Ex Parte Wang

Patent Trial and Appeal Board

Jan 18, 2018

11127438 (P.T.A.B. Jan. 18, 2018)

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.
11/127,438 05/11/2005 Yi Wang AXJ-102CPRCE3 5259
133485 7590 01/22/2018
Nelson Mullins Riley & Scarborough LLP/Alexion
One Post Office Square
30 th Floor
Boston, MA 02109-2127
EXAMINER
GAMBEL, PHILLIP
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
01/22/2018 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):
ipboston.docketing@nelsonmullins.com
chris. schlauch @nelsonmullins.com
ipqualityassuranceboston@nelsonmullins.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YI WANG 1
Appeal 2017-003979
Application 11/127,438
Technology Center 1600
Before JOHN G. NEW, RICHARD J. SMITH, 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 an aerosol composition. Claims 15—17, 58, and 59 are on
appeal as rejected under 35 U.S.C. § 103(a).2 We have jurisdiction under 35
U.S.C. § 6(b).
We affirm-in-part.
1 Appellant identifies the Real Party in Interest as “Alexion Pharmaceuticals,
Inc.” Br. 2.
2 Appellant identifies “[t]he present application is a continuation-in-part of
U.S. Patent Application Number: 10/655,861, which is currently under
Appeal (Appeal No: 2016-000567).” Br. 2.
Appeal 2017-003979
Application 11/127,438
STATEMENT OF THE CASE
The Specification states:
Effective delivery to a patient is a critical aspect of any
successful drug therapy. Various routes of delivery exist, and
each has its own advantages and disadvantages. Oral drug
delivery of pills, capsules, elixirs, and the like is perhaps the most
convenient method, but many drugs are degraded in the digestive
tract before they can be absorbed. Subcutaneous injection is
frequently an effective route for systemic drug delivery,
including the delivery of proteins, but enjoys a low patient
acceptance. Since injection of drugs one or more times a day can
frequently be a source of poor patient compliance, a variety of
alternative routes of administration have also been developed,
including transdermal, intranasal, intrarectal, intravaginal, and
pulmonary delivery. Thus, it is desirable to improve drug
delivery methods and compositions, particularly for antibody-
based therapeutics in treating or preventing pulmonary diseases.
Spec. 1:18—27. The Specification further states:
Accordingly, this application provides compositions and
methods suitable for delivering antibody-based therapeutics.
These antibody-based therapeutics can be particularly useful in
preventing or treating pulmonary diseases or conditions such as
for example asthma. Examples of antibodies useful in this
application include anti-C5 antibody or antibodies that inhibit
activation of the complement cascade, for example, the
antibodies as described in U.S. Patent No. 6,355,245 [Evans].
Id. 2:2-7.
Claims 15 and 59 are independent claims, are representative, and are
reproduced below:
15. An aerosol composition comprising h5Gl.l at a
concentration of 30 mg/mL.
59. An aerosol composition comprising h5Gl.l at a
concentration of 30 mg/mL, about 10 mM sodium phosphate,
about 150 mM NaCl, and a surfactant.
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Application 11/127,438
Br. 22 (Claims App’x).
The following rejections are on appeal:
Claims 15—17, 58, and 59 stand rejected under 35 U.S.C. § 103(a)
over Evans,3 Fung 107,4 Fung 468,5 Fobb,6 Fi,7 Konteatis,8 West,9
Babington,10 Balu,* 11 Mak,12 Grayer,13 and Salfeld.14 Non-Final Action 12.15
Claims 15—17, 58, and 59 stand rejected under 35 U.S.C. § 103(a)
over Krause,16 Evans, Fung 107, Fung 468, West, Babington, Fobb,
Winter,17 Balu, Mak, Gahyer, and Salfeld. Id. at 16.
FINDINGS OF FACT
Except as otherwise indicated herein, we adopt the Examiner’s
findings of fact, reasoning on scope and content of the claims and prior art,
and conclusions set out in the Non-Final Action and Examiner’s Answer.
See Non-Final Action 2—20 and Answer 3—32. The findings of fact set forth
below are provided to highlight certain evidence.
