Ex Parte Henriksen et al

Board of Patent Appeals and Interferences

Jan 30, 2009

10071505 (B.P.A.I. Jan. 30, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte INGRID HENRIKSEN, TORE OMTVEIT, VERA
KASPARKOVA, and ANNE KJERSTI FAHLVIK
____________

Appeal 2008-6236
Application 10/071,505
Technology Center 1600
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Decided:1 January 30, 2009
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Before RICHARD M. LEBOVITZ, FRANCISCO C. PRATS, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 CFR § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

Appeal 2008-6236
Application 10/071,505

DECISION ON APPEAL
This is a decision on appeal from the final rejection of claims 1, 3, 5-
7, 11, 12, and 19. Jurisdiction is under 35 U.S.C. § 6(b). We reverse the
rejection.

STATEMENT OF THE CASE
The claims are drawn to a method of administering a gas-containing
contrast agent to a subject. The method involves admixing a contrast agent
and a flushing medium and then administering the admixed product to a
subject over an infusion period of 5-60 minutes. According to the
Specification, the prior art administered contrast agents as a bolus over short
periods of 5-20 seconds (Spec. 2:4-14). The Specification discloses that
continuous infusion of the contrast agent over periods from 1 minute to 60
minutes minimizes “diagnostic artefacts [sic] such as shadowing and . . .
lengthen[s] the useful time window for imaging beyond the relatively short
duration of the backscatter signal peak resulting from passage of a contrast
agent bolus” (id. at 2:18-22). The Specification also teaches that using a
vertically positioned delivery vessel, such as a syringe, and an admixture of
contrast and flushing agents, improves homogeneity and delivery of the
contrast agent (Spec. 3:24 to 4:27).
Claims 1, 3, 5-7, 11, 12, and 19 are pending. Appellants appeal from
the Examiner’s final rejection of claims 1, 3, 5-7, 11, 12, and 19 under 35
U.S.C. § 103(a) as obvious in view of Unger et al. (US 6,033,645, Mar. 7,
2000) (Ans. 3). We select claim 1 as representative. Because Appellants do
not separately argue the patentability of the claims, claims 3, 5-7, 11, 12, and
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19 stand or fall with claim 1. 37 C.F.R. § 41.37(c)(vii)(1). Claim 1 reads as
follows:
1. A method of administering a gas-containing contrast agent
to a subject by continuous infusion, the improvement
comprising enhancing product homogeneity by controllably
delivering said gas-containing contrast agent from an upper
extremity of an essentially vertically positioned syringe and
admixing with a flushing medium prior to administration to the
subject, delivering the admixed product to the subject over an
infusion period of 5-60 minutes.

PRINCIPLES OF LAW
“During [patent] examination, the examiner bears the initial burden of
establishing a prima facie case of obviousness.” In re Kumar, 418 F.3d
1361, 1366 (Fed. Cir. 2005).
A patent may not be obtained though the invention is not
identically disclosed or described as set forth in section 102 of
this title, if the differences between the subject matter sought to
be patented and the prior art are such that the subject matter as a
whole would have been obvious at the time the invention was
made to a person having ordinary skill in the art to which said
subject matter pertains.
35 U.S.C. § 103(a) (2004).
Although common sense directs one to look with care at a
patent application that claims as innovation the combination of
two known devices according to their established functions, it
can be important to identify a reason that would have prompted
a person of ordinary skill in the relevant field to combine the
elements in the way the claimed new invention does. This is so
because inventions in most, if not all, instances rely upon
building blocks long since uncovered, and claimed discoveries
almost of necessity will be combinations of what, in some
sense, is already known.
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KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, ___, 127 S. Ct. 1727, 1741
(2007).
[T]he ultimate determination of obviousness “does not require
absolute predictability of success. ... [A]ll that is required is a
reasonable expectation of success.” In re O'Farrell, 853 F.2d
894, 903-904 (Fed. Cir. 1988); see also In re Longi, 759 F.2d
887, 897(Fed. Cir. 1985).
Brown & Williamson Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120,
1125 (Fed. Cir. 2000).
“[W]hen the PTO shows sound basis for believing that the products of
the applicant and the prior art are the same, the applicant has the burden of
showing that they are not.” In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990).

ISSUE
Does Unger describe or suggest “delivering” an “admixed product” of
a contrast agent and flushing medium to a subject “over an infusion period
of 5-10 minutes” as recited in claim 1?

