Ex Parte Klaus et al

Patent Trial and Appeal Board

Oct 13, 2016

13180262 (P.T.A.B. Oct. 13, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO.
13/180,262
41385 7590
FIBROGEN, INC.
409 Illinois Street
FILING DATE
07 /11/2011
10/13/2016
San Francisco, CA 94158
FIRST NAMED INVENTOR
Stephen J. Klaus
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.
FP0628. l CON 2125
EXAMINER
CHONG,YONGSOO
ART UNIT PAPER NUMBER
1627
MAILDATE DELIVERY MODE
10/13/2016 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte STEPHEN J. KLAUS, INGRID LANGSETMO PAROBOK, and
CHRISTOPHER T. JACOB
Appeal2015-000745 1
Application 13/180,262
Technology Center 1600
Before DONALD E. ADAMS, JOHN G. NEW, and RYAN H. FLAX,
Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a method for treating stroke patients. Claims 15-26 are
on appeal as rejected under 35 U.S.C. §§ 102(b) and 103(a). We have
jurisdiction under 35 U.S.C. § 6(b). We reverse as to claim 20 and affirm as
to all other claims.
1 The Real Party in Interest is FibroGen, Inc. Br. 3.
Appeal2015-000745
Application 13/180,262
STATEMENT OF THE CASE
The appealed claims can be found in the Claims Appendix of the
Appeal Brief. Claim 15 is the sole independent claim, is representative, and
reads as follows:
15. A method for treating a subject suspected of having had a
stroke, prior to diagnosis of the stroke as an ischemic stroke or a
hemorrhagic stroke, the method comprising the steps of:
a) administering a first dose of a compound which inhibits
hypoxia inducible factor (HIP) prolyl hydroxylase activity to the
subject; and
b) subsequently diagnosing the stroke as an ischemic stroke or a
hemorrhagic stroke.
Br. 18 (Claims App'x). Claims 18-23 are separately rejected and argued,
and read as follows:
18. The method of claim 15, wherein the step of administering
the first dose occurs at least 3 hours after onset of the stroke.
19. The method of claim 15, wherein the subject is subsequently
diagnosed as having had an ischemic stroke and the method
further comprises the additional step of: administering a
thrombolytic agent to the subject.
20. The method of claim 19, wherein the administering of the
thrombolytic agent occurs at least 3 hours after onset of the
stroke.
21. The method of claim 19, wherein the thrombolytic agent is
tissue plasminogen activator (tPA).
22. The method of claim 15, wherein the subject is subsequently
diagnosed as having had an ischemic stroke and the method
further comprises the additional step of: administering a second
dose of the compound at or subsequent to reperfusion.
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23. The method of claim 15, wherein the administering of the
second dose of the compound occurs at least 24 hours after
administering the first dose.
Id. 18-19.
The following rejections are on appeal:
Claims 15-17 and 24- 26 stand rejected under 35 U.S.C. § 102(b)
over Guenzler. 2 Final Action 5.
Claims 18-23 stand rejected under 35 U.S.C. § 103(a) over Guenzler
and Grotta.3 Final Action 7.
Claims 15-17 and 25-26 stand rejected under 35 U.S.C. § 103(a) over
Guenzler and Arend.4,5 Final Action 10.
Except where otherwise indicated, we adopt the Examiner's findings
of fact, reasoning on scope and content of the prior art, and conclusions set
out in the Final Action and Answer. Any findings of fact set forth below are
provided to highlight certain determinations by the Examiner or identify
facts established by Appellants.
FINDINGS OF FACT
FF 1. Guenzler disclosed:
In a preferred embodiment, the present invention provides a
method of treating, preventing, or pretreating a HIP-associated
2 U.S. Patent Application Pub. No. US 2003/0176317 Al (published Sept.
18, 2003) (hereinafter "Guenzler").
3 U.S. Patent Application Pub. No. US 2002/0137758 Al (published Sept.
26, 2002) (hereinafter "Grotta").
4 U.S. Patent No. US 7,928,120 B2 (issued to Arend et al. on Apr. 19, 2011)
(hereinafter "Arend").
5 This rejection is found to be cumulative of the rejection under 35 U.S.C.
§ 102 and, therefore, we vacate this rejection.
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Application 13/180,262
condition in a subject, the method comprising inhibiting HIP
prolyl hydroxylase enzyme activity. Again, HIP-associated
conditions include those associated with hypoxia, or with
ischemia, etc. In a particular embodiment, the method comprises
administering to the subject a compound that inhibits HIP prolyl
hydroxylase activity.
Guenzler ii 22; see also Final Action 5-6 (discussing Guenzler).
