Kirk P. Seward

Patent Trials and Appeals Board

May 14, 2020

2018008779 (P.T.A.B. May. 14, 2020)

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.
13/656,413 10/19/2012 Kirk P. SEWARD 34634-726.201 1023
21971 7590 05/14/2020
WILSON, SONSINI, GOODRICH & ROSATI
650 PAGE MILL ROAD
PALO ALTO, CA 94304-1050
EXAMINER
PHAN, DOAN THI-THUC
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
05/14/2020 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):
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PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte KIRK P. SEWARD

Appeal 2018-008779
Application 13/656,413
Technology Center 1600
____________

Before ULRIKE W. JENKS, TAWEN CHANG, and JAMIE WISZ,
Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims directed to a method of modulating local tissue
physiology as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

1 Appellant identifies the real party in interest as Mercator Medsystems, Inc.
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
According to the Specification, it was known “that pH differences
may alter drug effects in cell culture assays, the localized or regionalized
modification of pH within the body to enable more rapid drug uptake, more
rapid clearance, or improved effect has not been attempted.” Spec. ¶ 3. The
Specification describes methods for “the modulation of local tonicity or
osmolarity [in the body] to achieve enhanced cellular uptake of
pharmaceutical agents in formulation with or delivered before or after the
agents that modulate local tonicity or osmolarity.” Id. ¶ 14.
Claims 17, 20, 21, 24, and 59–77 are on appeal, and can be found in
the Claims Appendix of the Appeal Brief. Claim 17 is representative of the
claims on appeal, and reads as follows:
17. A method for modulating local tissue physiology comprising:
injecting a preparation comprising a liquid, gel, or
semisolid into the tissue of a perivascular space beyond an
external elastic lamina of a blood vessel;
buffering the local tissue physiology by raising or lowering
the pH of the local tissue with the injected preparation,
wherein the preparation comprises a therapeutic agent
that has its index effect at a physiological condition modulated
by the injection of such preparation, but not having an index
effect at a neutral physiological condition; and
enhancing uptake of the therapeutic agent by the local
tissue by the raising or lowering of the pH of the local tissue.
Appeal Br. 14 (Claims Appendix) (emphasis added).
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REFERENCE(S)
The prior art relied upon by Examiner is:
Name Reference Date
Rosenthal et al.
(“Rosenthal”)
US 6,524,274 B1 Feb. 25, 2003
Goodson et al.
(“Goodson”)
US 2005/0267010 A1 Dec. 1, 2005
Seward et al. (“Seward”) US 2007/0100318 A1 May 3, 2007
Vyavahare et al.
(“Vyavahare”)
US 2007/0281026 A1 Dec. 6, 2007
Blaskovich et al.
(“Blaskovich”)
US 2011/0091549 A1 Apr. 21, 2011
REJECTION(S)
The claims stand rejected as follows:
I. Claims 17, 20, 21, 24, 61, 63–67, and 70–77 under pre-AIA
35 U.S.C. § 103(a) as being unpatentable over Rosenthal,
Vyavahare, and Seward.
II. Claims 21, 24, 59, and 60 under pre-AIA 35 U.S.C. § 103(a) as
being unpatentable over Rosenthal, Vyavahare, Seward, and
Blaskovich.
III. Claims 62, 68, and 69 under pre-AIA 35 U.S.C. § 103(a) as
being unpatentable over Rosenthal, Vyavahare, Seward, and
Goodson.

