Ulf Fritz et al.

Patent Trials and Appeals Board

Oct 18, 2019

14720428 - (D) (P.T.A.B. Oct. 18, 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.
14/720,428 05/22/2015 Ulf FRITZ 8150BSC0376D1 2903
121974 7590 10/18/2019
KACVINSKY DAISAK BLUNI PLLC
America's Cup Building
50 Doaks Lane
Marblehead, MA 01945
EXAMINER
SCHLIENTZ, LEAH H
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
10/18/2019 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):
bbonneville@kdbfirm.com
docketing@kdbfirm.com
ehysesani@kdbfirm.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ULF FRITZ, OLAF FRITZ, THOMAS A. GORDY,
RONALD WOJCIK, JACQUES BLÜMMEL, and
ALEXANDER KÜLLER1
Appeal 2019-004233
Application 14/720,428
Technology Center 1600
Before ERIC B. GRIMES, JOHN E. SCHNEIDER, and DAVID COTTA,
Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of embolization, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 Appellant identifies the real party in interest as Boston Scientific Limited.
Appeal Br. 3. We use the word Appellant to refer to “applicant” as defined
in 37 C.F.R. § 1.42(a).
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STATEMENT OF THE CASE
The Specification states that “it may be advantageous to provide
specific sizes of . . . microspheres and nanospheres to a user”; for example,
to “allow for selective embolization of certain sized blood vessels.” Spec.
¶ 2. “It may further be advantageous to provide a user with color-coded
microspheres or nanospheres to allow ready identification of the sized
particles in use.” Id.
“The preferred particles of the invention . . . are composed, in whole
or in part, [of] the specific polyphosphazene polymer known as
poly[bis(trifluoroethoxy) phosphazene].” Id. ¶ 38. “[O]wing to the
biocompatible nature of the polymer, the particles facilitate avoidance or
elimination of immunogenic reactions.” Id. ¶ 39. “Moreover, it has been
found that the particles of the invention exhibit reduced biodegradation in
vivo.” Id.
Claims 13, 15, and 34–48 are on appeal. Claim 13 is representative
and reads as follows:
13. A method of embolization in a mammal, comprising:
inserting polymeric particles into a blood vessel;
wherein the polymeric particles each comprise a hydrogel
core, a dye, and a coating that comprises a polyphosphazene
selected from poly[bis(2,2,2-trifluoroethoxy)]phosphazene or a
derivative of poly[bis(2,2,2-trifluoroethoxy)]phosphazene, and
wherein the polymeric particles are of sufficient size to occlude
the blood vessel.
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OPINION
Claims 13, 15, and 34–48 stand rejected under 35 U.S.C. § 103(a) as
obvious based on Vogel2 and Grunze.3 Final Action4 3. The Examiner finds
that “Vogel teaches injectable compositions comprising biocompatible, . . .
substantially spherical polymeric material carriers which are capable of
efficiently delivering bioactive therapeutic factor(s) for use in embolization
drug therapy.” Id. The Examiner finds that Vogel’s “microspheres comprise
elastomers, preferably . . . hydrophilic copolymers . . . of the acrylic family
such as polyacrylamides and their derivatives, . . . (i.e. hydrogel
microspheres).” Id. at 5. The Examiner finds that Vogel’s microspheres can
include “a chemical dye, such as Cibacron Blue or Procion Red HE-3B,
making possible a direct visualization of the microspheres.” Id. at 6.
“The polymers may preferably be coated with agents which promote
cell adhesion. Living cells may also attach to the microspheres forming
layered cells therein which link with surrounding tissues to enhance long
term stability of the beads.” Id. at 5.
The Examiner finds that “Vogel does not specifically teach a coating
comprising poly[bis(2,2,2-trifluoroethoxy)]phosphazene.” Id. at 6. The
Examiner finds that Grunze teaches coating an article such as a medical
device with polyphosphazene derivatives, and preferably poly(2,2,2-
trifluoroethoxy)phosphazene. Id. at 6, 8. The coating is disclosed to improve
the biocompatibility of the devices and prevent or reduce inflammation or
auto-immune reactions. Id. at 7. The coating is also disclosed to promote the

