Ex Parte Abraham-Fuchs et al

Board of Patent Appeals and Interferences

Jun 9, 2009

10849328 (B.P.A.I. Jun. 9, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KLAUS ABRAHAM-FUCHS and MICHAEL MORITZ
__________

Appeal 2009-000920
Application 10/849,328
Technology Center 1600
__________

Decided:1 June 9, 2009
__________

Before DEMETRA J. MILLS, ERIC GRIMES, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

1 The two-month time period for filing an appeal or commencing a
civil action, as recited in 37 C.F.R. § 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 2009-000920
Application 10/849,328

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of determining energy dosages in patients. We have jurisdiction under 35
U.S.C. § 6(b). We reverse.
Statement of the Case
Background
“In particle beam therapy, a beam (or beams) of radiation in the form
of electrons, or photons, or more recently, protons, is delivered to a tumor or
other target tissue. The dosage of radiation delivered is intended to destroy
the tumorous cells or tissues” (Spec. 2, ll. 3-7). The Specification teaches
that “the dosage of energy that is planned for can often not be measured,
determined or monitored very accurately. Further, even if the planned
dosage of energy is delivered to a target tissue, it is not usually known until
after treatment whether the treatment succeeded in destroying the target
tissue” (Spec. 4, ll. 15-19).
The Claims
Claims 1-24 are on appeal. We will focus on independent claims 1
and 13, which are representative and read as follows:
1. A method for determining an actual dosage of energy
delivered from an energy delivery system to a target, said
target within a biological organism, said method comprising:
introducing a bio-molecular contrast agent (BMCA)
into said biological organism, said BMCA capable of at least
one of binding to said target and reacting with said target,
said BMCA also emitting signals, said signals capable of
being inactivated by interacting with said energy;
directing said energy delivery system to deliver
energy to said target after said BMCA has bound or reacted
to said target; and
2
Appeal 2009-000920
Application 10/849,328

during delivery, determining said actual dosage based
on BMCA signals originating from said target.

13. A method for determining destruction of a target by
delivery of energy from an energy delivery system, said
target within a biological organism, said method comprising:
introducing a bio-molecular contrast agent (BMCA)
into said biological organism, said BMCA capable of at least
one of binding to said target and reacting with said target,
said BMCA also emitting signals, said signals capable of
being inactivated by interacting with said energy;
directing said energy delivery system to deliver
energy to said target after said BMCA has bound or reacted
to said target; and
during delivery, determining a level of destruction of
DNA in said target based on BMCA signals originating from
said target.

The prior art
The Examiner relies on the following prior art references to show
unpatentability:
Ikegami et al. US 5,856,673 Jan. 5, 1999
Weissleder et al. US 6,083,486 Jul. 4, 2000
Hochman US 6,319,682 B1 Nov. 20, 2001
Green US 6,843,980 B1 Jan. 18, 2005
Lauffer WO 99/17809 Apr. 15, 1999

The issues2
A. The Examiner rejected claims 1-8, 11-20, 23, and 24 under 35 U.S.C.
§ 112, first paragraph, written description (Ans. 3).

2 Appellants did not identify the provisional double patenting
rejections as grounds of rejection to be reviewed on appeal (App.
Br. 3).
3
Appeal 2009-000920
Application 10/849,328

B. The Examiner rejected claims 1-24 under 35 U.S.C. § 112, first
paragraph, enablement (Ans. 4-6).
C. The Examiner rejected claims 1-12 under 35 U.S.C. § 103(a) as being
obvious over Lauffer, Ikegami and Hochman (Ans. 6-9).
D. The Examiner rejected claims 13-24 under 35 U.S.C. § 103(a) as
being obvious over Lauffer, Hochman and Green (Ans. 9-10).
A. 35 U.S.C. § 112 first paragraph, written description
The Examiner rejected claims 1-8, 11-20, 23, and 24 under 35 U.S.C.
§ 112, first paragraph, written description (Ans. 3).
The Examiner finds that the “claimed invention relates to the method
for determining an actual dosage of energy delivered from an energy
delivery system to a target, which encompasses the introduction of any bio-
molecular contrast agent into any target but there are no bio-molecular
contrast agents or targets disclosed in the specification” (Ans. 3).
Appellants contend that “the specification complies with the written
description requirement even if no bio-molecular contrast agents or targets
are disclosed in the specification for carrying out the invention of the instant
claim” (App. Br. 4). Appellants contend that the “present specification and
figures are replete with descriptions in which a BMCA binds to a target or
reacts with a target, and emits signals capable of being inactivated by
interacting with energy from an energy delivery system” (App. Br. 4).
In view of these conflicting positions, we frame the written
description issue before us as follows:
Did the Examiner err in finding that the Specification did not
demonstrate possession of any bio-molecular contrast agents or targets as
required by claims 1 and 13?
4
Appeal 2009-000920
Application 10/849,328

