Ex Parte Cook

Patent Trial and Appeal Board

Apr 26, 2017

12895566 (P.T.A.B. Apr. 26, 2017)

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
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/895,566 09/30/2010 Robert Cook MICRODOSE 09.04 7996
27667 7590
HAYES SOLOWAY P.C.
4640 E. Skyline Drive
TUCSON, AZ 85718
EXAMINER
HAGHIGHATIAN, MINA
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
04/28/2017 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ROBERT COOK1
Appeal 2016-001872
Application 12/895,566
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, and DAVID COTTA,
Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating Raynaud’s phenomenon by administering a calcium channel
blocker in dry powder form. The Examiner rejects the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 According to Appellant, the Real Party in Interest is Microdose
Therapeutx, Inc. and Teva Pharmaceutical Industries Ltd. Appeal Br. 1.
Appeal 2016-001872
Application 12/895,566
STATEMENT OF THE CASE
Claims 1, 5—7, 9, 15, 20, 21, and 23 are on appeal, and can be found in
the Claims Appendix of the Appeal Brief. Claim 1 is representative of the
claims on appeal, and reads as follows:
Claim 1: A method for treatment of Raynaud’s Phenomenon
comprising delivering directly to a patient’s lungs, on an as-
needed basis, in unit dose amounts of between about 0.1 and 50
milligrams, a systemically effective amount of a calcium channel
blocker in dry powder form, wherein the calcium channel blocker
comprises clevidipine, wherein the dry powder calcium channel
blocker has a median powder size of 0.5-10 microns, and wherein
a total 1 to 10 unit doses of the calcium channel blocker are
delivered per day.
Claim 15, the only other independent claim, is similarly
directed to a method of treating Raynaud’s phenomenon using a
calcium channel blocker selected from clevidipine or nicardipine in a
dry powder form.
Appellant requests review of the Examiner’s rejection of claims 1, 5—
7, 9, 15, 20, 21, and 23 under 35 U.S.C. § 103(a) as obvious over Krishna2 in
view of Andersson,3 Fritschi4 or Maguire,5 and as evidenced by Newman,6
and further in view of Crockford.7
2 Krishna et al., US 2010/0105743 Al, published Apr. 29, 2010 (“Krishna”).
3 Andersson et al., US 5,856,346, issued Jan. 5, 1999 (“Andersson”).
4 Fritschi, US 4,605,552, issued Aug. 12, 1986.
5 Maguire et al., WO 2008/156820 Al, published Dec. 24, 2008
(“Maguire”).
6 Newman, Aerosol Deposition Considerations in Inhalation Therapy, 88
Chest 152S-160S (1985).
7 Crockford et al., US 2005/0087189 Al, published Apr. 28, 2005
(“Crockford”).
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Application 12/895,566
As Appellant does not argue the claims separately (see Appeal Br.
20), we focus our analysis on independent claims 1 and 15, and claims 5—7,
9, 15, 20, 21, and 23 stand or fall with those claims. 37 C.F.R. § 41.37
(c)(l)(iv).
Obviousness
The Examiner finds that Krishna teaches “pharmaceutical
compositions comprising clevidipine,” which is known to be “a fast acting
dihydropyridine calcium channel blocking agent.” Final Act. 3 (emphasis
omitted). Krishna lists diseases, such a Raynaud’s phenomenon that can be
treated with a calcium channel antagonist. Final Act. 4. The Examiner
acknowledges that Krishna “lack[s] specific disclosure on the active agent
being delivered to the lungs via inhalation and the specific amounts.
However dry powder inhalation of active agents such as calcium channel
blockers are known in the art and strongly suggested.” Final Act. 4.
The Examiner finds that Andersson teaches the use of “short-acting
calcium antagonists of the dihydropyridine type” such as nicardipine that are
used in a therapeutic dose range from 0.01—100 mg/h. Final Act. 4
(emphasis omitted); see Andersson 1:27—28.
The Examiner finds that Fritschi teaches “that calcium antagonists are
immediately effective upon inhalation administration and cause an
immediate increase in the blood flow in the coronary artery without exerting
an unfavorable influence on the periphery” and can be administered using a
dry powder inhaler. Final Act. 5 (emphasis omitted); see Fritschi 2:32—33.