3 US 6,355,245 B1 (issued Mar, 12, 2002) (“Evans”).
4 US 6,956,107 B2 (issued Oct. 18, 2005) (“Fung 107”).
5 US 6,998,468 B2 (issued Feb. 14, 2006) (“Fung 468”).
6 US 5,871,734 (issued Feb. 16, 1999) (“Fobb”).
7 US 2001/0036650 A1 (pub. Nov. 1, 2001) (“Fi”).
8 US 5,614,370 (issued Mar. 25, 1997) (“Konteatis”).
9 US 7,071,299 B2 (issued July 4, 2006) (“West”).
10 US 4,228,795 (issued Oct. 21, 1980) (“Babington”).
11 US 2007/0173444 A1 (pub. July 26, 2007) (“Balu”).
12 US 2002/0182260 A1 (pub. Dec. 5, 2002) (“Mak”).
13 US 2010/0104563 A1 (pub. Apr. 29, 2010) (“Ghayer”).
14 US 2009/0175857 A1 (pub. July 9, 2009) (“Salfeld”).
15 Non-Final Office Action mailed Oct. 7, 2015.
16 US 2004/0014782 A1 (pub. Jan. 22, 2004) (“Krause”).
17 US 5,648,260 (issued July 15, 1997) (“Winter”).
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Application 11/127,438
FF1. Evans discloses, “[t]he use of anti-C5 antibodies, e.g.,
monoclonal antibodies, to treat glomerulonephritis . . . and other
inflammatory conditions involving pathologic activation of the
complement system” and, further, “[t]he invention also relates to
compositions comprising native monoclonal antibodies (mAbs)
specific to human complement component C5 that block complement
hemolytic activity and C5a generation.” Evans Abstr., 1:20-23; see
also Non-Final Action 12, 14—16 and Answer 13—14, 26—27, 30, 32
(discussing Evans).
FF2. Evans discloses:
The method of the invention involves the use of
preparations containing antibodies to human complement
component C5 as pharmaceutical agents. More particularly, the
invention provides for the use of anti-C5 antibodies that bind to
complement component C5 or active fragments thereof.
Preferably, the antibodies block the generation and/or activity of
complement components C5a and C5b. For most applications,
the antibody is a monoclonal antibody.
. . . [And,] it is believed that the anti-C5 antibodies have
these and other therapeutic effects through their activity in
blocking the generation or activity of the C5a and/or C5b active
fragments of complement component C5. Through this blocking
effect, the antibodies inhibit the proinflammatory (anaphyla-
toxic) effects of C5a and the generation of the C5b-9 membrane
attack complex (MAC). Significantly, the blockage effected by
the anti-C5 antibodies, since it occurs at the level of complement
component C5, has the advantage of maintaining important
opsonic, anti-infective, and immune complex clearance
functions of the complement system mediated by, inter alia,
complement component C3.
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. . . [And,] [tjhese antibodies are useful for the treatment
of GN [glomerulonephritis] as well as a number of other
conditions.
Evans 7:6-44; see also Non-Final Action 12, 14—16 and Answer 13—
14, 26—27, 30, 32 (discussing Evans).
FF3. Evans discloses, “the most preferred antibody of the
invention [is] the 5G1.1 antibody.’ '’ Evans 7:62—63 (emphasis added);
see also Non-Final Action 12, 14—16 and Answer 13—14, 26—27, 30,
32 (discussing Evans).
FF4. West discloses that inhibiting the complement system
may be beneficial for treatment of, inter alia, asthma and that
humanized monoclonal antibodies to C5 were known and, further,
teaches administering complement Cls inhibitor peptide or
polypeptide via oral, mucosal membrane, pulmonary, transcutaneous,
intranasal routes of administration, where inhalant administration
can be by dry-powder, liquid aerosol, or nebulization. West 2:19-21,
32:16—38; see also Non-Final Action 8, 11—12, 15—17 and Answer 14,
19, 31—32 (discussing West).