Findings of Fact (FF)
1. The Specification teaches that
“BMCA” as the term is used in describing this invention, are
at least partially organic contrast agents which have the
following properties: 1) they bind to target tissue, cells, and
organs, and/or (2) react with metabolic products of the target
tissue, cells, and organs by means of highly specific
biochemical reactions (such as body- anti-body
mechanisms).

(Spec. 6, ll. 4-10.)
2. The Specification teaches that “fluorescent BMCAs, such as the
ones described in U.S. Patent Number 6,083,486, can be used in conjunction
with a medical optical imager” (Spec. 6, ll. 19-21).
3. The Specification teaches that “[s]everal different targeted
contrast agents which bind to particular tissue and then exhibit signal
changes based upon state changes in tissues (which are then imaged) are
disclosed in international patent application WO 99/17809, entitled
‘Contrast-Enhanced Diagnostic Imaging Method for Monitoring
Interventional Therapies’” (Spec. 4, ll. 9-14).
4. Lauffer (WO 99/17809 disclosed in the Specification) teaches
contrast agents with two domains, where the “first domain of the contrast
agents . . . is an IEM [image enhancing moiety] which can be any chemical
or substance used to provide the signal or contrast in imaging” (Lauffer 13,
ll. 12-14).
5. Lauffer teaches the specific structure for eight different image
enhancing moieties (Lauffer 42).
6. Lauffer teaches that the “second domain of the contrasts agents
. . . is a state-dependent tissue binding moiety (SDTBM) which provides the
5
Appeal 2009-000920
Application 10/849,328

targeting functionality to the agent . . . the specific structure of the SDTBM
will depend on the specific tissue or tissue component to be bound” (Lauffer
18, ll. 9-15).
Principles of Law
In order to satisfy the written description requirement, “the applicant
must … convey with reasonable clarity to those skilled in the art that, as of
the filing date sought, he or she was in possession of the invention.” Vas-
Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991). Thus,
“[t]he possession test requires assessment from the viewpoint of one of skill
in the art.” Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1320
(Fed. Cir. 2003).
[W]e hold, in accordance with our prior case law, that (1)
examples are not necessary to support the adequacy of a
written description (2) the written description standard may
be met (as it is here) even where actual reduction to practice
of an invention is absent; and (3) there is no per se rule that
an adequate written description of an invention that involves
a biological macromolecule must contain a recitation of
known structure.

Falko-Gunter Falkner v. Inglis, 448 F.3d 1357, 1366 (Fed. Cir. 2006). See,
e.g., LizardTech, Inc. v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1345
(Fed. Cir. 2005) (“it is unnecessary to spell out every detail of the invention
in the specification; only enough must be included to convince a person of
skill in the art that the inventor possessed the invention.”)
Analysis
We agree with Appellants that the Specification demonstrates
possession of the claimed invention. The claims are not directed towards
novel contrast agents, but rather to novel methods of using existing contrast
6
Appeal 2009-000920
Application 10/849,328

agents (see Claims 1, 13). While the Examiner is correct that the
Specification does not list specific contrast agents, the Specification defines
bio-molecular contrast agents (FF 1) and demonstrates that such agents are
known in the art (FF 2-6). See Hybritech Inc. v. Monoclonal Antibodies,
Inc., 802 F.2d 1367, 1384 (Fed. Cir. 1986) (“a patent need not teach, and
preferably omits, what is well known in the art.”) This is sufficient to place
the inventor in possession of the instantly claimed invention, which is drawn
to methods where any prior art known bio-molecular contrast agent can be
used to determine the dosage of energy delivered or the level of DNA
destruction in a target, and not to novel contrast agents (see Claims 1, 13).
Conclusion of Law
The Examiner erred in finding that the Specification did not
demonstrate possession of any bio-molecular contrast agents or targets as
required by claims 1 and 13.
We reverse the rejection of claims 1-8, 11-20, 23, and 24 under 35
U.S.C. § 112, first paragraph, written description.
B. 35 U.S.C. § 112 first paragraph, enablement
The Examiner rejected claims 1-24 under 35 U.S.C. § 112, first
paragraph, enablement (Ans. 4-6).
The Examiner finds that “the specification, while being enabling for
bio-molecular contrast agent[s] of the type described in US patent 6,083,486
as incorporated by reference, does not reasonably provide enablement for all
bio-molecular contrast agent[s]” (Ans. 4).
Appellants contend that “one in the art would have no difficulty
selected [sic] a BMCA as claimed to utilize [in] the claimed method” (App.
Br. 5). Appellants contend that “the specification is not required to enable
7
Appeal 2009-000920
Application 10/849,328