Maguire teaches treating “disease associated with decreased skeletal
muscle blood flow [such as] Raynaud’s phenomenon or intermittent
claudication” using administration protocols that include inhalation. Final
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Act. 6 (emphasis omitted); see Maguire 29:13—29. Maguire’s “calcium
channel blockers include nicardipine, nifedipine and clevidipine.” Final Act.
7 (emphasis omitted).
The Examiner looks to Newman and Crockford for establishing that
dry powder inhalers were known and that inhalation therapy generally has
known advantages over intravenous administration. See Final Act. 8—9.
The Examiner concludes that based on the combined teachings it
would have been obvious to one of ordinary skill in the art to
treat Raynaud’s disease with clevidipine at therapeutically
effective amounts. Krishna et al also disclose the [sic]
clevidipine is sensitive to light and air, Andersson et al teach
pharmaceutical preparations of clevidipine in both liquid and
powder forms. Fritschi discloses that inhalable calcium agonists
[sic, antagonists] are advantageous in treating blood flow and/or
Maguire et al teach a method of treating Raynaud’s phenomenon
by administration of a therapeutically effective amount of a
calcium channel blocker by inhalation in a dry powder or
suspension form. Maguire et al also teach [sic] that said calcium
channel blockers include nicardipine, clevidipine, etc.
Accordingly, one of ordinary skill in the art having possession of
Krishna et al, Andersson et al and Fritschi or Maguire et aFs
teachings, would be well informed that Raynaud’s disease
(phenomenon) can be treated by a therapeutically effective
amount of calcium channel blockers such as clevidipine and that
the administration may be via an inhaler in the form of a dry
powder.
Final Act. 9—10.
Appellant acknowledges that Krishna “generically recite[s] that
clevidipine is an example of a calcium channel blocker that may be used to
treat a disease such as Raynaud’s disease.” Appeal Br. 12. Appellant,
however, contends that there is “no motivation whatsoever for one of
ordinary skill to deviate from the liquid emulsion compositions taught” in
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Krishna. Appeal Br. 13. Appellant contends that “Andersson’s teachings
[are] limited exclusively to administrations via injection” and does not
mention clevidipine. Appeal Br. 13. Although “the Fritschi reference [is
cited by the Examiner] for the alleged teaching of inhalation administration
of calcium antagonists^] Fritschi fails to mention either clevidipine or
nicardipine,” but instead teaches the use of “diltiazem [which] is a
nondihydropyridine and thus belongs to a different class of drugs.” Appeal
Br. 14. Appellant cites Exhibits A—D to establish that different calcium
channel blockers belong to different classes of drugs having different
structures. According to Appellant, “Maguire add[s] nothing to the already
deficient combination of Krishna, Andersson and Fritschi.” Appeal Br. 18.
The issue is: Does the preponderance of evidence of record support
the Examiner’s conclusion that the combination of references renders the
method of treating Raynaud’s phenomenon with clevidipine in an inhaled
powder form obvious?
Findings of Fact
FF1. Krishna teaches that “clevidipine is a fast acting dihydropyridine
calcium channel blocking agent” that can be applied to treating
conditions such as chest pain (angina), migraines, brain aneurysm
complications, irregular heartbeats (arrhythmia) and Raynaud’s
disease among others. Krishna 126.
FF2. “Clevidipine is typically formulated as a liquid emulsion suitable for
intravenous administration.” Krishna 139 and 149.
FF3. Maguire teaches that “Raynaud’s phenomenon is a disorder associated
with restricted blood flow to body extremities such as the fingers,
toes, ears and nose, and reflects an aberration of the normal response
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Application 12/895,566
to cold involving peripheral vasoconstriction and restriction of blood
flow to the extremities in order to protect the core body temperature.”
Maguire 4:3—7. Maguire teaches administering medicines to treat
“disease associated with decreased skeletal muscle blood flow.”
Maguire 8:13—15. “[T]he disease associated with decreased skeletal
muscle blood flow is Raynaud’s phenomenon or intermittent
claudication” and the medicaments can be administered via inhalation.
Maguire 9:10-13.