FF5. Balu is directed to administering peptides to patients to
treat asthma by interacting with interleukin 5 receptors and discloses
that the administration can be via inhalation of an aerosol composition
having, preferably up to 30 mg/mL of the active compound in
suspension, solution, or dry powder. Balu ^fl[ 2, 7—10, 141—151; see
also Non-Final Action 12—13, 16, 18—19 and Answer 29-30
(discussing Balu).
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FF6. Further to the preceding finding of fact, Mak is directed
to treating patients by administering inflammation modifiers to reduce
or eliminate inflammation caused by cosmetics or skin care products
or to enhance wound healing but, like Balu, teaches an aerosol
formulation, including suspensions, dry powder compositions, and
solutions, and discloses such a composition preferably has up to 30
mg/mL of the pharmacological agent. Mak Abstr., 1113; see also
Non-Final Action 12—13, 16, 18 and Answer 29 (discussing Mak).
FF7. Krause discloses, “[sjtudies in animal models have
implicated both IgE and the complement system (and C5a in
particular) in airway hyperresponsiveness and asthma pathogeneisis.”
Krause 17; see also Non-Final Action 16—17 and Answer 4, 15, 21—
22, 24—27 (discussing Krause).
FF8. Krause discloses:
Harmful inflammation typically involves the pathogenic
activation of the complement system, and in particular the C5a
anaphylatoxin. C5a, a 74 amino acid peptide, is a complement
component generated early in the terminal phase of the
complement cascade by the proteolytic cleavage (by C5
convertase) of the complement component plasma protein C5,
and is itself a plasma protein and a key mediator of inflammation.
C5a promotes both vascular and cellular inflammatory
responses; it has both anaphylatoxic (e.g., bronchoconstricting
and vascular spasmogenic) and chemotactic effects
and
Considerable experimental evidence has demonstrated the
presence of increased levels of C5a in a number of autoimmune
diseases and inflammatory disorders. In addition, anti-C5
antibodies also been used to treat glomerulonephritis, a disease
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Application 11/127,438
characterized by inflammation of the kidney (see U.S. Pat. No.
6,355,245 [Evans]).
Krause H 4, 19; see also Non-Final Action 16—17 and Answer 4, 15,
21—22, 24—27 (discussing Krause).
FF9. Krause discloses, “[ajntibodies that bind to C5 and
inhibit the conversion of C5 to C5a (and C5b) by C5 convertase have
been shown to be effective in reducing symptoms of rheumatoid
arthritis in animal models of arthritis.” Krause 117; see also Non-
Final Action 16—17 and Answer 4, 15, 21—22, 24—27 (discussing
Krause).
FF10. Krause teaches and suggests administering “an anti-C5
monoclonal antibody (such as eculizumab [h5Gl.l] or
pexelizumab)” “for the treatment of respiratory diseases, such as...
asthma.” Krause H 206-07, 227 (emphasis added); see also Br. 5
(confirming that eculizumab is h5Gl.l or 5G1.1); see also Non-Final
Action 16—17 and Answer 4, 15, 21—22, 24—27 (discussing Krause).
FF11. Krause discloses “[ajsthma is most commonly treated
with oral and inhaled bronchodilators,” and teaches an agent of its
invention, e.g., the h5Gl.l antibody, can be “prepared as an inhaled
formulation, an inhaler, nebulizer, or other device for inhalation” and
as an “inhalation formulations ... as powders and aerosols.” Krause
11 10, 207, 281, 298—99; see also Non-Final Action 16—17 and
Answer 4, 15, 21—22, 24—27 (discussing Krause).
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DISCUSSION
In analyzing patentability and determining obviousness “[t]he
combination of familiar elements according to known methods is likely to be
obvious when it does no more than yield predictable results.” KSR Int 7 Co.
v. Teleflex Inc., 550 U.S. 398, 416 (2007). “[W]hen the question is whether
a patent claiming the combination of elements of prior art is obvious,” the
answer depends on “whether the improvement is more than the predictable
use of prior art elements according to their established functions.” Id. at
417. “If a person of ordinary skill can implement a predictable variation [of
a known work], § 103 likely bars its patentability.” Id. “For the same
reason, if a technique has been used to improve one device [or process], and
a person of ordinary skill in the art would recognize that it would improve
similar devices [or processes] in the same way, using the technique is
obvious unless its actual application is beyond his or her skill.” Id. “[A]
prior art printed publication cited by an examiner is presumptively enabling
barring any showing to the contrary by a patent applicant.” In re Antor
Media Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012).