the use of all bio-molecular contrast agents since the claims recite only
BMCAs capable of binding to a target or reacting with a target, and emitting
signals capable of being inactivated by interacting with energy from an
energy delivery system” (App. Br. 5).
In view of these conflicting positions, we frame the enablement issue
before us as follows:
Did the Examiner err in finding that it would have required undue
experimentation to determine an actual dosage of energy using bio-
molecular contrast agents?
Findings of Fact
Breadth of the Claims
7. Claim 1 is drawn to a “BMCA capable of at least one of
binding to said target and reacting with said target, said BMCA also emitting
signals, said signals capable of being inactivated by interacting with said
energy” (see Claim 1).
8. The Examiner finds that the “claims are very broad and
inclusive of ‘introducing a bio-molecular contrast agent into a biological
organism’, which includes any bio-molecular contrast agent into any
biological organism” (Ans. 5).
Amount of Direction or Guidance Presented
9. The Examiner finds that “the specification provides no direction
for ascertaining, a priori, which bio-molecular contrast agent is to be used to
carry out the invention” (Ans. 5-6).
10. The Specification teaches that “fluorescent BMCAs, such as the
ones described in U.S. Patent Number 6,083,486, can be used in
8
Appeal 2009-000920
Application 10/849,328

conjunction with a medical optical imager, like an optical tomograph or a
diaphanoscope” (Spec. 6, ll. 19-22).
11. The Specification teaches that
BMCAs can also be designed or selected such that
their signal-giving property diminishes when the BMCA
interacts with the particle beam. The BMCA can thus be
"inactivated" (with respect to its signal-giving property)
through irradiation with a particle beam of enough energy.
For instance, a fluorescent contrast agent may be inactivated
by destroying the fluorescence property of the BMCA which
would involve breaking of the functional covalent C-C
and/or C-H bindings of the BMCA through irradiation.

(Spec. 7, ll. 6-14.)
State of the Art and Unpredictability of the Art
12. The Examiner finds “unpredictability present in this art with
regard[] to site specific targeting contrast agents” (Ans. 6).
Principles of Law
“In order to satisfy the enablement requirement of section 112, an
applicant must describe the manner of making and using the invention ‘in
such full, clear, concise, and exact terms as to enable any person skilled in
the art … to make and use the same ….’ 35 U.S.C. § 112, para. 1.”
Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1322 (Fed. Cir.
2005).
Factors to be considered in determining whether a
disclosure would require undue experimentation … include
(1) the quantity of experimentation necessary, (2) the
amount of direction or guidance presented, (3) the presence
or absence of working examples, (4) the nature of the
invention, (5) the state of the prior art, (6) the relative skill
of those in the art, (7) the predictability or unpredictability
of the art, and (8) the breadth of the claims.
9
Appeal 2009-000920
Application 10/849,328

In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
The Examiner has the initial burden to establish a reasonable basis to
question the enablement provided for the claimed invention. See In re
Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993) (Examiner must provide a
reasonable explanation as to why the scope of protection provided by a
claim is not adequately enabled by the disclosure).
Analysis
The Specification provides some teachings on bio-molecular contrast
agents which can be used in the claimed methods, including citation of a
prior patent which discloses specific chemical structures (FF 10-11).
The Examiner, while concluding that there is unpredictability, cites no
art or evidence to suggest that selection of bio-molecular contrast agents
other than those disclosed in the cited prior art patent would be
unpredictable (FF 12).
Balancing the Wands factors, we agree with Appellants that undue
experimentation would not have been required to make and use the claimed
invention. To the extent that the Examiner argues the “how to use” prong,
the prior art clearly teaches a variety of bio-molecular contrast agents as
evidenced both in the Specification and in the prior art cited for obviousness.
There is no evidence to suggest that some bio-molecular contrast
agents would fail to function and there is no reasonable reason to doubt that
radiation doses could be measured using the bio-molecular contrast agents as
required by the claims (FF 7-11).
The Examiner's position that the Specification cannot teach how to
use the claimed method unless it teaches solutions to all possible species and
10
Appeal 2009-000920
Application 10/849,328