FF2. Guenzler also disclosed, "[i]n particular embodiments,
the compound is a heterocyclic carboxamide." Guenzler ii 19; see also
Final Action 5-6 (discussing Guenzler).
FF3. Guenzler taught various embodiments compnsmg
treating ischemia-related disorders, e.g., "indicative of a stroke," both
after and before a diagnosis thereof, in that Guenzler disclosed:
Methods of preconditioning or pretreating are specifically
contemplated. In one embodiment, the invention provides
methods of pretreating or preconditioning wherein HIFa is
stabilized prior to the occurrence of an event associated with a
HIP-associated condition, e.g., ischemia, etc., or the
development of a HIP-associated condition. Ischemias can be
induced by acute events. Such events can include, for example,
surgery, e.g., angioplasty, organ transplantation, etc., and related
procedures such as administration of anesthesia, etc.
Furthermore, chronic events specific embodiments, the methods
of pretreating or preconditioning are applied in situations where
a subject has a disorder predictive of the development of a HIF-
associated condition, e.g., transient ischemic attack or angina
pectoris, indicative of stroke and myocardial infarction,
respectively, in order to prevent the development of or reduce the
degree of development of the HIP-associated condition.
Guenzler ii 25; see also Final Action 5-6 (discussing Guenzler).
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FF4. Guenzler taught vanous embodiments compnsmg
treating ischemia-related disorders, e.g., "indicative of a stroke," both
after and before a diagnosis thereof, in that Guenzler disclosed:
In one specific embodiment, the compound is administered
immediately following the diagnosis of an acute ischemic
disorder. In another specific embodiment, the compound is
administered to a subject during the course of a chronic ischemic
condition. In yet another specific embodiment, the ischemia is
due to a transient or acute trauma, insult, or injury such as, e.g.,
a spinal cord injury.
Guenzler iJ 30; see also Final Action 5-6 (discussing Guenzler).
FF5. Guenzler taught various embodiments comprising
treating ischemia-related disorders, e.g., "indicative of a stroke," both
after and before a diagnosis thereof, in that Guenzler disclosed:
In one embodiment, the compound is administered immediately
following a condition producing acute ischemia, e.g., myocardial
infarction, pulmonary embolism, intestinal infarction, ischemic
stroke, and renal ischemic-reperfusion injury. In another
embodiment, the compound is administered to a patient
diagnosed with a condition associated with the development of
chronic ischemia, e.g., cardiac cirrhosis, macular degeneration,
pulmonary embolism, acute respiratory failure, neonatal
respiratory distress syndrome, and congestive heart failure. In
yet another embodiment, the compound is administered
immediately after a trauma or injury.
GuenzleriJ 203; see also Final Action 5-6 (discussing Guenzler).
FF6. Guenzler disclosed, "[ d]osage amount and interval
may be adjusted individually to provide plasma levels of the active
moiety that are sufficient to modulate HIP a stabilization and HIP -
regulated gene induction, as desired," and "[t]he amount of agent or
composition administered will, of course, be dependent on a variety of
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factors, including the sex, age, and weight of the subject being treated,
the severity of the affliction, the manner of administration, and the
judgment of the prescribing physician." Guenzler iii! 230 and 231; see
also Final Action 5-6 (discussing Guenzler).
FF7. Grotta disclosed, "[ w ]hile intravenous thrombolytic
treatments have shown promise, they generally require intervention
within three hours of a stroke. Other unproven oral drug treatments
may be initiated within a 24-hour post-stroke window and may
positively affect neurological outcome with continued dosage for three
months after a stroke." Grotta iJ 5; cf Br. 14-15 (contending it was
understood that stroke therapy should be administered within 3 hours
of stroke).
FF8. Grotta disclosed, "[t]he present inventors have
recognized the need for an effective and safe treatment for human
stroke and other head related trauma. Except for the tissue plasminogen
activator [tPA] that is used in the clinic to recanalyze occluded vessels,
there is no other effective treatment for management of stroke and
related diseases." Grotta iJ 8; see also Final Action 7-8 (discussing
Grotta).
FF9. W ang6 disclosed, "tP A therapy may work best if
administered within a narrow 1- to 3-hour therapeutic window after
stroke onset. Although some intriguing evidence exists to suggest that
6 Xiaoying Wang, PhD, et al., Mechanisms of Hemorrhagic Transformation
After Tissue Plasminogen Activator Reperfusion Therapy for Ischemic
Stroke, 35 STROKE, J. AM. HEART Assoc. 2726-30 (2004) (hereinafter
"Wang").
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some patients may also benefit from later tP A treatments, the criteria
for identifying these patient subsets need to be precisely defined."
