Ex Parte Schäffler

Patent Trial and Appeal Board

Aug 30, 2017

14305165 (P.T.A.B. Aug. 30, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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P.O.Box 1450
Alexandria, Virginia 22313-1450
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/305,165 06/16/2014 Achim Schaffler HOR0017-201C2-US 8753
101325 7590 09/01/2017
GT ORAT PATFNT GROUP - HOR
EXAMINER
17014 NEW COLLEGE AVENUE CORNET, JEAN P
SUITE 201
ST. LOUIS, MO 63040 ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
09/01/2017 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ACHIM SCHAFFLER
Appeal 2017-003 5971
Application 14/305,165
Technology Center 1600
Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to a method of administering
prednisone to a patient having rheumatoid arthritis. The Examiner rejected
the claims under 35 U.S.C. § 103 as obvious. We have jurisdiction under 35
U.S.C. § 6(b). The § 103 rejections are affirmed.
1 The Appeal Brief (“Appeal Br.”) 3 lists Horizon Pharma Switzerland
GmbH as the real-party-in-interest.
Appeal 2017-003597
Application 14/305,165
STATEMENT OF THE CASE
Claim 48—56 stand rejected by the Examiner as follows (see Final
Office Action, dated Nov. 5, 2015 (“Final Act.”)):
Rejection 1. Claims 48, 50, 51, and 54—56 under pre-AIA 35 U.S.C.
§ 103(a) as obvious in view of US Publ. Pat. App. 2007/0110807 Al, publ.
May 17, 2007 (“Vergnault”); T. Sokka, Assessment of Pain in Rheumatic
Diseases, Clin. Exp. Rheumatol. (Suppl. 39):S77—S84, 2005 (“Sokka”);
Sterapred product specification, Nov. 2003 (“Sterapred”); and David
Gotlieb, DMARDs in Rheumatoid Arthritis, Oct. 1999 (“Gotlieb”). Final
Act. 3.
Rejection 2. Claim 49 under pre-AIA 35 U.S.C. § 103(a) as obvious
in view of Vergnault, Sokka, Sterapred, Gotlieb, and Bjorn Svensson et al.,
Low-Dose Prednisolone in Addition to the Initial Disease-Modifying
Antirheumatic Drug in Patients With Early Active Rheumatoid Arthritis
Reduces Joint Destruction and Increases the Remission Rate, A Two-Year
Randomized Trial, Arthritis & Rheumatism, 52(1):3360—3370, 2005
(“Svensson”). Final Act. 7.
Rejection 3. Claims 52 and 53 under pre-AIA 35 U.S.C. § 103(a) as
obvious in view of Vergnault, Sokka, Sterapred, Gotlieb, and Lenore M.
Buckley et al.. Effects of Low Dose Corticosteroids on the Bone Mineral
Density of Patients with Rheumatoid Arthritis, J. Rheumatol., 22: 1055—
1059, 1995 (“Buckley”). Final Act. 9.
Claim 48, the only independent claim on appeal, is reproduced below.
Claims limitations have been numbered [1]—[7] for reference and
indentations have been added for clarity.
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Application 14/305,165
48. A method of administering prednisone to a patient having
rheumatoid arthritis with a
[1] pain level of >50-70 mm on a 100 mm self reported
visual analogue scale for pain and
[2] an incomplete clinical response after prior treatment
with disease-modifying antirheumatic drug (DMARD) therapy
alone comprising
[3] administering an oral dosage form comprising an
initial dosage of 1, 2, 5, or 10 mg of prednisone, to the patient
once daily at or before bedtime, wherein the oral dosage form is
administered with food,
[4] determining the patient’s clinical response to said
administration, and
[5] if said patient has a satisfactory clinical response, the
method further comprises administering a maintenance dosage
that is less than the initial dosage until a dosage of prednisone
which will maintain a satisfactory clinical response is reached, or
[6] if said patient does not have a satisfactory clinical
response, the method further comprises administering an
increased dosage that is more than the initial dosage until a
satisfactory clinical response is determined,
[7] wherein release of the prednisone from the oral dosage
form is delayed for a time period (tlag) of 2-10 hours after
administration of the oral dosage form.
REJECTIONS 1 AND 2
The following findings of fact (“FF”) are based on the Examiner’s
obviousness rejection as set forth in the Final Office Action.
The preamble of claim 48 requires administering prednisone to a
patient having RA who has experienced [1] a specific pain level and [2] an
incomplete response to DMARD therapy.
FF 1. Gotlieb teaches that patients with RA experience joint pain, and
that DMARDS are administered early to treat such pain (“DMARDS should
be used before development of erosive disease or deformities develop.
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Therapy must be initiated if the pain and synovitis persists and especially if
function is compromised.” Gotlieb 1.)
FF2. Gotlieb further teaches that not all patients respond to DMARD
(“Approximately 2/3 of patients will respond to DMARDS . . . Id. at 3.).
FF3. Gotlieb also teaches that “[t]he main problem with the drugs is
fall-off in efficacy over time.” Id.