I. Obviousness over Rosenthal, Vyavahare, and Seward
Does the preponderance of evidence of record relied upon by
Examiner supports the conclusion of obviousness?
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A. Findings of Fact (FF)
FF1 Rosenthal teaches delivering a drug associated with a
hydrogel to a desired location. Rosenthal Abstract; see id. at
1:62–2:10. Rosenthal teaches maneuvering “a catheter
constructed for insertion in the body, a portion of which carries
a hydrogel having the capacity to incorporate a predetermined
substantial amount of a drug,” to the point of desired drug
application. Id. at 1:51–55.
FF2 Rosenthal teaches that the drug is “immobilized in the
hydrogel until released by a triggering agent or condition which
is different from ambient physiological conditions.” Id. at 2:2–
4; see also id. at 2:43–44 (“the drug released by a change in
pH”); see also id. at 3:35–39 (“The immobilized drug to be
delivered to a body tissue may also be released from the
hydrogel by contacting the hydrogel with a solution having a
pH which induces a volume phase transition of hydrogel.”); see
also id. at 6:42–43 (“Contact of the triggering agent with the
hydrogel 55 induces the release of drug carried by the
hydrogel.”); see also id. at 8:59–62 (“Upon contact with a
triggering agent, the hydrogel reacts, e.g., swells or contracts,
such that the drug is delivered to the desired body tissue in a
burst or over a desired time frame.”).
FF3 Vyavahare teaches the use of hydrogels for the sustained
delivery of drugs. Vyavahare ¶¶ 10, 52. Vyavahare teaches that
“the disclosed compounds can be delivered to the connective
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Application 13/656,413
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tissue of a blood vessel wall via intravenous delivery.” Id. ¶ 11,
see id. ¶ 56.
FF4 Vyavahare teaches that the hydrogels can polymerize via
self-assembly, or they can be induced to polymerize by any
known method, such as for example by the presence of an
initiator. Id. ¶ 63. “[T]he hydrogel can self-assemble upon
contact of the various components or upon contact in
conjunction with the presence of particular environmental
conditions (such as temperature or pH).” Id.
FF5 Seward teaches that “[t]he perivascular region is defined
as the region beyond external elastic lamina of an artery or
beyond the tunica media of a vein.” Seward ¶ 16, see also id.
¶ 41 (“[T]he perivascular space will be considered anything
lying beyond the external elastic lamina EEL, including regions
within the adventitia and beyond.”). Seward teaches delivering
“pharmaceutical agents to the adventitia surrounding a blood
vessel utilize a catheter having a microneedle.” Id. Abstract, see
id. ¶¶ 14, 40, 41.
FF6 Examiner finds that
the trigger solution [of Rosenthal] intrinsically modulate
the local tissue physiology by raising or lowering the pH
of the local tissue (for example: if sodium bicarbonate is
used as the triggering solution, the sodium bicarbonate
will raise the pH of the local tissue above 7.5 because
sodium bicarbonate is an alkaline), the raising or lowering
of the pH of the local tissue would lead to enhancing the
uptake of the drug by the local tissue.
Final Act. 11–12; Ans. 20; see id. at 6.