The obviousness analysis “can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ.” KSR,
550 U.S. at 418. “A person of ordinary skill is also a person of ordinary
creativity, not an automaton.” Id. at 421. “In determining whether the
subject matter of a patent claim is obvious, neither the particular motivation
nor the avowed purpose of the patentee controls. What matters is the
objective reach of the claim. If the claim extends to what is obvious, it is
invalid under § 103.” Id. at 419.
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Application 11/127,438
Finally, “apparatus [or composition] claims cover what a device [or
composition] is, not what a device [or composition] does.'” Hewlett-Packard
Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1468 (Fed. Cir. 1990). “[T]he
patentability of apparatus or composition claims depends on the claimed
structure, not on the use or purpose of that structure.” Catalina Marketing
Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002).
Obviousness over Evans, Fung 107, Fung 468, Lobb, Li, Konteatis,
West, Babington, Balu, Mak, Ghayer, and Salfeld
We find, in view of the above-cited precedent and noted findings of
fact, the Examiner established a prima facie case that claims 15—17 and 58
would have been obvious. Without discounting the relevant teachings of the
other cited prior art, Evans discloses the claimed antibody, i.e., h5Gl.l, and
suggest that it is useful as a therapy for conditions caused by the C5a and
C5b-9 components cleaved from C5. FF1—FF3. Further, West teaches and
suggests that antibodies or peptides can be administered for inhalation as an
aerosol. FF4. Moreover, Balu and Mak teach that, generally, aerosol
compositions (for treating asthma or for other therapies) should preferably
have up to 30 mg/mL of a pharmacological agent, e.g., a peptide. FF5—FF6.
Based on the above-referenced and other findings of fact determined by the
Examiner and identified in the Non-Final Action and Answer, we conclude
that the composition of claims 15—17 and 58 is taught and suggested by the
cited prior art combination, that there would have been motivation to make
the cited prior art combination to achieve the claimed invention, and that
there would have been a reasonable likelihood of successfully doing so
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Application 11/127,438
because doing so amounted to the predictable use of prior art elements
according to their established functions.
Regarding claim 59, Appellant argues “none of the references teach or
suggest the particular aerosol composition recited in claim 59 (i.e.,
comprising h5Gl. 1 at a concentration of 30 mg/mL, about 10 mM sodium
phosphate, about 150 mMNaCl, and a surfactantBr. 10 (emphasis
added). While the claim elements covering the antibody and its
concentration (and likely also NaCl and its concentration, optimized for
osmolarity) would have been obvious over the prior art combination, e.g.,
Balu and Mak, as discussed above, the Examiner cited the disclosures of
Ghayer and Salfeld as teaching or suggesting the sodium phosphate
concentration and surfactant elements of claim 59. We find the evidence of
record does not establish that these elements of claim 59 would necessarily
have been obvious over these references in combination with the other cited
art.
The relevant disclosures of Ghayer and Salfeld are similar. See Gayer
1 55 and Salfeld 1 579. Each reference discloses a pharmaceutical
composition having ranges of components covering 30 mg/m I. of antibody,
10 mM sodium phosphate, 150 mM NaCl, and a surfactant. Id. However,
these prior art pharmaceutical compositions are disclosed as being “suitable
for parenteral administration,” which has not been established as equivalent
to inhalant administration and there is no evidence identified by the
Examiner that the concentrations of components of one type of
pharmaceutical composition can be extrapolated to those of the other. For
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this reason, we conclude a prima facie case for obviousness has not been
established for claim 59.
Returning to the other claims on appeal, Appellant argues the claims
are non-obvious because there was a lack of clarity in the relevant art as of
the invention date as to the role of C5 in airway diseases, such as asthma.
