Pathologica LLC

Patent Trials and Appeals Board

Feb 21, 2020

15583697 - (D) (P.T.A.B. Feb. 21, 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.
15/583,697 05/01/2017 John MCKEARN PATH0014-201C2-US 7683
80117 7590 02/21/2020
GLOBAL PATENT GROUP - PATH
2275 Cassens Drive
SUITE 118
ST. LOUIS, MO 63026
EXAMINER
VANHORN, ABIGAIL LOUISE
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
02/21/2020 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):
admin@globalpatentgroup.com
lwilson@globalpatentgroup.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JOHN MCKEARN and JEREMY BLITZER
____________

Appeal 2019-006376
Application 15/583,697
Technology Center 1600
____________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
ELIZABETH A. LAVIER, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 25–36 (see Appeal Br. 3). 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 “Pathologica
LLC” (Appellant’s April 22, 2019 Appeal Brief (Appeal Br.) 3).
Appeal 2019-006376
Application 15/583,697

2
STATEMENT OF THE CASE
Appellant’s disclosure relates to “controlled-release oral
pharmaceutical dosage forms comprising [methylglyoxal
bis(guanylhydrazone) (MGBG)] . . . and their application for the improved
treatment of diseases with reduced side effects” (Spec.2 ¶ 3). Appellant’s
claim 25 is reproduced below:
25. A method of treating inflammation or an inflammatory
condition, comprising the administration, to a patient in need
thereof, a delayed-release oral pharmaceutical dosage form
comprising methylglyoxal bis(guanylhydrazone) (MGBG) and
an enteric coating.
(Appeal Br. 25.)

Grounds of rejection before this Panel for review:
Claims 25–30, 35, and 36 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Hadlock,3 Knight,4 and Allen.5
Claims 25–36 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Hadlock, Knight, Allen, and Khan.6

2 Appellant’s May 1, 2017 Specification.
3 Hadlock et al., US 2008/0262092 A1, published Oct. 23, 2008.
4 Knight, III, US 4,520,031, issued May 28, 1985.
5 Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems 8th ed.,
260, 262, and 268–271 (Loyd V. Allen, Jr., PhD, et al., eds., LIPPINCOTT
WILLIAMS & WILKINS) (1995).
6 M. Zahirul I. Khan et al., A pH-dependent colon targeted oral drug
delivery system using methacrylic acid copolymers I. Manipulation of drug
release using Eudragit® L100-55 and Eudragit® S100 combinations, 58
JOURNAL OF CONTROLLED RELEASE 215–222 (1999).
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Application 15/583,697

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ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Hadlock discloses “methods for the regulation of osteopontin
activity in a subject as well as for treating or preventing conditions
associated with an increased activity of osteopontin activity in a subject”
(Hadlock, Abstract; see id. ¶ 2 (“Osteopontin (‘OPN’), also known as
secreted phosphoprotein 1 (‘SPP1’), early T-lymphocyte activation marker
(‘Eta-1’), sialoprotein I or 44K BPP (bone phosphoprotein), is a
glycosylated phosphoprotein found in plasma, other bodily fluids, and
extracellular matrices.”)).
FF 2. Hadlock discloses that “[o]steopontin is associated with, and plays a
role in, the regulation and progression of many diseases,” including
“autoimmune disorders and is overexpressed in a variety of cancers”
(Hadlock ¶ 4; see generally id. ¶ 33 (disclosing “conditions associated with
an increased activity of osteopontin”)).
FF 3. Hadlock discloses that an “agent useful in the methods of the
invention can be any agent that decreases the activity of osteopontin”
(Hadlock ¶ 39; see also id. ¶ 41 (Hadlock discloses that “[t]he agent can be
any kind of known or later discovered agent that can inhibit the activity of
the enzyme S-adenosyl methionine decarboxylase, can inhibit polyamine
biosynthesis, or that can increase the activity of adenosine in, for example, a
cell”); see also Hadlock, Table 1 (listing exemplary inhibitors of S-adenosyl
methionine decarboxylase and/or polyamine biosynthesis)).
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FF 4. Hadlock discloses that agents within the scope of its disclosure can
be formulated using art recognized excipients and carriers and “may be
administered via any conventional route,” including “oral routes” in the form
of a “liquid, powder, suspensions, tablets, pills, capsules, sprays and
aerosols” (Hadlock ¶ 88; see generally Final Act. 7 4).
FF 5. Hadlock discloses:
The optimal dose, frequency of administration, and duration of
treatment with the agent that decreases the activity of
osteopontin in a subject may vary from subject to subject,
depending on the subject’s condition, the subject’s age, weight,
response to the treatment, and the nature of the therapeutic
entity. The optimal dose and duration of treatment may be best
determined by monitoring the subject’s response during the
course of the treatment. In some instances, the administration
of higher doses may permit less frequent administration, and
lower doses may require more frequent administration in order
to achieve a clinically significant improvement in the subject's
condition. The agent may be administered as a single dose or in
multiple doses.
(Hadlock ¶ 85.)
FF 6. Hadlock discloses that an agent within the scope of its invention may
be MGBG (see Hadlock ¶ 80; see also id. at Table 1; cf. id. ¶ 81 (Hadlock
discloses that “the agent is a compound selected from the list of agents listed
in Table 1, with the provision that the agent is not MGBG” (emphasis
added))).
FF 7. Hadlock discloses a method of treating or preventing, inter alia, an
inflammatory condition, comprising the administration of an effective
amount of MGBG or a salt thereof to a subject in need of such treatment
(see, e.g., Hadlock 23 (claim 13); see also Final Act. 4).