FF4. Maguire teaches that for inhalation the compounds “will generally
have a small particle size for example on the order of five (5) microns
or less” and can be administered in dry powder form. Maguire 29:15—
16.
FF5. Fritschi teaches that “calcium-antagonists are immediately effective
upon inhalational administration and cause an immediate increase in
the blood flow in the coronary artery without exerting an unfavorable
influence on the periphery.” Fritschi 1:35—40.
FF6. Andersson discloses the use of “very short-acting calcium antagonists
of the dihydropyridine type with high vascular selectivity.”
Andersson 1: 4—6. “Nicardipine, which is a calcium antagonist of the
dihydropyridine type, has high vascular selectivity and high potency,
but the effect duration is too long, as usually is the case for this class
of compounds.” Andersson 1: 38-42.
FF7. Newman teaches that inhalation therapy has well-established
advantages such as: lower drug dosage, rapid onset of action, and low
incidence of systemic side effects. Newman 152S.
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FF8. Crockford teaches the administration of drug using an inhaler. The
drug “passes into the holding chamber from a source of droplets or
particles, for example, a multi-dose inhaler (MDI) 3. The MDI 3
releases the liquid or powder drug in a cloud such that it loads the air
with the drug.” Crockford 129.
Principle of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Analysis
Claim 1
We have reviewed Appellant’s contentions that the Examiner erred in
rejecting claim 1 as obvious over the cited art. Appeal Br. 12—19. We
disagree with Appellant’s contentions and adopt the findings concerning the
scope and content of the prior art set forth in the Examiner’s Answer and the
Final Rejection dated May 26, 2005. For emphasis, we highlight and
address the following:
Appellant acknowledges that “Krishna teaches administration of a
liquid emulsion formulation of clevidipine by injection.” Reply Br. 5
(emphasis removed). But Appellant argues that there is “no motivation
whatsoever for one of ordinary skill to deviate from the liquid emulsion
compositions taught therein.” Appeal Br. 13.
We are not persuaded by Appellant’s contention. The test for
obviousness is what the combined teachings of the references as a whole
would have suggested to those of ordinary skill in the art. In re Keller, 642
F.2d 413, 425 (CCPA 1981). Here, the references of Krishna as well as
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Maguire teach the administration of a calcium channel blocker to treat
Raynaud’s phenomenon. FFlandFF3. Maguire also teaches that these
calcium channel blockers can be administered via inhalation. FF4. One of
ordinary skill in the art would appreciate “that inhalation therapy has well-
established advantages such as: lower drug dosage, rapid onset of action,
and low incidence of systemic side effects.” FF7. The Examiner finds that
the inhalation route of administration is also disclosed by Fritschi. “Fritschi
clearly discloses that it is surprisingly advantageous to administer calcium
agonists by inhalation.” Ans. 10; FF5. Taken as a whole, we agree with the
Examiner’s conclusion that it would have been obvious to one of ordinary
skill in the art at the time the invention was made to apply inhalation therapy
of calcium channel blockers to patients experiencing Raynaud’s
phenomenon because of the known advantages of administering products via
inhalation as opposed to oral or intravenous administration routes.
We are also not persuaded by Appellant’s contention that “Andersson
teaches away from the use of formulations comprising nicardipine.” Appeal
Br. 13. As explained by the Examiner, “merely disclosing properties of the
calcium antagonists which includes a long duration of effect for nicardipine”
as disclosed by Andersson “does not prevent it from being [useful] in dry
powder form.” Ans. 8; see FF6.
Appellant contends that “Fritschi fails to mention either clevidipine or
nicardipine” as calcium antagonist for inhalation therapy. Appeal Br. 14.
“[DJiltiazem is a nondihydropyridine and thus belongs to a different class of
drugs than clevidipine or nicardipine.” Id. (citing Exhibits A—D).
We find no error in the Examiner’s reliance on Fritschi for disclosing
that inhalation therapy is a suitable route of administering calcium channel
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blockers. The Examiner explains that “the rejection was not based on
structural similarities but functional similarities. In other words, the
references would have motivated one of ordinary skill in the art to have
prepared inhalable formulations comprising any calcium channel blocker for
easy and efficient administration/treatment.” Ans. 9.