Br. 6—8 (citing Karp18 and Humbles19). Appellant argues Karp is evidence
that there was no reason to pursue anti-C5 antibody therapy to treat asthma
and that the reference, in fact, teaches away from such therapy because it
discloses that inhibition of C5aR reduced IL-12, and IL-12 is evidenced to
mitigate allergic asthma in experimental testing, ergo, inhibiting C5aR may
worsen allergic asthma. Id. at 6. Appellant also argues Humbles is evidence
that reduction in C3aR, which is upstream in the complement cascade from
C5, C5a, and C5aR, is shown to mitigate asthma and, therefore, the skilled
artisan would have no reason to look to these downstream components for
an asthma treatment. Id. at 7.
This argument is not persuasive. As an initial matter, the claims do
not require treatment of asthma with the claimed h5Gl. 1 antibody, they
merely require an aerosol composition comprising it. Thus, Appellant’s
contentions regarding uncertainty about the role of C5a (or C5) in asthma or
its treatment is largely irrelevant, except to the extent that the cited prior art
relates to subject matter touching on this issue and the use of anti-C5
18 Christopher L. Karp et al., Identification of Complement Factor 5 as a
Susceptibility Locus for Experimental Allergic-asthma, 1 Nat. Immunology
221-26 (2000) (“Karp”).
19 Alison A. Humbles et al., A Role for the C3a Anaphylatoxin Receptor in
the Effector Phase of Asthma, 406 Nature 998—1001 (2000) (“Humbles”).
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Application 11/127,438
antibodies as asthma therapy and therapy for other complement system
inflammation-related conditions.
Furthermore, in Medichem, our reviewing court explained that
“[w]here the prior art contains ‘apparently conflicting’ teachings (i.e., where
some references teach the combination and others teach away from it) each
reference must be considered ‘for its power to suggest solutions to an artisan
of ordinary skill. . . considering] the degree to which one reference might
accurately discredit another.’” Medichem, S.A. v. Rolabo, S.L., 437 F.3d
1157, 1165 (Fed. Cir. 2006) {quoting In re Young, 927 F.2d 588, 591 (Fed.
Cir. 1991)). Further, “[ojbviousness does not require absolute predictability
of success ... all that is required is a reasonable expectation of success.'1'’ In
re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009). The “case law is clear that
obviousness cannot be avoided simply by a showing of some degree of
unpredictability in the art so long as there was a reasonable probability of
success.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007).
Here, we conclude that, while there is some evidence that inhibiting
C5 might, theoretically, worsen asthma (see Karp),20 the balance of evidence
(FF1—FF6) establishes that the skilled artisan would have pursued an aerosol
20 Humbles, unlike Karp, does not support Appellant’s contentions.
Humbles discloses research into the relevance of C3a/C3aR to allergic
asthma and identifies that C5a is well defined as involved in allergic disease
Humbles 998. ft is not clear from Humbles that Appellant’s argument, i.e.,
“Humbles clearly would have led one of ordinary skill in the art to believe
that complement factors (e.g., C3a) upstream of C5a are involved in airway
hyperresponsiveness, and thus that inhibition of C5a alone would not be
effective to prevent the condition,” is supported by the reference. Br. 7. In
any event, the claims relate to an anti-C5 antibody therapy, not an anti-C5a
antibody therapy.
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composition, anti-C5 antibody therapy, using h5Gl.l, to treat asthma and
would have had a reasonable expectation of successfully doing so based on
the teachings of the prior art.
Appellant argues there would have been no reasonable expectation of
success in formulating h5Gl.l in an aerosol composition. Br. 10 (Appellant
also argues over claim 59, which we addressed, supra). Appellant contends
the submitted evidence establishes that developing a protein-based, aerosol
formulation was challenging (citing Cleland)21 and would be expected to
result in a formulation that lacked efficacy (citing Fahy),22 such that the
skilled artisan would choose to use a dry powder formulation rather than an
aerosol formulation (citing Maa).23 Id. at 11—12. Appellant contends that
the development of inhalation formulations for biotherapeutics lagged
behind other types of formulations for these reasons. Id. at 12 (citing
Mack)24.
