Ex Parte Fiala

Patent Trials and Appeals Board

May 16, 2019

12513215 - (D) (P.T.A.B. May. 16, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO.
12/513,215
131673 7590
Arent Fox LLP
800 Boylston Street
Prudential Tower
Boston, MA 02199
FILING DATE FIRST NAMED INVENTOR
06/11/2009 KaareFiala
05/20/2019
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.
19834-21 1346
EXAMINER
HAMA, JOANNE
ART UNIT PAPER NUMBER
1647
NOTIFICATION DATE DELIVERY MODE
05/20/2019 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):
Lin.Hymel@arentfox.com
Kimberly .W almsley@arentfox.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KAARE FIALA 1
Appeal2018-004926
Application 12/ 513,215
Technology Center 1600
Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
JOHN G. NEW, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellant identifies Savara Inc. as the real party-in-interest. App. Br. 3.
Appeal2018-004926
Application 12/ 513,215
SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 14, 15, and 28-33 as unpatentable
under 35 U.S.C. § 103(a) as obvious over R. Tazawa et al., Granulocyte-
macrophage colony-stimulating factor inhalation therapy for patients with
idiopathic pulmonary alveolar proteinosis: a pilot study; and long-term
treatment with aerosolized granulocyte-macrophage colony-stimulating
factor: a case report, 11 RESPIROLOGY S61-S64 (2006) ("Tazawa"); B.
Wang et al., Diagnosing Pulmonary Alveolar Proteinosis, 111 CHEST 460-
66 ( 1997) ("Wang"), J. Armitage, Emerging Applications of Recombinant
Human Granulocyte-Macrophage Colony-Stimulating Factor, 92 BLOOD
4491-508 (1998) ("Armitage"), P. Anderson et al., Aerosol Granulocyte
Macrophage-Colony Stimulating Factor: A Low Toxicity Lung-specific
Biological Therapy in Patients with Lung Metastases, 5 CLIN. CANCER RES.
2316-323 (1999) ("Anderson"), and Grabstein et al., (WO 88/00832,
February 11, 1988) ("Grabstein").
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellant's invention is directed to methods for enhancing pulmonary
host defense in a subject by administering, via inhalation, an effective
amount of granulocyte-macrophage colony stimulatory factor or a functional
homologue thereof See Abstract
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Application 12/ 513,215
REPRESENTATIVE CLAIM
Claim 14 is representative of the claims on appeal, and recites:
14. A method for treating pulmonary diseases selected from
the group consisting of pneumonia with bacterial and/or fungal
and/or viral infection or colonization or Pneumocystis carinii
pneumonia; cystic fibrosis with bacterial and/or fungal and/or
vira1 infection or colonization; bronchitis with bacterial and/or
fungal and/or viral infection or colonization; bronchiectasis with
bacterial and/or fungal and/or viral infection or colonization; and
bronchiolitis with bacterial and/or fungal and/or viral infection
or colonization of the pulmonary system in a human subject,
compnsmg pulmonary administration of granulocyte-
macrophage colony-stimulating factor (Gl\1-CSF) or a functional
homologue thereof comprising at least 80 consecutive amino
acids of SEQ ID NO: 1 and having at kast 95%i sequence identity
with mature human Gl'v1-CSF~ wherein a nebulized solution or a
suspension of GI'v1-CSF or said functional homologue thereof is
administered to said subject in an amount effective to reduce said
infection or colonization.
App. Br. 18.
ISSUES AND ANALYSES
We are persuaded by, and adopt, the Examiner's findings, reasoning
and conclusion that Appellant's claims are prima facie obvious over the
combined prior art. We address the arguments raised by Appellant below.
Issue 1
Appellant argues that the Examiner erred in concluding that the claims
are obvious over the combined cited prior art because the references would
not have led a person of ordinary skill in the art to a reasonable expectation
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of success in treating pulmonary infections by pulmonary administration of
GM-CSP. App. Br. 8.
Analysis
The Examiner finds that Tazawa teaches methods of alleviating the
symptoms of pulmonary disease by administering GM-CSP to the lungs of
human patients. Non-Final Act. 8, mailed January 12, 2016 (citing Tazawa
S62). The Examiner finds that, although Tazawa does not expressly teach
treatment of infection-based etiologies, Wang teaches that pulmonary
alveolar proteinosis (PAP), as taught by Tazawa, has multiple etiologies
including those that are infection-based, and Armitage teaches treatment of a
variety of bacterial, fungal and viral infections using GM-CSP in systemic
administration dosage form. Id. (citing Wang, 460-461 and Armitage 5-8).