2 US 2003/0211165 A1; Nov. 13, 2003.
3 US 2003/0099683 A1; May 29, 2003.
4 Office Action mailed April 30, 2018.
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adhesion and/or proliferation of cells on the surface of the medical device.
Id. at 8.
The Examiner concludes that it would have been obvious “to provide
poly[bis(trifluorethoxy)phosphazene] as a coating on the embolic hydrogel
microspheres of Vogel” because (a) “Vogel teaches that his microspheres
are desirably coated with a cell adhesion promoter, and Grunze teaches that
his polymer exhibits adhesion and/or proliferation of specific eukaryotic
cells on the surface of a medical device,” and (b) the polymer provides
“bacterial resistance and reduc[es] inflammatory response.” Id. at 9. The
Examiner finds that a skilled artisan would have had a reasonable
expectation of success “because Grunze teaches that there is no particular
limitation on the medical device or the article used as the substrate for the
coating according to the invention and it can be any material, including
polymer.” Id.
We agree with the Examiner that the cited references would have
made obvious the method of claim 13. Vogel discloses “methods . . . for
embolizing a blood vessel, comprising administering to the vessel of a
patient in need thereof a therapeutically effective amount of a bioactive
therapeutic factor, such that the blood vessel is effectively occluded.” Vogel
¶ 41.
Vogel states that “[f]or the drug delivery aspect of [its] invention, the
preferred polymeric material is the microsphere.” Id. ¶ 96. “The
microspheres . . . comprise elastomers, preferably . . . those of the acrylic
family such as polyacrylamides and their derivatives, polyacrylates and their
derivatives as well as polyallyl and polyvinyl compounds.” Id. ¶ 98. The
Examiner finds that this disclosure describes hydrogels. Final Action 5.
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Appellant does not dispute this finding. See, e.g., Appeal Br. 9 (noting that
Vogel describes “high water absorbing” polymers).
Another embodiment of [Vogel’s] invention is to have the
microsphere visible in the light and within the body. For
example, it is also possible to mark the microspheres . . . by
grafting of fluorescent markers derivatives. . . . The
functionalized monomer is generally obtained by chemical
coupling of the monomer with a marker, which can be: a
chemical dye, such as Cibacron Blue or Procion Red HE-3B,
making possible a direct visualization of the microspheres.
Id. ¶ 113.
Vogel states that “[t]he polymers may preferably be coated with
agents which promote cell adhesion. Living cells may also attach to the
microspheres forming layered cells therein which link with surrounding
tissues to enhance long term stability of the beads.” Id. ¶ 97. Vogel states
that “[v]arious types of cell adhesion promoters well known in the art may
be used. . . . . In particular, cell adhesion promoters can be selected from
collagen, gelatin, glucosaminoglycans, fibronectins, lectins, polycations
(such [as] polylysine, chitosan and the like), or any other natural or synthetic
biological cell adhesion agent.” Id. ¶ 114.
Grunze discloses “polyphosphazene derivatives and their use, having
excellent biocompatible properties and imparting bacterial resistance to a
coating of an article such as a medical device.” Grunze ¶ 1. “The alkyl
groups in the [polyphosphazene] . . . can, for example, be substituted with at
least one halogen atom, such as a fluorine atom.” Id. ¶ 19. “The 2,2,2-
trifluoroethoxy group is particularly preferred.” Id. ¶ 20.
Grunze states that
[t]he coating can be applied to any article. The term ‘article’
encompasses any article without any particular limitation of the
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form or shape, but with the need of asepsis or bacterial
resistance. Examples of said article, but not limited to, include
walls and furniture in hospitals, and, in a preferred
embodiment, medical devices.
Id. ¶ 14. “The term ‘medical devices’ encompasses any medically useable
device, particularly devices which come into direct contact with tissue
and/or body fluids of a patient.” Id. ¶ 15.
Grunze states that the “polymer imparts not only biocompatibility to a
coating for e.g. medical devices, but also anti-thrombogenic properties and
bacterial resistance. Thus, substantially no thrombus formation, no
autoimmune response and no inflammatory response of medical devices can
be observed upon application to a patient.” Id. ¶ 16. Grunze states that “the
medical device having the biocompatible coating exhibits surprisingly the
adhesion and/or proliferation of specific eukaryotic cells on the surface of
said medical device. For example, the medical device used as an artificial
blood vessel shows the adhesion and growth of endothelial cells.” Id. ¶ 29.
In view of these teachings, it would have been obvious to modify the
microspheres disclosed by Vogel to include Grunze’s poly(2,2,2-
trifluoroethoxy)phosphazene coating, because Vogel discloses that its
microspheres are preferably coated with an agent that promotes cell
adhesion and Grunze discloses that a medical device coated with its
poly(2,2,2-trifluoroethoxy)phosphazene coating exhibits adhesion and
proliferation of specific cells on its surface, including adhesion and growth
of endothelial cells on an artificial blood vessel. Thus, a skilled artisan
would have reasonably expected that Grunze’s coating would “enhance long
term stability of the beads,” as desired by Vogel. Vogel ¶ 97.
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Appellant argues that
Grunze does not pertain to injectable particles, much less
injectable particles that are capable of efficiently delivering
bioactive therapeutic factors for use in embolization drug
therapy. Instead, Grunze pertains to medical devices with
polyphosphazene coatings . . . as well as other applications,
including coatings for walls and furniture in hospitals. . . . Thus,
Grunze neither discloses nor suggests the use of such coatings
on injectable particles or in connection with bioactive agent
delivery.
Appeal Br. 6–7. Similarly, Appellant argues that Grunze’s disclosure that
“the substrate can be formed from essentially any material[] is hardly a
disclosure or suggestion that the coating can [be] applied to hydrogel
particles.” Id. at 7.
This argument is not persuasive. Grunze discloses that its coating is
broadly applicable, and can be applied to “any article . . . with the need for
aesepsis or bacterial resistance.” Grunze ¶ 14. Among the exemplary
medical devices disclosed by Grunze are those that, like Vogel’s
microspheres, are intended to permanently reside in the vascular system:
artificial blood vessels, cardiovascular stents, and cardiovascular grafts. Id.
¶ 15. Grunze also discloses that “the medical device or the article used as the
substrate for the coating . . . can be any material.” Id. ¶ 24. Appellant has
pointed to no evidence showing that a skilled artisan would have had reason
to consider Grunze’s coating to be inapplicable to Vogel’s microspheres.
Appellant also argues that Vogel discloses its cell adhesion promoter
can be “any other natural or synthetic biological cell adhesion agent.”
Appeal Br. 8. Appellant argues that “biological cell adhesion agents are far
removed from the poly[bis(trifluorethoxy) phosphazene] fluoropolymer that
is described in Grunze, which is not biological, and, unlike the biological
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cell adhesion agents described in Vogel (i.e., proteins and polysaccharides)
is highly hydrophobic.” Id.
This argument is also unpersuasive. While Vogel only expressly
suggests biological cell adhesion agents for use with its microspheres, “[t]he
test for obviousness is what the combined teachings of the references would
have suggested to one of ordinary skill in the art.” In re Young, 927 F.2d
588, 591 (Fed. Cir. 1991). Here, as discussed above, Grunze discloses that
its coating promotes cell adhesion, including adhesion of endothelial cells to
artificial blood vessels. Thus, we agree with the Examiner that Grunze’s
poly(trifluoroethoxy)phosphazene coating would be expected to “act as a
functionally equivalent polymer meeting the functional requirement of
promoting or enhancing the adhesiveness of cells to the surface of the
microspheres desired by Vogel.” Ans. 6.
Appellant argues that “one of ordinary skill in the art would not,
absent the hindsight obtained from the present disclosure, have provided a
hydrophobic poly[bis(trifluorethoxy)phosphazene] coating on the
hydrophilic hydrogel microspheres of Vogel.” Appeal Br. 9. Appellant
argues that “the high hydrophobicity of the poly[bis(trifluorethoxy)
phosphazene] of Grunze would transform the hydrophilic nature of surfaces
of the particles of Vogel, and thus also the properties arising from such
hydrophilic nature (e.g., suspendability, swellability, etc.).” Id. at 10.5
Similarly, Appellant argues that, “in view of [the] extremes in composition
between the hydrophilic hydrogel microspheres of Vogel and the highly