FINDINGS OF FACT (FF)
Scope and content of the prior art
1. Unger describes gas filled vesicles which can serve as contrast agents in
diagnostic imaging techniques, such as ultrasound, computed tomography,
and magnetic resonance imaging (Unger, at col. 6, ll. 49-57; Ans. 3).
2. Unger states that, when the vesicles are administered to a subject via
injection, they pool or accumulate near the injection site (id. at col. 47, ll.
64-65).
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3. Unger states: “To promote the transport of the . . . vesicle composition
from the injection site into the bloodstream and, thereafter, to the region of
interest, a flush may be administered” (id. at col. 47, l. 65 to col. 48, l. 1).
4. “The flush may act, generally by mechanical action, to ‘push’ or ‘wash’
the injected compositions into the bloodstream” (id. at col. 48, ll. 1-3).
5. According to Unger,
the rate at which the lipid and/or vesicle compositions are
administered to a patient may have a profound effect on the
quality of the resulting diagnostic image. Specifically, it has
been found that the occurrence of diagnostic artifacts in
diagnostic images may be directly related to the rate at which
the lipid and/or vesicle compositions are administered. Thus, as
discussed above, the administration of a lipid and/or vesicle
composition at too high a rate can result in an excess
concentration of lipid and/or vesicle composition at the region
of interest. . . Conversely, the administration of a lipid and/or
vesicle composition at too low a rate can result in an
insufficient concentration of lipid and/or vesicle composition at
the region of interest. In the case of ultrasound imaging
involving, for example, gas filled vesicles, the application of
energy (sound waves) can result in too little sound energy being
reflected, thereby resulting, for example, in inadequate contrast
in the resulting ultrasound image.
(Id. at col. 44, ll. 40-60.)
6. Figure 1 of Unger shows a schematic representation of a system for
administering a contrast agent comprising a syringe 14 containing a contrast
agent and a mechanical injector 22 comprising a flush agent (id. at col. 49,
ll. 38-53). Unger’s Figure 2 shows a similar system with a syringe 14’
containing a contrast agent and a mechanical injector 22’. The “flush agent”
of Unger corresponds to the “flushing medium” of claim 1. See also Ans.
10-11.
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7. The syringe 14 and injector 22 are in flow contact with each other via a
conduit 26 which is adapted to administer the contrast agent and flush agent
to a patient (id. at col. 49, ll. 53-58; see Fig. 1). See also Ans. 10-11.
8. According to Unger
The flush agent 24' is desirably administered after
ejection of the contrast agent 20'. This generally involves
operation of the control means 42' to drive the mechanical
injector 22'. As with the embodiment discussed above, the
control means 42' controls the amount of power supplied to the
mechanical injector 22' and permits regulation of the rate at
which the mechanical injector 22' operates and, thereby, the
rate at which the flush agent 24' is ejected from the mechanical
injector 22'. The flush agent 24' is ejected from the mechanical
injector 22' and into and through the tubing 30' and the port 44.
The flush agent 24' serves to push or drive the contrast agent 20
from its location in the port 44 and/or the tubing 30',
throughout the length of the tubing 30', and into the patient. . . .
The flush may be stopped after contrast agent 20' has been
administered to the patient. Alternatively, the flush may be
continued so that the flush agent 24' is also injected into the
patient. The rate at which the mechanical injector 22' is
operated may be varied at any time during the ejection of the
flush agent 24', as desired.
(Id. at col. 51, ll. 35-56; as quoted on pages 10-11 of the Answer.)
9. Unger teaches several examples of administration periods for contrast
agent and flush followed by ultrasound imaging ((id. at col. 52, ll. 3-7):
Example 2: 2 second injection with contrast agent and 2 second flush
(id. at col. 52, l. 41-45). Unger describes the ultrasound image produced by
this regime as inferior (id. at col. 52, ll. 51-55).
Example 3: 5-10 second injection with contrast agent and 10-15
second flush (id. at col. 52, ll. 59-64). The image is described as “very
robust and long-lasting” (id. at col. 52, ll. 66-67).
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Example 4: 15 second injection with contrast agent and 10-15 second
flush (id. at col. 53, ll. 1-6). The image is described as “less robust” than
Example 3 (id. at col. 53, ll. 8-9).
Example 9 (prophetic): 50 second injection with contrast agent and 5-
10 minute flush (id. at col. 53, ll. 54-58).
Level of ordinary skill in the art
10. Persons of ordinary skill in the art had the technical skill to determine
the effective dosages and infusion periods over which to administer effective
dosages of contrast and flushing agent (id. at col. 44, l. 61 to col. 45, l. 53;
col. 45, l. 65 to col. 47, l. 21; Ans. 4-5).

