Ex Parte Nataraj et al

Patent Trial and Appeal Board

Jul 21, 2016

12349392 (P.T.A.B. Jul. 21, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/349,392 0110612009
96270 7590 07/25/2016
Baxter Healthcare Corporation (BFF LLP)
Bozicevic, Field & Francis
1900 University Avenue, Suite 200
SUITE 200
East Palo Alto, CA 94303
FIRST NAMED INVENTOR
Chandrasekaran NATARAJ
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.
BXSY-039DIV 4935
EXAMINER
NGUYEN, QUANG
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
07/25/2016 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
following e-mail address( es):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CHANDRASEKARAN NATARAJ,
GREGG RITTER, and THOMAS SANDER
Appeal2014-005015
Application 12/349,392
Technology Center 1600
Before MELANIE L. McCOLLUM, JEFFREY N. FREDMAN, and
ROBERT A. POLLOCK, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a
bioimplant. The Examiner rejected the claims as obvious and on grounds of
double-patenting. We have jurisdiction under 35 U.S.C. § 6(b). We reverse
the obviousness rejection but affirm the double-patenting rejection.
1 Appellants identify the Real Party in Interest as Baxter International Inc.
(see App. Br. 3).
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Application 12/349,392
Statement of the Case
Background
"Natural tissue bioimplants are gaining acceptance as advantageous
alternatives to synthetic implants in many surgical procedures. Among other
advantages, bioimplants more closely resemble in size, shape and
performance the biological structures that they are designed to replace than
do synthetic implants" (Spec. i-f 2).
The Claims
Claims 1, 3, 9, 10, and 71-77 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A chemically sterilized bioimplant comprising a
biological tissue and at least one protein adjunct conjugated
thereto, wherein the biological tissue is processed tissue in
native form and comprises crosslinked de-cellularized collagen,
and wherein the bioimplant is chemically sterilized using
carbodiimde [sic].
The Issues2
The Examiner rejected claims 1, 3, 9, 10, and 71-77 under 35 U.S.C.
§ 103(a) as obvious over Hendriks3 and Girardot4 (Non-Final Act5. 4--8).
2 We note that the claims are subject to a restriction requirement and that
Appellants elected a bioimplant comprising processed tissue in native form,
specifically decellularized collagen, and an adjunct comprising proteins (see
Response to Restriction filed Jan. 23, 2012). Accordingly, we limit our
consideration of this record to Appellants' elected species, and we take no
position respecting the patentability of Appellants' claimed composition as
it may relate to the remaining, non-elected species. Cf Ex parte Ohsaka, 2
USPQ2d 1460 (BPAI 1987).
3 Hendriks et al., US 6,117,979, issued Sept. 12, 2000.
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B. The Examiner rejected claims 1, 3, 9, 10, and 71-77 on the ground of
nonstatutory obviousness-type double patenting as being unpatentable over
claims 1, 73-75, 78, 80, and 82-88 of copending Application No.
12/827,896 (now issued as Nataraj et al., US 9,272,004, Mar. 1, 2016) (Non-
Final Act. 12-13).
A. 35 U.S.C. § 103(a) over Hendriks and Girardot
The Examiner finds that Hendriks teaches "preparation of a
bioprosthetic device or implant (e.g., heart valves and vascular grafts)
derived in whole or in part from natural tissues that contain collagen-based
material ... that is crosslinked with an epoxy functionalized crosslinking
agent ... through a portion of the collagen carboxyl groups" (Non-Final Act.
4--5). The Examiner finds that Hendriks teaches that "subsequent to
crosslinking collagen-based materials with the epoxy functionalized
crosslinking agents, additional crosslinking reactions to increase the
crosslink density via a variety of known crosslinking techniques, including
through the use of carboxyl group activating agent such as carbodiimide"
may be employed (Non-Final Act. 5; emphasis omitted).
The Examiner acknowledges that Hendriks does "not teach
specifically that the bioprosthetic device or implant is subjected to
chemically sterilization by carbodiimide." (Non-Final Rej. 6; emphasis
omitted).
4 Girardot et al., US 6,521,179 Bl, issued Feb. 18, 2003.
5 We refer to the Non-Final Action mailed Nov. 30, 2012.
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Application 12/349,392
The Examiner finds that Girardot teaches "that medical products
which consist or incorporate biological tissue, such as allografts or prosthetic
tissue valves such as tissue valves constructed from bovine pericardium,
require sterilization prior to packaging or prior to implantation into a
patient" (Non-Final Rej. 6; emphasis omitted). The Examiner finds that
Girardot teaches "a biological tissue that has been rendered acellular either
before or after cross-linking" (Id.; emphasis omitted).