This argument is not persuasive. As discussed above, when the art
includes conflicting disclosures the evidence must be weighed and, also,
absolute predictability is not required to show obviousness. Medichem, 437
21 Jeffrey L. Cleland et al., The Development of Stable Protein
Formulations: A Close look at Protein Aggregation, Deamidation, and
Oxidation, 10 Critical Rev. Therapeutic Drug Carrier Sys. 307-77
(1993) (“Cleland”).
22 John V. Fahy et al., Effect of Aerosolized Anti-IgE (E25) on Airway
Responses to Inhaled Allergen in Asthmatic Subjects, 160 Am. J. Respir.
Crit. Care Med. 1023-27 (1999) (“Fahy”).
23 Yuh-Fun Maa et al., Protein Inhalation Powders: Spray Drying vs Spray
Freeze Drying, 16 Pharmaceutical Research 249-54 (1999) (“Maa”).
24 Peter Mack et al., Particle engineering for inhalation formulation and
delivery of biotherapeutics, Inhalation (2012) (“Mack”).
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F.3d at 1165; Kubin, 561 F.3d at 1360; and Pfizer, 480 F.3d at 1364.
Cleland is directed to the challenging nature of producing stable protein
pharmaceutical formulations, but states, “[predicting a priori the alteration
of pharmaceutical properties caused by the three degradation routes is
difficult, and must be determined on a case-by-case basis for each protein.”
Cleland 307. The evidence of record supports that a stable protein-based,
e.g., h5Gl.l antibody, aerosol could be produced. FF3—FF6; see also FF10-
FF11 (Krause teaching and suggesting administering h5Gl.l antibodies in
an aerosol formulation). Maa discloses dry powder-based protein
pharmaceutical formulations and compares drying by spraying and drying by
spray freezing; however, it is not clear that the reference supports
Appellant’s contention that this was a common choice in lieu of liquid
aerosol formulations. And, Fahy discloses that the antibody E25, an anti-
IgE antibody, did not effectively treat asthma; however, Fahy makes no
mention of h5Gl.l antibodies (or any anti-C5 antibody) nor indicates such
would be ineffective to treat any condition. Finally, while Mack also
identifies that protein-based inhalation products presented challenges, it does
not contradict the Examiner’s cited prior art, which suggests an aerosol
composition comprising h5Gl. 1 could be produced. We also note that
Appellant’s Specification does not describe any way of producing such an
aerosol composition indicated to specifically overcome the uncertainties and
instability issues Appellant now urges were understood to have been barriers
to producing and effectively using the invention. Therefore, we conclude
the balance of evidence supports the Examiner’s determination of
obviousness as to claims 15—17 and 58.
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For the reasons above, we affirm this obviousness rejection as to
claims 15—17 and 58 and reverse it as to claim 59.
Obviousness over Krause, Evans, Fung 107, Fung 468, West,
Babington, Lobb, Winter, Balu, Mak, Ghayer, and Salfeld
This obviousness rejection includes the prior art combination of
Evans, West, Balu, and Mak, which we discussed above in relation to the
first obviousness rejection as supporting the Examiner’s prima facie case for
obviousness. Further, for this rejection the Examiner also adds Krause,
which discloses treating asthma by blocking the cleavage of C5 into C5a
(and C5b) by administering eculizumab, i.e., h5Gl.l antibodies. FF7—FF10.
Furthermore, Krause teaches and suggests administering the claimed
antibodies via an inhalation formulation by inhaler, nebulizer, or other
device, as an aerosol. FF11. Therefore, for the same reasons discussed
above with respect to the first obviousness rejection and also because of the
highly relevant disclosure of Krause, we conclude the Examiner established
a prima facie case that claims 15—17 and 58 would have been obvious.