Wang 2726 (left col.); see also Br. 14 (contending Wang is evidence
that it was understood that therapeutic agents could only be
administered within 3 hours of stroke).
FFlO. Wang also disclosed, "the clinical problem at hand is
how to increase the time window for tP A, decrease or eliminate the
risks of cerebral hemorrhage, and ultimately to increase the overall
efficacy of tPA reperfusion therapy." Wang 2716 (left col.); see also
Br. 14 (contending Wang is evidence that it was understood that
therapeutic agents could only be administered within 3 hours of stroke).
FF 11. Genentech 7 disclosed:
1 INDICATIONS AND USAGE
1.1 Acute Ischemic Stroke
Activase is indicated for the treatment of acute ischemic stroke.
Exclude intracranial hemorrhage as the primary cause of stroke
signs and symptoms prior to initiation of treatment [see
Contraindications (4.1)]. Initiate treatment as soon as possible
but within 3 hours after symptom onset.
Genentech 2; see also Br. 15 (contending Genetech is evidence that it was
understood that tP A must be administered within 3 hours of stroke).
7 Genentech, Inc., Prescribing Information for ACTIVASE, Package Insert
(available at http://www.gene.com/ download/pdf/ activase _prescribing. pdf,
visited Oct. 4, 2016) (hereinafter "Genentech").
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DISCUSSION
The rejection under 35 U.S. C. § 102(b) over Guenzler.
The Examiner has established a prima facie case that claims 15-17
and 24- 26 are anticipated by Guenzler. See, e.g., FF l-FF6. We address
Appellants' arguments below.
Appellants argue that the language of claim 15 should be interpreted
so that the preamble is a limitation. Br. 9. Appellants contend that if the
preamble language, "treating a subject suspected of having a stroke, prior to
diagnosis of the stroke as an ischemic stroke or a hemorrhagic stroke," is a
limitation, it is not disclosed by Guenzler and, so, the claim is not
anticipated. Id. 9-10. Appellants' argument is not persuasive.
Even assuming, for the sake of argument, that the preamble were a
limitation, its elements are disclosed by Guenzler. Guenzler discloses
administering its HIP inhibition therapy "where a subject has a disorder [or
injury] predictive of the development of a HIP-associated condition, e.g.,
transient ischemic attack or angina pectoris, indicative of stroke." FF3
(emphasis added); see also FF4 and FF5. This is a disclosure of treating a
subject suspected of, but not yet diagnosed as having had a stroke, as recited
in the preamble. Other embodiments disclosed by Guenzler relate
alternatively to first diagnosing the condition and then treating.
Appellants also argue that the claims provide methods where, i.e.,
requiring that, the treatment can be administered to a subject who has had a
hemorrhagic stroke and that, because Guenzler does not disclose such a
treatment, the claims are not anticipated. This argument is not persuasive.
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The claim language may be inclusive of treatments for patients of
hemorrhagic stroke, but the claims recite "diagnosing the stroke as an
ischemic stroke or a hemorrhagic stroke." See claim 15, supra. This claim
language is posed in the alternative and cannot reasonably be read to require
the occurrence, treatment, or diagnosis of hemorrhagic stroke. Therefore, if
either ischemic or hemorrhagic stroke occurs, is treated, and is diagnosed,
the claim is satisfied.
For the above reasons, we find that the preponderance of evidence
supports the Examiner's determination that the claims are anticipated by
Guenzler. We affirm the rejection.
The rejection under 35 U.S.C. § 103(a) over Guenzler and Grotta.
The Examiner has established a prima facie case that claims 18, 19,
and 21-23 would have been obvious over Guenzler and Grotta. See, e.g.,
FF l-FF6 and FF8. The disclosure of Grotta cited by the Examiner suggests
that tP A is an effective treatment for management of stroke and related
diseases, which is reason to combine it with the treatments disclosed by
Guenzler as also for treating stroke, as discussed above. FF8.
We are, however, persuaded by Appellants' arguments that claim 20
would not have been obvious over the prior art combination. We address
Appellants' arguments below.
Appellants argue that the Examiner's determination that the timing of
therapy administration was an optimizable, results effective variable was
unsupported by the facts. We find the evidence does not support this
contention.
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The Examiner determined that "it is well-known in the art for dosage
amounts and intervals of the active agents to be adjusted individually based
on a variety of factors, including the sex, age, weight, severity of the
affliction, manner of administration, and judgment of the prescribing
physician," which is supported by the disclosure of Guenzler. Final Action
7-8; FF6. Guenzler also indicated that"[ d]osage amount and interval may
be adjusted individually to provide plasma levels of the active moiety that
are sufficient to modulate HIFa stabilization and HIP-regulated gene
induction, as desired," which is evidence that the timing and/ or frequency of
therapy administration is a results effective variable with potential for
optimization. See FF6.