FF4. Thus, Gotlieb discloses that patients with RA experience [1]
pain (FF1) — albeit not the specific level recited in claim 48 — and [2] an
incomplete response to DMARDS (FF2, FF3).
FF5. As shown in Gotlieb’s proposed algorithm for RA therapy,
Gotlieb discloses administering prednisone to patients who have an
incomplete response to DMARD therapy as required by limitations [2] and
[3] (Gotlieb 11).
FF6. The diagram of the algorithm in Gotlieb is reproduced below:
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FF7. Under Regimen 1, Gotlieb discloses administering DMARDS
“Sulphasalazine Antimalarials Minocycline” (Gotlieb 2).
FF8. Gotlieb further discloses in the algorithm that, if “No response”
is observed under Regimen 1, “Methotrexate +/- low dose prednisone” is
administered.
FF9. Thus, consistent with Gotlieb’s more general teaching (FF2,
FF3), if an incomplete response to DMARD therapy (“No response”) is
observed (limitation [2] of claim 48), prednisone may be administered (“+/-
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low dose prednisone”) along with methotrexate (a DMARD), meeting
limitation [3] of claim of claim 48 of administering prednisone.
FF10. Svensson teaches that “low-dose prednisolone [7.5 mg] as an
adjunct to DMARDs in early active RA” “retarded the progression of
radiographic damage after 2 years in patients with early RA, provided a high
remission rate, and was well tolerated.” Svensson 3360 (“Conclusion”).
Svensson also teaches the combination was known to reduce signs and
symptoms of RA. Id. at 3361
FF11. Sterapred, the package insert and instructions for administering
prednisone to treat diseases, including RA, teaches limitations [4] and [5] of
the claim of adjusting prednisone dosage depending upon whether a
“satisfactory clinical response” is achieved.
FF12. Sterapred discloses;
The initial dosage of STERAPRED 5 mg, STERAPRED 5 mg
12 DAY, STERAPRED DS, STERAPRED DS 12 DAY
(Prednisone Tablets) may vary from 5 mg to 60 mg of prednisone
per day depending on the specific disease entity being treated. In
situations of less severity lower doses will generally suffice
while in selected patients higher initial doses may be required.
The initial dosage should be maintained or adjusted until a
satisfactory response is noted. If after a reasonable period of time
there is a lack of satisfactory clinical response, prednisone should
be discontinued and the patient transferred to other appropriate
therapy. IT SHOULD BE EMPHASIZED THAT DOSAGE
REQUIREMENTS ARE VARIABLE AND MUST BE
INDIVIDUALIZED ON THE BASIS OF THE DISEASE
UNDER TREATMENT AND THE RESPONSE OF THE
PATIENT. After a favorable response is noted, the proper
maintenance dosage should be determined by decreasing the
initial drug dosage in small decrements at appropriate time
intervals until the lowest dosage which will maintain an adequate
clinical response is reached.
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Sterapred, section titled “DOSAGE AND ADMINISTRATION (emphasis
added).
FF13. As found by the Examiner, the specifically claimed pain level
(limitation [1]) is not described in Gotlieb nor is the claimed time-lag
prednisone (limitation [7]).
FF14. However, Sokka teaches assessing pain on self-reported visual
analogue scale (VAS) in RA patients (“Visual analog pain scalesTable 1.
Sokka S-78, S-80), and discloses one study in which baseline pain of 52 on
the VAS scale was observed, within the claimed range of “>50-70 mm on a
100 mm self-reported visual analogue scale for pain.”
FF15. Gotlieb also teaches using visual analogue score for assessing
pain. Gotlieb 4.
FF16. With respect to the delayed release prednisone, Vergnault
describes a tablet “adapted to provide a lag time of between about 2 to 6
hours during which substantially no drug substance is released” (Vergnault,
Abstract) which falls with the 2—10 hour range recited in claim 48
(limitation [7]).
FF17. Vergnault teaches the advantage of administering prednisone
in its time-lag tablet, providing a reason to administer prednisone at the time
of day recited in claim 48 and in the recited time-lag form:
Notwithstanding the general applicability of the tablets in
relation to a wide range of drug substances, the present invention
is particularly suited to delivery of the glucocorticosteroids
aforementioned, and particularly prednisone, prednisolone and
methylprednisolone. These steroids are useful in the treatment
i.a, of rheumatoid arthritis and joint pain. As already stated, the
symptoms of these conditions appear according to a circadian
rhythm and with great predictability during the early hours of the
morning. Accordingly, the glucocorticosteroids, and in
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particular prednisone are eminently suited for delivery from
tablets according to this invention not only because of their
narrow absorption window, but also because a tablet may be
administered in the evening before bedtime anytime around 8 pm
until midnight, e.g. around 10-12 at night, to deliver maximum
plasma concentration of the drug substance before maximum
secretion of IL-6 (which occur around 2 am to 4 am), thereby
effectively addressing the underlying causes of the morning
symptoms. In this way, these symptoms are more effectively
treated
Id. at 178.