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B. Analysis
Based on the combination of Rosenthal, Vyavahare, and Seward,
Examiner concludes that, at the time Appellant’s invention was made, it
would have been prima facie obvious to formulate a drug into a hydrogel
and release the drug in the perivascular tissue environment. See Final Act.
3–8, 11–12; see Ans. 4–13, 20; see FF1–FF5. Examiner acknowledges that
Rosenthal alone does not teach injecting a composition into the tissue of the
perivascular space, or injecting the composition beyond an external elastic
lamina of a blood vessel and therefore looks to Vyavahare and Seward for
teaching these elements. See Final Act. 6; see Ans. 8. Examiner, therefore, is
relying on Rosenthal for teaching the claimed preparation comprising a
therapeutic agent, wherein the preparation can modulate local tissue
physiology by raising and lowering the pH level. See Final Act. 11–12; see
Ans. 20; FF6.
Appellant contends that combination of references “does not teach or
reasonably suggest the step of ‘buffering the local tissue physiology by
raising or lowering the pH of the local tissue with the injected preparation’
as recited by claim 17.” Appeal Br. 8; see also Reply Br. 4 (“[T]he
Rosenthal [reference teaches that] (i) hydrogel immobilized with drug and
(ii) the triggering agent introduced into the space between the coating and
the housing seem to be two separate elements rather than a ‘single
composite.’”).
On this record, we find that Appellant has the better position. “[T]he
[E]xaminer bears the initial burden, on review of the prior art or on any other
ground, of presenting a prima facie case of unpatentability.” In re Oetiker,
977 F.2d 1443, 1445 (Fed. Cir. 1992).
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We agree with Appellant that the claim as written requires a
“preparation” that not only modulates the pH at the local tissue level but also
contains a drug of interest. See Appeal Br. 8; see Reply Br. 4. Examiner,
however, has not identified such a preparation in the combined references.
Indeed, Examiner relies on a triggering solution to release the drug from the
hydrogel disclosed in Rosenthal, and in addition relies on this triggering
solution as altering the pH at the local tissue level. FF6. We find that
Examiner has not identified a preparation that both holds the drug and alters
the pH at the local tissue level as recited in the claim.
Examiner in the Answer tries to rectify this shortcoming by
identifying a “preparation” as encompassing “the balloon catheter that
contained the hydrogel immobilized drug and the triggering agent is a single
composite.” Ans. 23. We agree with Appellant, and find that Examiner
interpretation of “a preparation comprising a liquid, gel, or semisolid” as
encompassing a catheter containing a gel and liquid is unreasonable. We
note that the claim language reciting the conjunction “or” indicates that the
selection is between the three listed options, and not a combination of these
options. We do not discern, and Examiner has not directed us to, any
disclosure in the Specification that would indicate such an interpretation is
necessary. Accordingly, we are not persuaded by Examiner’s interpretation
in the Answer that a “preparation” reasonably encompasses a catheter and a
combination of a liquid triggering solution and a gel containing a drug.
On this record, Examiner failed to meet the initial burden of
presenting a prima facie case of unpatentability. In re Oetiker, 977 F.2d at
1445. Accordingly, we are compelled to reverse the rejection of record.
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C. Conclusion
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness. The rejection of claims 17, 20, 21, 24,
61, 63–67, and 70–77 under 35 U.S.C. § 103(a) as unpatentable over the
combination of Rosenthal, Vyavahare, and Seward is reversed.

II. Obviousness over Rosenthal, Vyavahare, Seward, and Blaskovich
The rejection of claims 21, 24, 59, and 60 relies upon the underlying
rejection of claim 17, where Blaskovich is relied upon to teach an alkaline
hydrogel and the use of a contrast medium. See Ans. 13. Because this
rejection does not address the underlying issue with respect to claim 17 as
discussed above (see I.B), the combination with Blaskovich still fails to
teach a preparation that both holds a drug of interest and modulates the pH
of the local tissue environment. Therefore, having reversed the underlying
rejection over Rosenthal, Vyavahare, and Seward, we also reverse this
rejection for the same reasons.

III. Obviousness over Rosenthal, Vyavahare, Seward, and Goodson
The rejection of claims 62, 68, and 69 relies upon the underlying
rejection of claim 17, where Goodson is relied upon to address the additional
claim element that the generated plume diffuses to reach local tissue. See
Ans. 16 (“Rosenthal, Vyavahare and Seward do not expressly teach the
limitations of claims 62, 68 and 69 of the instant invention.”). Because this
rejection does not address the underlying issue with respect to claim 17 as
discussed above (see I.B), the combination with Goodson still fails to teach a
preparation that both holds a drug of interest and modulates the pH of the
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local tissue environment. Therefore, having reversed the underlying
rejection over Rosenthal, Vyavahare, and Seward, we also reverse this
rejection for the same reasons.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
17, 20, 21,
24, 61,
63−67,
70−77
103(a) Rosenthal,
Vyavahare, Seward
17, 20, 21,
24, 61,
63−67,
70−77
21, 24, 59,
60
103(a) Rosenthal,
Vyavahare,
Seward,
Blaskovich
21, 24, 59,
60
62, 68, 69 103(a) Rosenthal,
Vyavahare,
Seward, Goodson
62, 68, 69
Overall
Outcome
17, 20, 21,
24, 59–77

REVERSED