Appellant contends that it is clear that the Examiner, using the present
application as a guide, has selected isolated features of the various relied-
upon references to arrive at the limitations of the claimed invention. See
Reply Br. 5, 7. We are not persuaded by Appellant’s argument because the
Examiner relies solely on knowledge shown to be within the skill of the
ordinary artisan and is not relying on information only available in
Appellant’s disclosure. See In re McLaughlin, 443 F.2d 1392, 1395 (CCPA
1971). Insofar as Appellant is arguing the number of references relied upon
by the Examiner in making the rejection, this too is not persuasive because it
is not the number of references but what the teaching of the references mean
to the ordinarily skilled artisan. See In re Gorman, 933 F.2d 982, 986 (Fed.
Cir. 1991) (affirming obviousness rejection over thirteen references and
stating that “[t]he criterion ... is not the number of references, but what they
would have meant to a person of ordinary skill in the field of the
invention.”).
We conclude that the evidence cited by the Examiner supports a prima
facie case of obviousness with respect to claim 1. Appellant has not
provided sufficient rebuttal evidence or evidence of secondary
considerations that when balanced with prima facie case renders the claim
unobvious. Claims 5—7 and 9 were not separately argued and fall with
claim 1. See Appeal Br. 20.
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Claim 15
Claim 15 is directed to a method for treating Raynaud’s phenomenon
by using calcium channel blockers that are administered with a device
“generating a cloud of said calcium channel blocker by vibrating the dry
powder with a vibrator coupled to the inhaler.”
Crockford teaches a multi-dose delivery device for dispensing liquid
or dry powder drug. The drug “passes into the holding chamber from a
source of droplets or particles, for example, a multi-dose inhaler (MDI) 3.
The MDI 3 releases the liquid or powder drug in a cloud such that it loads
the air with the drug.” Crockford 129. The feedback indicator in Crockford
“is a vibrator unit which vibrates gently during inhalation while drug-laden
air is delivered.” Id. 132. Crockford teaches that liquid medicaments can
be nebulized, i.e., made into a cloud form, using different types of
nebulizers. One such nebulizer has “a housing that has a reservoir which
holds a quantity of liquid to be dispensed, which housing has a perforated
membrane in contact with the reservoir and an ultrasonic vibrator connected
to the housing to vibrate the perforated membrane.” Id. | 55.
With respect to claim 15, Appellant contends that “Crockford fails to
teach that the vibrator generates the cloud by vibrating the dry powder.”
Appeal Br. 18.
We are not persuaded by Appellant’s contention. The Examiner
identified that Crockford teaches administering a dry powder medicament in
cloud form. See Ans. 6, 12. The Examiner finds that “[t]he step of
preparing/generating the dry powder by vibrating the dry powder is not the
critical step in achieving the claimed method. In other words, and as
disclosed in the specification and claims, any dry powder inhaler device can
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deliver the dry powder to the lungs and achieve the claimed method.” Ans.
12. We agree with the Examiner that the criticality appears to be with the
form of the medicine, specifically that it is in a dry powder cloud form, and
not with the way the form is generated. We also note that Crockford teaches
that an ultrasonic vibrator attached to a reservoir can generate a cloud of
medicine from a liquid. We see no reason that a similarly structured device
could not reasonably achieve the same result using a powder medicament in
the same chamber. Furthermore, the Examiner explains that such devices
for producing a cloud from a powdered medicament are “well known and
commonly used in the art and not of Appellant’s findings” and that the
claims are rendered obvious based on the combined teachings of the
references. Ans. 12. After all, the person having ordinary skill in the art is
presumed to have ordinary creativity and intelligence. KSR, 550 U.S. at 421.
We conclude that the evidence cited by the Examiner supports a prima
facie case of obviousness with respect to claim 15. Claims 20, 21, and 23
were not separately argued and fall with claim 15. See Appeal Br. 20.
SUMMARY
We affirm the rejection of claims 1, 5—7, 9, 15, 20, 21, and 23 under
35 U.S.C. § 103(a) as obvious over Krishna, Andersson, Fritschi, Maguire,
as evidenced by Newman and Crockford.
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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