The Examiner finds it obvious "to modify the teachings of Hendri[]ks
et al. by also subjecting their disclosed bioprosthetic devices or implants to
[] chemically sterilization treatment conditions as taught by Girardot et al
prior to packaging or prior to implantation into a patient in light of the
teachings of Girardot et al." (Non-Final Act. 7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Hendriks and Girardot render
the claims obvious?
Findings of Fact
1. Hendriks teaches "a bioprosthetic device, which is derived in
whole or in part from natural tissues that contain collagen-based materials"
(Hendriks, col. 5, 11. 32-34).
2. Hendriks teaches that "collagen-based materials include whole
tissue (i.e., tissue containing collagen and noncollagenous substances or
cells), only the collagen matrix without the noncollagenous substances, and
purified fibrous collagen" (Hendriks, col. 5 11. 38--43).
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3. Hendriks teaches that "[b]locking of the collagen free amine
groups may significantly reduce the antigenicity of the material" (Hendriks,
col. 6, 11. 52-53).
4. Hendriks teaches that "the biocompatibility of this material can
also be improved by blocking the amine groups with appropriate
biologically active molecules, such as for instance, the very blood
compatible molecule heparin" (Hendriks, col. 11, 11. 42--45).
5. Hendriks teaches
a material can be produced that actively participates in the host-
material interaction, thereby enhancing the acceptance and
performance of the material. A wide variety of known
biomolecules can be used according to the present invention.
Examples include, but are not limited to, angiogenic factors,
growth factors, antimicrobial agents, antithrombotic agents, and
anticalcification agents.
(Hendriks, col. 7, 11. 6-13).
6. Girardot teaches that
medical products which include biological tissue, e.g.
allografts and xenografts ... can be effectively sterilized by
treatment with a bactericidal coupling agent of the type
known to create amide linkages between amines and
carboxyl moieties in a manner so that there is either no
significant change or a closely controllable change in the
physical character of the biological material being sterilized.
(Girardot, col. 1, 11. 49-59).
7. Girardot teaches that "[m]edical products which consist of or
incorporate biological tissue require sterilization prior to packaging or prior
to implantation into a patient" (Girardot, col. 2, 11. 51-53).
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8. Girardot teaches that the "preferred coupling agent is 1-ethyl-
3(3-dimethyl aminopropyl)carbodiimide hydro-chloride (EDC)" (Girardot,
col. 3, 11. 46-48).
9. Girardot teaches that "[a]lthough the blocking agents described
above may be best suited during sterilization, other carboxyl or
amineblocking agents can be reacted with tissue amine or carboxyl groups
before sterilization" (Girardot, col. 13, 11. 38--41).
10. Malaviya6 teaches that "[i]t will be appreciated that the cross-
linking agent is chosen such that it is non-reactive with the biological agent.
For example, carbodiimide reacts with hydroxyl, amine, or carboxylate
groups" (Malaviya i-f 7 6).
11. Murphy7 teaches that "[i]ncubation of micromolar ATP-EDC
[l-ethyl-3-[3-( dimethylamino )propyl] carbodiimide] with SR ATPase
resulted in rapid loss of activity" (Murphy 11238, col. 1 to 2).
12. Okada8 teaches that "EDC, which is a modifier for carboxyl
groups, inactivated the enzyme rapidly, but the inactivation did not proceed
to completion" (Okada 482, col. 2).
6 Malaviya et al., US 2003/0049299 Al, published Mar. 13, 2003.
7 Murphy, A., Reaction of a Carbodiimide Adduct of ATP at the Active Site
of Sarcoplasmic Reticulum Calcium ATPase, 29 BIOCHEMISTRY 11236-
11242 (1990).
8 Okada et al., Mode of Inactivation of Putrescine Oxidase by l-Ethyl-3-(3-
dimethylaminopropyl)carbodiimide or Metal Ions, 88 J. BIOCHEMISTRY
481--488 (1980).
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Principles of Law
A "reference may teach away from a use when that use would render
the result inoperable." In re Icon Health and Fitness, Inc., 496 F.3d 1374,
1381 (Fed. Cir. 2007).
Analysis
Appellants contend that "one of skill in the art would have no
motivation to use Girardot's method to sterilize a bioimplant that had been
linked to a protein adjunct" "because Girardot's sterilization method relies
on the use of a coupling agent that has been long known to inactivate
proteins" (App. Br. 5). Appellants contend that:
Based on the data provided by Okada and Murphy, one of skill
in the art would recognize that proteins are extremely sensitive
to carbodiimide. One of skill in the art would have no
motivation to sterilize an implant that contains a protein adjunct
using Girardot' s method because Girardot' s sterilization
conditions are at least two orders of magnitude more harsh than
the protein-inactivating conditions identified by Okada and
Murphy.