7 Examiner’s June 28, 2018 Final Office Action.
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FF 8. Examiner finds that Hadlock fails to disclose “a delayed release
dosage form” of MGBG (Final Act. 5).
FF 9. Knight “relates to a method of treating cancer or advanced malignant
disease with . . . [MGBG]” (Knight 1: 14–16).
FF 10. Knight discloses that the clinical effectiveness of MGBG is
“severely restrained by the occurrence of concomitant profound and protean
toxicity associated with its administration” (Knight 1: 27–2: 12; see also id.
at 6: 60–10: 7; see generally Final Act. 5 (Examiner appreciates the
“toxicological effects” associated with MGBG administration, including
“gastrointestinal toxicity, delayed and fatal hypoglycemia, hepatic and renal
damage, bone marrow depression, diarrhea and phlebitis”).
FF 11. Knight discloses that the “toxicological effects observed clinically
[with MGBG administration] have been attributed to cumulative effects of
repeated daily doses” and reported that “clinical investigations confirm the
desired objectives that MGBG administered at weekly intervals is an
effective chemotherapeutic agent which produces significant improvement
in various cancer pathologies while exhibiting a higher therapeutic index
than that previously documented concerning a daily dosing schedule”
(Knight 2: 17–19; see also id. at 10: 11–17; Final Act. 5 (Examiner finds
that Knight disclosed that “[t]he toxic effects [of MGBG administration]
have been attributed to cumulative effects of repeated daily doses” and
provided a “method for reducing toxic effects of . . . [MGBG
administration]”)).
FF 12. Examiner relies on Allen to disclose “modified release dosage forms
and drug delivery systems,” such as enterically coated oral formulations,
which, inter alia, “reduce gastric distress caused by drugs particularly
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irritating to the stomach” (see Final Act. 5–6 (citing Allen 262, 268, and
271)).
FF 13. Examiner finds that the combination of Hadlock, Knight, and Allen
fails to suggest “an enteric coating comprising a methacrylic acid/ethyl
acrylate copolymer” and relies on Khan to make up for that deficiency in the
combination of Hadlock, Knight, and Allen (see Final Act. 7 (citing Khan
216 and 222)).
ANALYSIS
The rejection over the combination of Hadlock, Knight, and Allen:
Based on the combination of Hadlock, Knight, and Allen, Examiner
concludes that, at the time Appellant’s invention was made, it would have
been prima facie obvious to orally administer an enterically coated MGBG
formulation to a patient in need of treating inflammation to “reduce gastric
distress,” because “MGBG is known to have gastric side effects such as
nausea and vomiting (emesis) as taught by Knight” (Final Act. 6). We are
not persuaded.
As Appellant explains, “Hadlock mentions oral administration only
once, in a generic paragraph stating that ‘agents’––that is SAMDC inhibitors
in general, not MGBG in particular––may be administered by nearly any
conceivable route, including orally” and “gives no indication of how MGBG
may be administered orally with any reasonable expectation of success”
(Appeal Br. 13; see FF 3–4). This is an important observation, because
Knight, as relied upon by Examiner, discloses the “toxicological effects”
associated with MGBG administration (see FF 10). In this regard, Knight
discloses that the toxic effect of MGBG administration is a cumulative
effect, not limited to gastrointestinal toxicity, and that the toxic effect may
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be addressed by modifying the MGBG dosing schedule from daily to weekly
dosing (see FF 11). We recognize Examiner’s reliance on Allen to suggest
that oral drug formulations may be provided with enteric coatings to reduce
gastric distress caused by drugs particularly irritating to the stomach (FF 12).
Examiner, however, fails to identify an evidentiary basis on this record to
support a conclusion that MGBG’s art recognized toxicity is a result of
stomach irritation or the formulation of particular dosages, which may be
overcome with an enteric coating. To the contrary, the art relied upon by
Examiner supports a conclusion that MGBG toxicity, which is not limited to
gastrointestinal toxicity, relates to the cumulative effect of repeated daily
MGBG dosing, and may be alleviated by a reduction in dosing frequency
(see FF 10). Stated differently, Examiner failed to provide an evidentiary
basis on this record to support a conclusion that a person of ordinary skill in
this art would have reasonably expected an enteric coating would exhibit any
effect on MGBG’s toxicity.
Obviousness requires more than a mere showing that the prior
art includes separate references covering each separate
limitation in a claim under examination. KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 418, 127 S.Ct. 1727, 167 L.Ed.2d
705 (2007). Rather, obviousness requires the additional
showing that a person of ordinary skill at the time of the
invention would have selected and combined those prior art
elements in the normal course of research and development to
yield the claimed invention. Id. at 421, 127 S.Ct. 1727.
Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011).

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Application 15/583,697

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The rejection over the combination of Hadlock, Knight, Allen and Khan:
Based on the combination of Hadlock, Knight, and Allen, Examiner
concludes that, at the time Appellant’s invention was made, it would have
been prima facie obvious to “utilize a methacrylic acid/ethyl acrylate
copolymer . . . in an enteric coating” (Final Act. 8). We are not persuaded.
Examiner failed to establish that Khan makes up for the deficiencies
in the combination of Hadlock, Knight, and Allen discussed above.
CONCLUSION
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness.
The rejection of claims 25–30, 35, and 36 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Hadlock, Knight, and Allen is
reversed.
The rejection of claims 25–36 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Hadlock, Knight, Allen, and Khan is
reversed.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
25–30, 35, 36 103 Hadlock, Knight,
Allen
25–30, 35,
36
25–36 103 Hadlock, Knight,
Allen, Khan
25–36
Overall
Outcome
25–36

REVERSED