Ex Parte Fischer et al

Patent Trial and Appeal Board

Aug 21, 2018

14201119 (P.T.A.B. Aug. 21, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/201,119 03/07/2014
34725 7590 08/21/2018
CHALKER FLORES, LLP
14951 North Dallas Parkway, Suite 400
DALLAS, TX 75254
FIRST NAMED INVENTOR
Bernhard Fischer
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.
SONN:1026CON 4563
EXAMINER
MIKNIS, ZACHARY J
ART UNIT PAPER NUMBER
1675
MAIL DATE DELIVERY MODE
08/21/2018 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 BERNHARD FISCHER and RUDOLF LUCAS
Appeal2017-007135
Application 14/201, 119
Technology Center 1600
Before RICHARD M. LEBOVITZ, JEFFREY N. FRED MAN, and
MICHAEL J. FITZPATRICK, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134 involving claims to a
method for the prevention of edema in a patient suffering acute respiratory
distress syndrome by treating with cyclized peptide. The Examiner rejected
the claims as anticipated. We have jurisdiction under 35 U.S.C. § 6(b ). We
affirm.
1 Appellants identify the Real Parties in Interest as Apeptico Forschung und
Entwicklung GMBH (see App. Br. 2).
2 We have considered and herein refer to the Specification of June 16, 2014
("Spec."); Final Office Action of May 9, 2016 ("Final Action"); Appeal
Brief of Nov. 4, 2016 ("App. Br."); Examiner's Answer of Feb. 7, 2017
("Answer"); and Reply Brief of Apr. 6, 2017 ("Reply Br.").
Appeal2017-007135
Application 14/201, 119
Statement of the Case
Background
"Epithelial cells form single- or multi-layer cell layers, which cover
all inner and outer body surfaces of the human and animal organs" (Spec.
,r 4). "An injury of the endothelium and the epithelium may cause a so-
called hyperpermeability, i.e. an uncontrolled passage of liquid from blood
vessels into vital organs and tissues" "and thus seriously damage the
functionality of the organs" (id. ,r 6-7). "Hyperpermeability of lung tissues
is an essential component of various diseases of the lungs, e.g. acute lung
injury, acute respiratory distress syndrome (ARDS), pneumonia" (id. ,r 15).
The Claims
Claims 1, 6, and 13 are on appeal. Claim 1 is representative and reads
as follows:
1. A method for the prevention of edema in a patient
suffering acute respiratory distress syndrome (ARDS) by
prevention of hyper-permeability, based on injuries of the
endothelium and epithelium layers, comprising the steps of:
identifying the patient with (ARDS) prior to the onset of
edema; and
providing the patient with an amount of a peptide
consisting of the amino acid sequence
CGQRETPEGAEAKPWYC (SEQ ID NO: 1) and that is
cyclized via the C residues sufficient to prevent the entry of
fluid via the endothelium of the capillaries into the epithelium
of the lung at the alveoli to reduce an amount of fluid that
enters a lung of the patient before edema occurs within the lung
of the patient, by increasing the expression of epithelial sodium
channel and inhibiting the activation of Protein Kinase C in the
endothelium of the capillaries.
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The Rejection3
The Examiner has rejected claims 1, 6, and 13 under 35 U.S.C.
§ 102(b) as anticipated by Lucas4 (Final Act. 3---6).
The Examiner finds Lucas teaches "the circularized peptide
CGQRETPEGAEAKPWYC" "containing a disulfide between cysteines"
"for the treatment of edema ... including ARDS" (Final Act. 4). The
Examiner finds Lucas teaches
(Id.).
patients with ARDS have dramatically decreased edema
resorption capacity (see e.g. Col. 21 lines 52-55). Further, the
model of lung reperfusion injury results in edema, and is a
model of ARDS (see e.g. Example 4). Thus, the patients being
treated in [Lucas] already have been identified as having ARDS
prior to the onset of edema.
The Examiner finds the functional recitations in claim 1 of inhibition
of activation of protein kinase C and increase in epithelial sodium channel
expression are inherent in the administration of the peptide (see id. at 5).
The Examiner finds overlapping dosage amounts between the Specification
and Lucas, and therefore finds administration of the same dosage "must
achieve the same result during treatment of edema in a patient suffering
from ARDS" (id. at 6).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner's conclusion that Lucas teaches
"prevention of edema" using the claimed peptide as required by claim 1?
3 The Examiner withdrew rejections under 35 U.S.C. § 112, first, second,
and fourth paragraphs and under 35 U.S.C. § 103(a) (see Ans. 5---6).
4 Lucas et al., US 7,258,861 B2, issued Aug. 21, 2007.
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Appeal2017-007135
Application 14/201, 119
Findings of Fact ("FF'')
1. Lucas teaches "the endothelium plays an essential role in
regulating the dynamic interaction between pulmonary vasodilatation and
vasoconstriction and is a major target during ischemia/reperfusion and acute
respiratory distress syndrome (ARDS)-related lung injury ... there is an
urgent need to efficiently prevent or treat pulmonary edema" (Lucas 1 :35-
43).