ANALYSIS
The Examiner has the burden of establishing prima facie obviousness
of the claimed subject matter. In re Kumar, 418 F.3d at 1366. To meet this
burden, a reason must be provided as to why the differences between the
prior art and the claimed invention would have been obvious to persons of
ordinary skill in the art. 35 U.S.C. § 103(a) (2004); See KSR, 127 S. Ct. at
1741.
In this case, the Examiner contends that Unger describes the claimed
method of administering a gas-containing contrast agent by continuous
infusion, but does not “explicitly” teach the limitation of “delivering the
admixed product” of contrast agent and flushing medium “over an infusion
period of 5-60 minutes” as required by claim 1 (see Ans. 4). However, the
Examiner asserts that the claimed infusion period would have been arrived at
routinely when optimizing for “volume of the composition, gaseous vesicles,
type of encapsulation and other patient variable[s] such as age, area of
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interest, etc.” (id.). In reaching this conclusion, the Examiner provided
evidence from Unger that it was within the level of ordinary skill in the art to
determine the effective dosages and infusion periods over which to
administer effective dosages of contrast and flushing agent (FF10). The
Examiner also relied on Unger’s disclosure at column 51, lines 35-56 (FF8),
to meet the claimed limitation of “admixing” the contrast agent and flushing
agent prior to administration to the subject (see Ans. 10).
The Examiner has not met the burden of establishing prima facie
obviousness of the claimed subject matter. Claim 1 recites that an “admixed
product” of “contrast agent” and “flushing medium” is administered “over
an infusion period of 5-60 minutes.” The Examiner has not provided
adequate evidence that Unger’s disclosure would have suggested to persons
of ordinary skill in the art administration of an admixture comprising the
agent and flush for the claimed infusion period.
While Unger discloses that administration periods are routinely
determinable (FF10), in its examples, the contrast agent is administered from
about 2 to 50 seconds which is substantially less than the claimed infusion
period of 5-60 minutes (FF9). The Examiner contends that the claimed
period would have been arrived at by routine optimization taking into
account the factors ordinarily relied upon the skilled worker (Ans. 4; FF10).
However, the evidence of record militates against this conclusion.
Unger explicitly teaches that the rate of administration of the contrast
agent (gas filled vesicles) has “a profound effect on the quality of the
resulting diagnostic image” (FF5). Delivery at “too high a rate can result in
an excess of concentration” of the contrast agent “at the region of interest”
(id.). Delivery “at too low a rate can result in an insufficient concentration
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of lipid and/or vesicle composition at the region of interest” (id.).
Consistently, in the examples, Unger states that the image quality is low
when 2 and 15 second administration periods are utilized (FF9; Examples 2
and 4), but “very robust and long-lasting” for a 5-10 second intermediate
injection period (FF9; Example 3). While obviousness does not require
absolute predictability of success, there must be a reasonable expectation of
success. Brown, 229 F.3d at 1125. With teachings that (1) contrast agent
administration rate has a “profound” effect on image quality and (2) working
examples in which contrast agent is administered over seconds, not minutes,
the evidence does not support the Examiner’s position that it would have
been routine to vary contrast agent administration time several-fold in excess
over what is disclosed by Unger, and in doing so, there would have been a
reasonable expectation of success.
The Examiner also contends that Unger teaches admixing contrast
agent and flushing medium, relying on column 51, lines 35 to 56 of Unger
for this disclosure. Unger, in fact, teaches that the flush agent “serves to
push or drive the contrast agent” from the port or tubing and into the patient
(FF8; see also FF2-4). The flush is “administered after ejection of the
contrast agent” (FF8). While it may be correct that admixing occurs
between the contrast and flush agents, there is no explicit teaching in Unger
that this result takes place when the flush agent pushes the contrast agent
into the patient. Thus, the Examiner’s position appears to be that admixing
inherently takes place during Unger’s administration method. When a
rejection is based on inherency, the Examiner must provide a “sound basis”
for believing that the prior art accomplishes the same result which is
claimed. See In re Spada, 911 F.2d at 708.
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Here, the Examiner has not explained how Unger’s method would
result in administration of an admixture of contrast agent and flush agent for
an infusion period of 5-60 minutes as required by claim 1. The longest
infusion period explicitly described in Unger appears in Example 9 when a
50 second injection with contrast agent is followed by a 5-10 minute flush
(FF9; Unger, at col. 53, ll. 54-58). Even were an admixture to occur
between the contrast and flush agents as the latter was pushing the former
into the patient, the Examiner has not provided a sound basis for believing
that the admixture would be continuously administered for at least 5 minutes
of the flush period, a necessary condition to satisfy claim 1. Once the
contrast agent is pushed into the patient, the Examiner has not articulated a
reason for believing that portions of it would remain in Unger’s tube or port
admixing with the flush medium as it is administered to the patient for 5
minutes.
CONCLUSION OF LAW
Unger does not describe or suggest “delivering” an “admixed
product” of a contrast agent and flushing medium to a subject “over an
infusion period of 5-10 minutes” as recited in claim 1. We reverse the
rejection of claim 1 and dependent claims 3, 5-7, 11, 12, and 19 which
incorporate all the limitations of claim 1.

REVERSED

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