Appellant argues that, although Krause discloses using the antibody
eculizumab (i.e., the claimed h5Gl.l antibody) to treat inflammatory
diseases, the reference does so only in a “laundry list of other well-known
putative anti-arthritic agents,” and, therefore, “the reference does not
expressly or inherently disclose aerosol compositions of h5Gl.l at a
concentration of 30 mg/mL, let alone compositions comprising 10 mM
sodium phosphate, about 150 mM NaCl, and a surfactant as instantly
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claimed.” Br. 14—15. Appellant cites Neurogen25 as reporting that a clinical
trial focused on asthma treatment with a small molecule C5a antagonist (i.e.,
NGD 2000-1) failed and argue this supports the non-obviousness of the
claims over Krause. Id. at 16.
Appellant also renews the argument that the prior art was conflicted
over whether C5 had a role in treating asthma, citing Karp and Humbles,
contending that even though the prior art references, like Krause, identify
that anti-C5 antibodies, like h5Gl.l, can inhibit the production of C5a (and
C5b), which the references identify as contributing to asthma, the prior art
teachings in this regard cannot surmount the contrary teachings of Karp and
Humbles. Id. at 15.
These arguments are not persuasive with respect to claims 15—17 and
58. “Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. . . . [The references] must be read, not in
isolation, but for what [they] fairly teach[] in combination with the prior art
as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Here, the rejection is based on a combination of prior art and attacking
Krause individually is not persuasive. The argument regarding Karp and
Humbles remains unpersuasive, as discussed above regarding the first
obviousness rejection. Further, Neurogen might have dissuaded the skilled
artisan from attempting to treat asthma with the small molecule
25 Neurogen Corporation, Neurogen Reports Phase Ila Clinical Trial Results
for Oral Asthma Drug, Press Release, http://www.highbeam.com/doc/lGl-
131552788.html (2004), indicated as visited July 14, 2011 (“Neurogen”)
(internet address provided on the exhibit is not active).
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NGD 2000-1, administered orally, but this is not necessarily relevant to
treating asthma with an h5Gl. 1 antibody administered via aerosol or to the
claimed aerosol composition comprising h5Gl.l, for which an intended use
is not determinative of patentability.
However, regarding claim 59, this argument is persuasive. We
conclude Krause does not remedy the deficiencies identified with respect to
the first obviousness rejection. Ghayer and Salfeld are again relied on by the
Examiner in rejecting claim 59, but, as discussed above, they do not teach or
suggest that the sodium phosphate and surfactant limitations of claim 59
would have been obvious, at least not in an aerosol composition.
Returning to claims 15—17 and 58, Appellant also argues that anti-C5
antibodies and C5a inhibitors are not equivalent and that the Examiner’s
rejection, to the extent premised on such equivalence, is in error. Br. 18.
Relating to this, Appellant contends anti-C5 antibodies are superior in
treating asthma compared to anti-C5a antibodies and cites the Wang
Declaration26 as support.
This argument is not persuasive. The claims are directed to “[a]n
aerosol composition comprising h5Gl.l,” not an asthma treatment, and the
prior art teaches and suggests an aerosol composition comprising this anti-
05 antibody. The equivalency of C5 and C5a in relation to causing or
treating asthma is not of significance in view of the prior art references,
which teach using an aerosol composition of h5Gl.l to inhibit the
conversion of C5 into its C5a and C5b components to treat inflammatory
26 Declaration under 37 CFR § 1.132 of Yi Wang (dated Mar. 6, 2014)
(“Wang Decl.”).
17
Appeal 2017-003979
Application 11/127,438
related diseases, such as asthma. The record does not support that the
Examiner has premised the obviousness rejection on the equivalence of C5
and C5a inhibition/effects.
Further, we note that, while the Wang Declaration identifies that a
therapy using anti-C5 antibodies was superior in some respects to a therapy
using anti-C5a antibodies in treating asthma, neither the Wang Declaration
nor the Appellant’s Brief states that these results would have been
unexpected or surprising to the skilled artisan at the time of the invention as
compared the closest prior art.
For the reasons above, we affirm the obviousness rejection with
respect to claims 15—17 and 58 and reverse it with respect to claim 59.
SUMMARY
The obviousness rejections are each affirmed with respect to claims
15—17 and 58 and reversed with respect to claim 59.
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-IN-PART
18