expectation of success, a statement
of "uncertain" usefulness or an issue to be addressed (i.e. "generalized
effects" of growth factor) in the context of Goupille's entire teaching does
not constitute a teaching away. See Gurley, 27 F.3d at 553; see also In re
O'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988) ("Obviousness does not
require absolute predictability of success. Indeed, for many inventions that
seem quite obvious, there is no absolute predictability of success until the
invention is reduced to practice.").
Combination of TIMPs and TGF-fJ
Appellants argue that Goupille does not teach using TIMPs together
with TGF-B, and that at most it describes use of these agents as an
"alternative approach." (Appeal Br. 10.) Furthermore, according to
Appellants, "Ferree does not provide the missing motivation to select and
combine two alternative treatments." (Id. at 12.)
We are not persuaded. The test for obviousness is what the combined
teachings of Goupille and Ferree would have suggested to one of ordinary
skill in the art. See In re Keller, 642 F.2d 413, 425 (CCPA 1981) (citing
cases). Goupille teaches the effective properties of both TIMPs and TGF-B,
including that TGF-B stimulates production of TIMP-1 (FF 1, 2), and Ferree
teaches the combination of TGF-B with other therapeutic substances, such as
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MSCs (FF 3).
Hindsight
Appellants argue that the Examiner's rejection is based on improper
hindsight. (Appeal Br. 8-10.) We are not persuaded. Any concern
regarding hindsight bias is obviated because the Examiner points to specific
disclosures in the prior art that give a reason or motivation to make the
claimed formulation. See Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d
1280, 1292 (Fed. Cir. 2012).
Claims 2, 4, and 5
Appellants argue further that Ferree does not describe MSCs, and that
MSCs are lacking from Goupille. (Appeal Br. 13; Reply Br. 7.)
Furthermore, Appellants argue that even if Ferree describes a genus of cell
types that encompassed MSCs, it would not be a specific teaching of the
species MSCs, as provided in Appellants' claims. (Id.)
\Ve are not persuaded. A person of ordinary skill in the art would
understand Ferree's description of precursor cells (FF 3) as teaching or
suggesting MSCs as claimed by Appellants (FF 4). 6 Moreover, to the extent
a genus/species (or subgenus) relationship could be characterized to exist as
between Ferree's precursor cells and Appellants MSCs, the prior art
precursor cells would appear to be a species or subgenus within the claimed
6 Consideration of Appellants' Specification is proper in order to interpret
the claimed term "mesenchymal stem cells" because claims under
examination are given their broadest reasonable interpretation consistent
with the specification, as interpreted by one of ordinary skill in the art. See
In re Am. Academy of Sci. Tech Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004).
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MSC genus, thereby barring any patentable weight to be given to the
claimed MSC genus. See In re Slayter, 276 F.2d 408, 411(CCPA1960).
Claims 12 and 13
Appellants argue further that Ferree only describes using cultured
cells, whereas the claimed MSCs are uncultured cells. (Appeal Br. 13;
Reply Br. 8.) Appellants also argue that"[ c ]ultured cells are different from
uncultured cells." (Id.) We are not persuaded. A person of ordinary skill in
the art "is also a person of ordinary creativity, not an automaton." KSR, 550
U.S. at 421 (2007). Moreover, picking one of a finite number of known
solutions to a known problem is obvious. See id. Cells may be cultured or
uncultured, and Appellants' additional claim limitation of "uncultured" cells
is simply insufficient to overcome the instant obviousness rejection.
Claims 14-16 and 18
Appellants argue further that "Ferree, like Goupille, does not teach or
fairly suggest a volume of the formulation of 0.1---0.3 ml or that the
formulation is suitable for transdiscal administration into an intervertebral
disc." (Appeal Br. 14.) We are not persuaded. Appellants define
"transdiscal administration" as including injection into a degenerating disc
(see Spec. 6, 11. 8-13) and Ferree teaches injection into the affected disc (see
Ferree col. 3, 11. 20-21). Moreover, "where the general conditions of a
claim are disclosed in the prior art, it is not inventive to discover the
optimum or workable ranges by routine experimentation." In re Aller, 220
F.2d 454, 456 (CCPA 1955). Here, the general conditions of the claimed
invention are disclosed in the prior art (e.g. injection of formulation into the
affected disc), and it is therefore not inventive to discover the optimum or
workable ranges of the formulation (0.1---0.3 ml) by routine experimentation.
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CONCLUSION OF LAW
A preponderance of evidence of record supports the Examiner's
conclusion that claims 1, 2, 4, 5, 9, 12-16, and 18 are obvious under 35 U.S.C.
§ 103(a).
SUMMARY
The rejection of claims 1, 2, 12, and 14 under 35 U.S.C. § 103(a) is
affirmed. Claim 9 is not separately argued and falls with claim 1. Claims 4
and 5 are not separately argued and fall with claim 2. Claim 13 is not
separately argued and falls with claim 12. Claims 15, 16, and 18 are not
separately argued and fall with claim 14.
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).
AFFIRMED
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