FF18. Vergnault discloses a time-lag tablet comprising 5 mg
prednisone. Id. at 145, Table 1.
DISCUSSION
In beginning their argument as to why the claims are non-obvious,
Appellant identifies specific deficiencies in Vergnault, Sokka, and Sterapred.
Appeal Br. 8—9. These arguments are not persuasive because the rejection is
based on the combination of publications, not one publication alone. “Non­
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). The
references must be read, not in isolation, but in combination for what they
fairly teach as a whole. Id.
Appellant contends that Gotlieb
teaches away from the pending claims by suggesting that the
combinations [of DMARDS] listed above, each of which
contains methotrexate and excludes prednisone, are “superior.”
Thus one of skill in the art, based on the teachings of Gotlieb,
would choose to use one of those combinations with
methotrexate in preference to the use of prednisone.
Appeal Br. 10.
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Appellant further contends that none of the publications cited in the
Examiner’s rejection “provide any rationale for using the prednisone oral
dosage form having delayed release in the particular patient subpopulation
claimed herein.” Id.
Appellant’s arguments do not persuade us that the Examiner erred.
As found by the Examiner, Gotlieb clearly teaches administering
prednisone after no response to a DMARD, which would constitute an
incomplete response to the DMARD. FF2, FF3, FF5—FF9. Thus,
Appellant’s statement that administration of prednisone to the same
subpopulation of patients recited in claim 48 is not taught by Gotlieb is
inconsistent with the express teachings in that publication.
Claim 49 further requires administering a DMARD with the
prednisone. Gotlieb teaches if there is no response to a DMARD, then
another DMARD, methotrexate, is added along with prednisone, meeting the
limitation of the claim. FF8, FF9.
One of ordinary skill in the art would have had further reason to
utilize the combination of DMARD and prednisone in view of the teaching
in Svensson of retarding disease progression and high remission rate by
patients taking both drugs. FF10.
Appellant identifies a table from prescribing information from
RAYOS, “a delayed release dosage form of prednisone falling within the
claims of the subject application, that patient population can be treated
effectively with such a dosage form.” Appeal Br. 10. Appellant states that
the table shows:
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said patients having a baseline assessment of 55.3 on a 100 mm
self-reported visual analogue scale for pain had reduced their
pain substantially to 33.0 after 12 weeks of the use of 5 mg
RAYOS in combination with a DMARD, a reduction of 40%. In
contrast, the reduction was from 50.5 to only 39.6, a reduction of
21 %, for DMARD alone.
Id. 11
A showing of “unexpected results” can be used to demonstrate the
non-obviousness of the claimed invention. In re Soni, 54 F.3d 746, 750
(Fed. Cir. 1995) (“One way for a patent applicant to rebut a prima facie case
of obviousness is to make a showing of ‘unexpected results,’ i.e., to show
that the claimed invention exhibits some superior property or advantage that
a person of ordinary skill in the relevant art would have found surprising or
unexpected.”). Those results must be “surprising or unexpected” to one of
ordinary skill in the art when considered in the context of the closest prior
art. Soni, 54 F.3d at 750.
However, in this case, Appellant has not asserted nor provided
evidence that the results reported in the table were unexpected to one of
ordinary skill in the art. To the contrary, Svensson teaches that the
combination of a DMARD and prednisone led to retarding disease
progression, high remission, and reducing signs and symptoms of RA
(FF10), indicating that the pain levels would also be reduced — a goal of drug
therapy in RA (Gotlieb 1; Sokka S-77, S-79). See Ans. 14. Thus, the
results reported in the table of utilizing a DMARD and prednisone would
have been reasonably expected by one of ordinary skill in the art at the time
of the invention. Appellant did not provide evidence that the time-lag form
was responsible for the improved results, and if so, that such a result was not
simply an inherent property of using the known time-lag prednisone. “Mere
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recognition of latent properties in the prior art does not render nonobvious
an otherwise known invention.” In re Baxter Travenol Labs., 952 F.2d 388,
392 (Fed. Cir. 1991).
For the foregoing reasons, the rejections of claims 48 and 49 are
affirmed. Claims 50, 51, and 54—56 fall with claim 48 because separate
reasons for their patentability were not provided. 37 C.F.R. 41.37(c)(iv).
REJECTION 3
Claim 52 and 53, depend from claim 48, and recited dosages of 2 mg
and 1 mg, respectively. The Examiner found that Buckley teaches utilizing
lower doses of prednisone, such 1^4 mg/day, to avoid the decline in bone
mineral associated with higher dose prednisone. Final Act. 9.
Appellant contends “one of skill in the art, as guided by Buckley
would be hesitant to use glucocorticoids for long-term treatment of RA.”
Appeal Br. 12. This argument is not persuasive because the claims do not
require a specific duration of treatment. Appellant did not identify an error
in the Examiner’s determination of the advantages of lower dose of
prednisone.
TIME PERIOD
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)(iv).
AFFIRMED
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