The Examiner also finds that Anderson teaches methods of treating
pulmonary diseases by administering GM-CSP to the lungs of human
patients. Non-Final Act. 8 (citing Anderson 2316). The Examiner finds that
Anderson provides a mechanism for how inhaled GM-CSP acts in the lungs
to fight infections, since it teaches that GM-CSP is known to promote
increased numbers and cytotoxicity of activated macrophages, CD4+ T-
cells, cell accessory function, natural killer cell activity, and facilitation of
immune responsiveness via dendritic cells. Final Act. 6 ( citing Anderson
2321 ).
The Examiner finds that Grab stein teaches treatment of bacterial
disease, including pneumococcal infections (i.e., pneumonia) with GM-CSP.
Non-Final Act. 9 (citing Grabstein 1-2). The Examiner finds that Grabstein
teaches that GM-CSP may be administered in any convenient manner
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including dosage forms comprising inhalable aerosols. Id. ( citing Grab stein
2, 7).
The Examiner concludes that it would have been obvious to a person
of ordinary skill in the art to treat pulmonary disorders involving bacterial,
fungal, or viral infections in subjects susceptible to infections, including
subjects with cystic fibrosis, based on the teachings of the cited references.
Non-Final Act. 9. The Examiner concludes that given the mechanism of
action of how GM-CSP works when administered to the lungs, the treatment
of infections in pneumonia caused by pneumococcal infections, as well as a
variety of other pulmonary disorders and concomitant infections would be
predictable. Id.
Appellant argues that some of the references (Armitage, Grabstein)
teach general treatment of infection with GM-CSP, but not pulmonary
administration, while others (Tazawa, Anderson) teach the pulmonary
administration of GM-CSP, but not for treating infection. App. Br. 7.
Appellant asserts that none of the cited references individually discloses
every feature of Applicant's claims. Id.
Specifically, Appellant argues that Tazawa describes a GM-CSP
replacement therapy but does not suggest that GM-CSP could be effective in
treating infections. App. Br. 11. According to Appellant, Grabstein is
speculative and not credible. Id. at 10. Appellant contends that Armitage
teaches the use of GM-CSP to treat infections, but only by intravenous or
subcutaneous injection. Id. at 8. Appellant argues that Anderson teaches
only treatment of lung metastases and excluded patients with uncontrolled
lung infections, and that an immune response suitable for treating lung
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metastases is not predictive of an immune response for treating lung
infections as GM-CSP is toxic at high doses. Id.
Appellant next points to the Declaration of Dr. Bruce Trapnell, filed
December 19, 2016 (the "Trapnell Declaration"). App. Br. 7. Appellant
contends that Dr. Trapnell provides evidence of unpredictability and lack of
reasonable expectation of success. Id. (citing Trapnell Deel. 4--5).
Appellant argues that the Trapnell Declaration demonstrates that the route of
administration of GM-CSP is not generalizable, citing S. Herold et al.,
Inhaled Granulocyte/Macrophage Colony-Stimulating Factor as Treatment
of Pneumonia-associated Acute Respiratory Distress Syndrome, 189
AMERICAN J. OF RESP. CRIT. CARE MED. 609---611 (2014) ("Herold") and K.
Steinwede et al., Local delivery of Granulocyte/Macrophage Colony
Stimulating Factor protects mice from lethal pneumococcal pneumonia, 187
J. IMMUNOL. 5346-5356 (2011) ("Steinwede") as post-filing evidence that
systemic administration of GM-CSP was not effective in treating lung
infections. Id. at 9-10. Appellant also contends that the Trapnell
Declaration demonstrates that the generalized teachings of Grabstein
regarding routes of administration of GM-CSP are speculative and not
credible. Id. at 10. Therefore, Appellant asserts, there was significant
unpredictability regarding the route of administration and the type of
condition being treated such that there would not have been a reasonable
expectation of success to arrive at the claimed invention. Id. at 12-13.