2. Lucas teaches "patients with ARDS or acute lung injury also
have a dramatically decreased edema resorption capacity, correlating with
morbidity and higher mortality" (Lucas 21:52-54).
3. Lucas teaches the "terms 'a pharmaceutical composition for
treating oedema' relates to any composition comprising a peptide as defined
above which prevents, ameliorates or cures oedema, in particular pulmonary
oedema" (Lucas 6:7-10).
4. Lucas teaches "the present invention aims at providing non-
toxic peptides derived from TNF which can be used to prevent or treat
oedema" (Lucas 2:66 to 3: 1)
5. Lucas, teaches, in Example 4, a "Rat Model of Lung
Reperfusion Injury (Warm Ischemia and Reperfusion): a Model of Acute
Respiratory Distress Syndrome (ARDS)" in which
rats (200-250 g) undergo clamping of the left pulmonary artery,
pulmonary vein and main bronchus for 36 minutes of warm
ischemia. After reperfusion of the left lung, the right lung is
occluded to assess the function of the left lung for 90 minutes.
The peptide is given at 3 minutes after reperfusion by either
instillation or intravenous injection via the subclavian vein.
(Lucas 15:1-15).
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Application 14/201, 119
6. Lucas teaches, in Example 4, that the
cyclic hum Ltip peptide: CGQRETPEGAEAKPWYC (SEQ ID
NO 4; with a disulfide bond between Cys at position 1 and
position 17) treated animals ( and this over a broad dosage
range, extending from 500 µg/kg to 5 µg/kg, have significantly
much better p02 levels and lower pC02 levels ( data not
shown) and are less suffering from fluid overload.
(Lucas 16:19-25).
7. Lucas teaches the drug "is given at a dose between 1 µg/kg and
10 mg/kg" (Lucas 6:35-36).
8. The Specification teaches the "drug is administered such that
the peptide of the present invention is administered at a dose of between 1
µg/kg and 10 µg/kg, more preferably between 10 µg/kg and 5 mg/kg" (Spec.
,r 33).
Principles of Law
The Examiner bears the initial burden of establishing a prima facie
case of anticipation. In re King, 801 F.2d 1324, 1326-27 (Fed. Cir. 1986).
Anticipation under 35 U.S.C. § 102 requires that "'each and every element
as set forth in the claim is found, either expressly or inherently described, in
a single prior art reference."' In re Robertson, 169 F.3d 743, 745 (Fed. Cir.
1999).
Analysis
We adopt the Examiner's findings of fact and conclusions of law (see
Final Act. 3-6; FF 1-8) and agree that Lucas anticipates the claims. We
address Appellants' arguments below.
Appellants contend the "claims are directed to a method that prevents
the occurrence of edema within the lung of an ARDS patient before any
edema occurs" (App. Br. 9). Appellants contend Lucas "provides a false
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Application 14/201, 119
definition for the expression 'a pharmaceutical composition for treating
edema' because the meaning of the term 'treatment' does not correctly
encompass the meaning of the term 'prevention'" (id. 10). Appellants
contend "[b ]ecause the Applicant(s) has/have defined the terms in question
after Lucas made his definitions, the definitions of the Applicant( s) are the
most current operable version of the definitions" (id. 11 ). 5
We find this argument regarding the proper interpretation of the claim
and prior art unpersuasive because the issue here is whether Lucas teaches
"prevention of edema" as required by claim 1. Lucas expressly teaches that
its compositions for "treating oedema" encompass a treatment that
"prevents, ameliorates, or cures oedema, in particular pulmonary oedema"
(FF 3). There is no inconsistency with Appellants' own definition. Lucas is
simply explaining the terms in its patent.
There is no reasonable doubt that Lucas teaches to prevent edema.
Lucas states "there is an urgent need to efficiently prevent or treat
pulmonary edema" (FF 1; emphasis added). Lucas teaches that one form of
treatment of edema includes preventing such edema (FF 3). Indeed, Lucas
explains "the present invention aims at providing non-toxic peptides derived
from TNF which can be used to prevent or treat oedema" (FF 4; emphasis
added). Thus, even if we agree with Appellants that the broadest reasonable
interpretation of "treating" edema need not necessarily encompass
prevention, Lucas specifically teaches edema prevention (FF 1, 3, 4),
satisfying the requirement of claim 1 for "prevention of edema."
5 We note that Appellants do not identify any specific statement in the
Specification defining either the terms "treatment" or "prevention" (see App.
Br. 11).