(App. Br. 7).
The Examiner responds that "the claims also do not require that the
protein adjunct has to retain 100% of all of its biological activities, or 100%
of any particular biological activity in a multifunctional protein" (Ans. 4;
emphasis omitted), that the references show crosslinking with EDC only
partially inactivates enzymes (Ans. 5-9), and that "an ordinary skilled
artisan would also subject the bioprosthetic device or implant taught by
Hendriks et al to the sterilization method of Girardot et al prior to the
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crosslinking process with an epoxy functionalized crosslinking agent"
(Ans. 7).
The Examiner further finds that "without substantial stiffening over
time, it does not necessarily mean that the coupled bioactive molecules to
the collagen matrix are permanently linked to such device or implant; and
that the active biomolecules would not be released over time as argued by
Appellants" (Ans. 11 ).
We find that Appellants have the better position. The Examiner's
rejection is predicated on Hendriks' teaching of biomolecules as inherently
comprising proteins as adjuncts on the bioimplant (FF 5). Thus, the
evidence of Murphy and Okada is directly relevant to the question of
whether the ordinary artisan would have been motivated to apply Girardot's
sterilization process to Hendriks bioimplant containing a protein adjunct.
The Examiner provides no evidence that the biomolecules of Hendriks
would achieve Hendriks' goal of producing a material "that actively
participates in the host-material interaction, thereby enhancing the
acceptance and performance of the material" (FF 5). We do not find it
necessarily inherent that proteins that function as angiogenic factors, growth
factors, antimicrobial agents, antithrombotic agents, or anticalcification
agents would retain activity to serve the function of enhancing acceptance of
the bioimplant after chemical treatments that substantially abolish enzyme
activity (FF 11-12). "Inherency ... may not be established by probabilities
or possibilities. The mere fact that a certain thing may result from a given
set of circumstances is not sufficient." MEHL/Biophile Int 'l. Corp. v.
Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999).
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We also do not find the Examiner's timing argument persuasive. 9
Girardot teaches blocking agent reaction prior or during sterilization (FF 9),
but the Examiner does not identify any suggestion in either Hendriks or
Girardot to sterilize the tissue and then crosslink. The Examiner provides no
reason to reverse the order taught by the cited prior art and sterilize the
implant in the middle of the preparation process rather than when the
implant preparation process has been completed.
Finally, even if the Examiner is correct that there is some low level of
sterilization agent that would not fully ablate the protein activity, Okada and
Murphy clearly demonstrate prior art teachings away from sterilizing
Hendriks' protein containing bioimplant with the agent of Girardot. See In
re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994) ("A reference may be said to
teach away when a person of ordinary skill, upon reading the reference,
would be discouraged from following the path set out in the reference, or
would be led in a direction divergent from the path that was taken by the
applicant.) Here, the ordinary artisan familiar with Hendriks, Girardot,
Malaviya, Okada, and Murphy would be discouraged from sterilizing
Hendriks' bioimplant with the carbodiimide agent.
9 We recognize that Appellants' Specification teaches sterilization prior to
addition of adjuncts (Spec. i-f 7 6), but the Examiner must find evidence in
the prior art suggesting an otherwise unobvious order of sterilization and
adjunct addition, and cannot rely upon Appellants' Specification.
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Conclusion of Law
The evidence of record does not support the Examiner's conclusion
that Hendriks and Girardot render the claims obvious.
B. Provisional Obviousness-type double patenting
Appellants request that we hold the Examiner's provisional double
patenting rejections in abeyance pending the identification of allowable
subject matter (App. Br. 12). However, "[i]f a ground of rejection stated by
the examiner is not addressed in the appellant's brief, that ground of
rejection will be summarily sustained by the Board." MPEP § 1205.02 (8th
ed., July 2010); see also MPEP § 1205.02 (9th ed., March 2014).
To hold the provisional double patenting in abeyance, as Appellants
request, could result in inefficient piecemeal examination and delay,
particularly here, where the issuance of 12/827,896 means the rejection is no
longer provisional. We summarily affirm the Examiner's provisional double
patenting rejection of claims 1, 3, 9, 10, and 71-77 because Appellants do
not present arguments or evidence showing error in the rejection.
SUMMARY
In summary, we reverse the rejection of claims 1, 3, 9, 10, and 71-77
under 35 U.S.C. § 103(a) as obvious over Hendriks and Girardot.
We affirm the rejection of claims 1, 3, 9, 10, and 71-77 on the ground
of nonstatutory obviousness-type double patenting as being unpatentable
over claims 1, 73-75, 78, 80, and 82-88 of copending Application No.
12/827,896 (now issued as Nataraj et al., US 9,272,004, Mar. 1, 2016).
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l).
AFFIRMED
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