We are not persuaded by Appellant's arguments. Appellant argues
that "[ n Jone of the references individually discloses every feature of
Applicant's claims" and identifies claim limitations missing from each
reference. App. Br. 7. However, "[O]ne cannot show non-obviousness by
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attacking references individually where ... the rejections are based on
combinations of references." In re Keller, 642 F.2d 413, 426 (C.C.P.A.
1981 ).
Appellant's arguments seek to establish that there was "considerable
uncertainty whether pulmonary administration of GM-CSP would result in
treatment" of pulmonary infection. App. Br. 8. However, certainty of
success is not the requisite standard. "Obviousness does not require absolute
predictability of success .... For obviousness under§ 103, all that is required
is a reasonable expectation of success." In re O 'Farrell, 853 F.2d 894, 903-
04 (Fed. Cir. 1988).
Appellant relies upon the Trapnell Declaration as providing evidence
of the uncertainty or unpredictability of using GM-CSP for treating
pulmonary infection. App. Br. 9-10. The Declaration states that
pharmacokinetics and drug administration are unpredictable, and it cannot
be assumed that a drug administered effectively by one route of
administration can be administered effectively by a different route of
administration. Trapnell Deel. 3. As proof of this assertion, the declaration
cites two post-filing references, Herold and Steinwede, for teaching that
systemic administration of GM-CSP was not effective in patients with sepsis
induce lung injury, or when given as a prophylactic, protective treatment
against pneumococcal pneumonia. However, Appellant's claims on appeal
are not directed to systemic administration of GM-CSP for treating
pulmonary infections, but rather are directed to pulmonary administration of
GM-CSP. Therefore, the key issue is the level of predictability for
pulmonary administration of GM-CSP to treat pulmonary infection. To the
extent that the evidence addresses pulmonary administration, Herold and
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Steinwede confirm the effectiveness of pulmonary administration of GM-
CSP for treating pulmonary infection suggested by Grabstein (Grabstein 2,
7).
Appellant also contends that Grabstein teaches only the treatment of
typhus in a mouse model by intraperitoneal injection of GM-CSP and then
speculates, without any evidence, that all routes of administration of GM-
CSP can be used to treat any infection. App. Br. 10. Appellant argues that
the Trapnell Declaration provides evidence that Grabstein's teachings are
not credible. Id.
We do not agree. A reference may be relied upon for all that it would
have reasonably suggested to one having ordinary skill in the art. Merck &
Co. v. Biocraft Labs., 874 F.2d 804, 807 (Fed. Cir. 1989). We treat
Appellant's arguments relating to the lack of credibility of Grabstein as
addressing whether the reference provides a reasonable expectation of
success in practicing the methods of treating infection, in view of the
asserted evidence of unpredictability cited in the Trapnell Declaration. 2 As
discussed supra, the Trapnell declaration cites two specific situations where
systemic GM-CSP was not effective as evidence of the asserted
unpredictability regarding GM-CSP administration. The first reference,
Herold, teaches treating sepsis-induced lung injury by administration of
2 Appellant also argues in their Reply Brief that Grabstein's claims are non-
enabled. However, we need not reach arguments made in the Reply Brief
that could have been included in the Appeal Brief, but were not. See Ex
parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (Informative):
Arguments not raised in the Appellate Brief are considered waived. ("[T]he
reply brief [is not] an opportunity to make arguments that could have been
made in the principal brief on appeal to rebut the Examiner's rejections, but
were not").
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systemic GM-CSP, which is not a condition taught by Grabstein. Herold
609; Trapnell Deel. 4. The Trapnell Declaration states that Steinwede
teaches that prophylactic administration of GM-CSP systemically had no
protective effects against pneumococcal pneumonia. Steinwede 11-12;
Trapnell Deel. 5. However, Steinwede has little relevance to the teachings
of Grabstein, which teaches methods for treating subjects "suffering from an
infectious disease," and not for prophylactic treatment methods, as cited by
the Trapnell Declaration. See Grabstein 2; Trapnell Deel. 5. Moreover, a
single experimental study in which GM-CSP administration was not
effective does not necessarily mean that it would be ineffective against
infection in general, or that the teachings of Grabstein are not credible.