5 Appellant also argues that the references would not have been combined
because Grunze does not suggest using its coating on injectable particles like
those of Vogel. Appeal Br. 9–10. This argument has already been addressed.
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hydrophobic fluoropolymer coating of Grunze, there would not be a
reasonable expectation of success in coating the hydrophilic hydrogel
microspheres with the highly hydrophobic fluoropolymer.” Id. at 10–11.
This argument is unpersuasive. As the Examiner has pointed out
(Ans. 7), Vogel expressly discloses that the hydrophobicity of its
microspheres can be modified. Vogel states that “the hydrophobicity or ionic
character of the embolic material can be modified as deemed necessary.”
Vogel ¶ 111. Thus, although Vogel states that “[t]he preferred polymeric
material is based on substantially spherical, substantially hydrophilic, inert,
ionic and cross-linked polymers,” id. ¶ 31, its disclosure that the
hydrophobicity of the embolic material can be modified would lead a skilled
artisan to expect the microspheres to be useful even with the addition of a
hydrophobic component such as Grunze’s coating, especially in view of
Grunze’s suggestion of using its poly(trifluoroethoxy)phosphazene material
in implanted medical devices. Appellant has not pointed to evidence
showing that Vogel’s microspheres would not have been expected to
function as embolic material if coated with Grunze’s polymer.
Finally, Appellant argues that
resistance to bacterial adhesion, while of significance with
regard to implanted devices, particularly for urological devices
(see paragraph [0048]), there is no disclosure or suggestion in
Vogel or Grunze that methods of embolization, where sterile
and pyrogenic (pyrogen-free) solutions are injected into the
patient (see paragraph [0109] of Vogel), are prone to such
bacterial contamination.
Appeal Br. 11.
This argument is also unpersuasive. Vogel suggests coating its
microspheres with a cell adhesion promoter. Vogel ¶ 97. Grunze discloses
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that its poly(trifluoroethoxy)phosphazene coating promotes cell adhesion.
Grunze ¶ 29. These disclosures would have provided adequate reason for a
skilled artisan to combine Grunze’s coating with Vogel’s microspheres,
regardless of any desire to reduce bacterial contamination of the
microspheres.
For the reasons discussed above, we affirm the rejection of claim 13
under 35 U.S.C. § 103(a) based on Vogel and Grunze. Claims 15 and 34–48
fall with claim 13 because they were not argued separately. 37 C.F.R.
§ 41.37(c)(1)(iv).
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed
13, 15, 34–48 103(a) Vogel, Grunze 13, 15, 34–48

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