Appellants also argue that, according to Grotta, tP A would only be
administered after diagnosis of a stroke as an ischemic stroke. Br. 14. We
are not persuaded. Grotta suggests that tP A is an effective treatment for
management of stroke and related diseases, which is the very subject matter
of Guenzler. Therefore, it would have been obvious to combine the two
disclosures and add the Grotta-disclosed tPA administration to the Guenzler
HIP-inhibitor administration, which is disclosed in Guenzler as occurring
prior to diagnosis. FF3-FF6. "It is primafacie obvious to combine two
compositions each of which is taught by the prior art to be useful for the
same purpose, in order to form a third composition which is to be used for
the very same purpose. . . . [T]he idea of combining them flows logically
from their having been individually taught in the prior art." In re
Kerkhoven, 626 F.2d 846, 850 (CCPA 1980). Moreover, there is no claim
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limitation that the tP A or thrombolytic agent must be administered before a
diagnosis. Therefore, Appellants' argument is not persuasive.
Appellants also argue that, as applied to the field of stroke therapy, it
was understood that therapeutic agents could only be safely administered
within 3 hours of stroke onset and, for this reason, the claims directed to
extending the time window for tP A administration were not directed to
merely optimizing such ranges and were nonobvious for this reason. Br. 14-
15. We agree, to a degree, with Appellants' contention.
"' [I]it is not inventive to discover the optimum or workable ranges by
routine experimentation.' In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Only if the 'results of optimizing a variable' are 'unexpectedly good' can a
patent be obtained for the claimed critical range. In re Antonie, 559 F.2d
618, 620 (CCPA 1977)." In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir.
1997) (internal cites to USPQ omitted). "In general, an applicant may
overcome a prima facie case of obviousness by establishing 'that the
[claimed] range is critical, generally by showing that the claimed range
achieves unexpected results relative to the prior art range."' In re Peterson,
315 F.3d 1325, 1330 (Fed. Cir. 2003).
Appellants identify evidence in support of their contention regarding
the recited therapy timing, but only as to thrombolytic agents. See Br. 14-
15. Specifically, Appellants cite Wang and Genentech. Id. Wang suggests
that tP A works best when administered within a 3 hour window after stroke
(but also suggests that there may be evidence that patients might benefit
from later tP A treatments, without further explanation) and suggests a desire
in the field to increase this time window, further suggesting that the problem
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had not been solved. FF9-FF10. Genentech is directed to an FDA-
approved tP A drug, i.e., Activase, and indicates that treatment therewith
must occur within 3 hours after symptoms (of stroke). FF 11. Moreover, it
is not cited as support by Appellants, but Grotta suggests that thrombolytic
treatments, such as tPA, are generally required to be administered within 3
hours of a stroke (while other, unproven treatments may be initiated later).
FF7.
We are persuaded by this evidence that, as to thrombolytic treatments,
specifically tP A, it was understood in the art that there was a 3-hour, post-
stroke window for treatment. This evidence, however, does not extend, as
Appellants suggest, to any and all stroke therapies. See, e.g., FF7.
Therefore, as to claims 18, 19, and 21-23, which are respectively
directed to administering HIP inhibitor 3 hours or later after stroke, adding
thrombolytic agent administration to the method of claim 15, adding tP A
administration to the method of claim 15, adding another HIP inhibitor
administration to the method of claim 15, and adding a second
administration of HIP inhibitor at least 24 hours after the first, we find the
preponderance of evidence supports the Examiner's determination of
obviousness. As to claim 20, however, which is directed to extending the
administration window of a thrombolytic agent beyond 3 hours after a
stroke, we find that the preponderance of evidence supports the Appellants'
argument that the claim is nonobvious. We, therefore, affirm as to claims
18, 19, and 21-23 and reverse as to claim 20.
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SUMMARY
The rejection of claims 15-17 and 24-26 under 35 U.S.C. § 102(b)
over Guenzler is affirmed. The claims were argued together and fall with
claim 15. All claims fall with claim 15. 37 C.F.R. § 41.37(c)(l)(iv).
The rejection of claims 18-23 under 35 U.S.C. § 103(a) over Guenzler
and Grotta is affirmed as to claims 18, 19, and 21-23 and reversed as to
claim 20.
The rejection of claims 15-17 and 25-26 under 35 U.S.C. § 103(a)
over Guenzler and Arend is vacated as cumulative of the rejection under
§ 102(b).
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § l.136(a).
AFFIRMED-IN-PART
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