Grabstein teaches that GM-CSP can be administered to subjects "by a
variety of conventional parenteral routes," and specifically teaches "dosage
forms, such as injectable solutions, inhalable aerosols, suppositories, and
the like." Grabstein 6-7 (emphasis added). Grabstein teaches that GM-CSP
functions to "promote host immune response," that GM-CSP "may cause
macrophages and/or granulocytes to function more efficiently, especially in
killing bacteria," and that GM-CSP can "facilitate the removal of dead
bacterial cells." Id. at 6. Appellant has not provided persuasive evidence to
counter the teachings of Grab stein regarding the use of parenteral GM-CSP
for treatment of infection by promoting host immune responses against
bacterial infection.
Appellant also argues that Anderson teaches that GM-CSP is toxic at
high doses, and that Anderson's limited treatment effects obtained with
tumors are not generalizable to treatment of lung infections. App. Br. 12.
However, Anderson's teachings regarding the toxicity of GM-CSP relate to
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intravenous doses, stating that "i.v. high-dose GM-CSP infusions> 1 week
have been associated with side effects." Anderson, 2320. Anderson also
emphasizes that aerosolized GM-CSP was non-toxic, stating that the
"absence of toxicity of aerosolized yeast-derived recombinant human GM-
CSP is one of the more important observations of this study." Id. Anderson
further teaches the effectiveness and desirability of aerosol delivery of GM-
CSP stating that it "provides a means to achieve local effects in the lung
with minimal systemic drug exposure" and that it "appears to be feasible and
without symptoms in most patients." Id. at 2321. Anderson also teaches
that GM-CSP, when administered to the lung, has multiple effects on
immune function and promotes "increased numbers and cytotoxicity of
activated macrophages, CD4 T-cells, improved cell accessory function,
increased natural killer cell activity, and facilitation of immune
responsiveness via dendritic cells." Id. Appellant has not advanced
sufficient evidence or reasoning as to why the teachings of Anderson
regarding immune stimulating effects to GM-CSP in the lung would not be
applicable to infection, particularly in light of the teachings of Grabstein
described supra.
Consequently, we agree with the Examiner's findings and conclude
that the combination of references would provide a reasonable expectation
of success to arrive at Appellant's claimed method.
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Issue 2
Appellant argues that the Examiner erred in concluding that the claims
are obvious over the combined cited prior art, because the claimed method
provides a solution to a long-felt and unmet need. App. Br. 15.
Analysis
Appellant contends that the present invention provides a solution to a
long-felt need for treating pulmonary infection, and that since aerosolized
GM-CSP was available for 10 years prior to filing date of the present
invention, the lack of an anticipatory reference to the presently claimed
method demonstrates that the problem was not solved by others. App. Br.
15.
We are not persuaded. Establishing long-felt need requires objective
evidence and Appellant relies solely on attorney argument, not evidence.
Furthermore, to establish long-felt need, Appellant must show: (1) a need
has been a persistent one that was recognized by ordinarily skilled artisans;
(2) the long-felt need must not have been satisfied by another before
Appellant's invention; and (3) the invention must, in fact, satisfy the long-
felt need. In re Gershon, 372 F.2d 535, 538 (CCP A 1967); Newell Co. v.
Kenney Mfg. Cos., 864 F.2d 757, 768 (Fed. Cir. 1988); In re Cavanagh, 436
F.2d 491,496 (CCPA 1971).
Appellant identifies the long-felt need as a treatment for pulmonary
infection, but the evidence of record supports the conclusion that this
problem has been satisfied by prior art treatments. For example, as pointed
out by the Examiner, Armitage teaches the treatment of pulmonary diseases
associated with infection of the pulmonary system by a variety of bacterial,
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fungal, and viral pathogens using GM-CSP systemically. Ans. 19.
Furthermore, the background section of Grab stein also teaches that
infectious bacterial diseases are typically treated with antibiotics or
sulfonamides, a treatment which has resulted in the saving of countless lives.
Grabstein 2. Moreover, the fact that an anticipatory reference was not cited
by the Examiner is not sufficient evidence to demonstrate all of elements
(1 }-(3) above.
We consequently conclude that the Examiner has established a prima
facie case of obviousness over the combined cited prior art, and we affirm
the Examiner's rejection of the claims.
DECISION
The Examiner's rejection of claims 14, 15, and 28-33 under 35 U.S.C.
§ 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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