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Appellants contend "the Current Action's characterization of TIP
peptides (TIP peptides are peptides that mimic the lectin-like domain of
TNF-a) in the cited documents as being inherent with respect to the method
claims of the present invention is improper" (App. Br. 11 ). Appellants
contend "that preventing the 'entry of fluid via the endothelium of the
capillaries into the epithelium of the lung at the alveoli' does not
'necessarily' flow from the cited document" (id. 12). Appellants contend:
This property of the TIP peptide was not used in the prior art
because in the prior art the TIP peptide was never used for
prevention of an edema that is not yet generated but was only
used after development of edema to remove fluid after the
development of the disease in an ARDS patient. Applicant( s)
respectfully submit( s) that the use of TIP for the prevention of
edema is not inherently a function of TIP in light of the Lucas
'861 Patent
(App. Br. 13).
We find this argument unpersuasive because Lucas recognizes "there
is an urgent need to prevent ... edema" (Lucas, 1 :42--43), expressly equates
"treating" edema, with, among things, preventing it in the first instance (id.
at 1 :42--43, 6:7-10), and administers the exact same peptide as claim 1 to
patients with the exact same disease conditions as claim 1 in overlapping
dosage amounts consistent with the Specification (FF 1-8). In Montgomery,
the drug ramipril was administered to patients in need of stroke prevention
and the Court found that "efficacy is inherent in carrying out the claim
steps." In re Montgomery, 677 F.3d 1375, 1381 (Fed. Cir. 2012). Similarly
here, where Lucas teaches administration of the cyclized
CGQRETPEGAEAKPWYC peptide identical to that in claim 1 to the same
patient population suffering acute respiratory distress syndrome (FF 2, 4--5)
in doses overlapping with those recited in claim 1 (FF 5, 7, 8) "to prevent or
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Application 14/201, 119
treat oedema" (FF 4 ), we agree with the Examiner that there is a persuasive
case that such peptide administration would necessarily yield the functional
results recited in claim 1 of "increasing the expression of epithelial sodium
channel" and "inhibiting the activation of Protein Kinase C" (see Ans. 14--
15).
The Examiner cited evidence, Xiong6 and Shabbir, 7 to support the
inherency position (see Ans. 15), but we need not rely upon these references
because Lucas alone reasonably shifts the burden to Appellants to
demonstrate that the recited peptide, at the suggested dosages, would not
necessarily result in "increasing the expression of epithelial sodium channel"
and "inhibiting the activation of Protein Kinase C" because "[ w ]hether the
rejection is based on 'inherency' under 35 U.S.C. § 102, on 'prima facie
obviousness' under 35 U.S.C. § 103, jointly or alternatively, the burden of
proof is the same, and its fairness is evidenced by the PTO' s inability to
manufacture products or to obtain and compare prior art products." In re
Best, 562 F.2d 1252, 1255 (CCPA 1977). That is, once the Examiner has
provided a reasonable basis for inherency, the burden is placed on
Appellants to rebut that position with evidence, not attorney argument.
At best, Appellants have recognized new properties that inherently
result from administration of the cyclized CGQRETPEGAEAKPWYC
6 Chenling Xiong et al., The lectin-like domain of TNF protects from
listeriolysin-induced hyperpermeability in human pulmonary microvascular
endothelial cells - A crucial role for protein kinase C-a inhibition, 52
VASCULAR PHARMACOLOGY 207-13 (2010).
7 Shabbir et al., Mechanism of Action of Novel Lung Edema Therapeutic
AP301 by Activation of the Epithelial Sodium Channel, 84 MOLECULAR
PHARMACOLOGY 899-910 (2013).
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Application 14/201, 119
peptide to ARDS patients to "prevent ... pulmonary edema" (FF 1 ), but
Appellants have "done nothing more than recognize properties inherent in
certain prior art ... just like the corrosion resistance properties inherent to
the prior art alloy in Titanium Metals." In re Cruciferous Sprout Litig., 301
F.3d 1343, 1350-51 (Fed. Cir. 2002) (citing Titanium Metals Corp. v.
Banner, 778 F.2d 775 (Fed. Cir. 1985). Therefore, even if Appellants have
recognized something about the peptide that was not known before, the
claims "do not describe a new method." Id. at 1352.
Appellants contend
The method of the present invention is based on the surprising
and unexpected result that TIP can be internalized, and that the
internalization of TIP leads to the intracellular phosphorylation
of the Myosin Light Chain in cells that have not been changed
by edema, thereby preventing passage of liquid into the alveoli
by increasing the expression of epithelial sodium channel and
inhibiting the activation of Protein Kinase C in the endothelium
of the capillaries.
(App. Br. 15).
We find this argument unpersuasive because unexpected results, a
type of secondary consideration, are not an element of an anticipation
analysis. See Cohesive Techs., Inc. v. Waters Corp., 543 F.3d 1351, 1364
(Fed. Cir. 2008) ("[S]econdary considerations are not an element of a claim
of anticipation").
Conclusion of Law
A preponderance of the evidence of record support the Examiner's
conclusion that Lucas teaches "prevention of edema" using the claimed
peptide as required by claim 1.
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Application 14/201, 119
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 102(b) as anticipated by Lucas. Claims 6 and 13 fall with claim 1.
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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