all possible bio-molecular contrast agents is contrary to controlling case law.
See, e.g., In re Brana, 51 F.3d 1560, 1568 (Fed. Cir. 1995).
Conclusion of Law
The Examiner erred in finding that it would have required undue
experimentation to determine an actual dosage of energy using bio-
molecular contrast agents.
We reverse the rejection of claims 1-24 under 35 U.S.C. § 112, first
paragraph, enablement.
C. 35 U.S.C. § 103(a) over Lauffer, Ikegami and Hochman
The Examiner rejected claims 1-12 under 35 U.S.C. § 103(a) as being
obvious over Lauffer, Ikegami and Hochman (Ans. 6-9).
The Examiner finds that it would have been obvious to “use the
method of measuring depth dose of energy as disclosed by Ikegami . . . to
determine the dose of energy delivered from a[n] energy delivery system
since the Ikegami et al. model is a based on a representation of actual human
tissue” (Ans. 9). The Examiner finds that Lauffer “discloses monitoring
whether the interventional therapy is complete which would entail watching
the applied dosage” (Ans. 9). The Examiner finds that “Hochman . . .
discloses that a reduction in physiological activity generally corresponds to a
decrease of emr absorption capacity of the tissue . . . and at this time it
would also be obvious to discontinue the delivery of energy to a subject”
(Ans. 9).
Appellants contend that the prior art fails “to disclose or suggest
determining an actual dosage during delivery based on BMCA signals
originating from the target. The combination also fails to disclose or suggest
BMCA signals capable of being inactivated by interaction of the BMCA
11
Appeal 2009-000920
Application 10/849,328

with energy delivered to a target that has bonded or reacted with the BMCA”
(App. Br. 6).
In view of these conflicting positions, we frame the obviousness issue
before us as follows:
Did the Examiner err in finding that the combination of Lauffer,
Ikegami and Hochman suggests determining “an actual dosage based on
BMCA signals originating from” a target as required by claim 1?
Findings of Fact
13. Lauffer teaches “methods of MRI and optical imaging which
use contrast agents that target a specific tissue or tissue component and
permit the monitoring of state changes in the targeted tissue . . . that occur
during or after interventional therapy” (Lauffer 1, ll. 7-12).
14. Lauffer teaches that “[t]o obtain the maximum benefit from
such interventional methods, and to minimize side effects (e.g., damage to
adjacent tissues), it is essential to monitor, in vivo, the efficacy of the
therapy” (Lauffer 4, ll. 6-9).
15. Lauffer teaches contrast agents with “state-dependent binding
to a targeted tissue or tissue component. Such binding leads to a detectable
change in the signal characteristics of the contrast agent and thus, permits
the determination of state changes within a targeted tissue” (Lauffer 9, ll. 15-
19). Lauffer notes that “[f]ollowing administration of the appropriate dosage
of the contrast agent, the patient is then subjected to either MRI or optical
imaging (ultraviolet light, visible light or infrared light imaging)” (Lauffer
48, ll. 31-34).
12
Appeal 2009-000920
Application 10/849,328

16. Ikegami teaches “a depth dose measuring apparatus capable of
measuring dose distribution in depth of human body” (Ikegami, col. 2, ll. 9-
11).
17. Ikegami teaches “a depth dose measuring apparatus, in which a
fluorescent substance block bundling scintillation fibers having radiation
absorption characteristic close to that of tissue is disposed orthogonally to
the incident direction of radiation . . . the absorption dose distribution can be
measured simultaneously by one irradiation” (Ikegami, col. 2, ll. 15-25).
18. Ikegami teaches the importance of “determining the parameter
of irradiation beam suited to the shape and dimensions of the cancer tissue
subject to irradiation” (Ikegami, col. 1, ll. 63-65).
19. Hochman teaches that “it may, however, be useful to administer
contrast enhancing agents that amplify differences in an optical property
being detected as a function of physiological activity prior to acquiring
subsequent data and generating a comparison” (Hochman, col. 10, ll. 19-23).
20. Hochman teaches that “a reduction in physiological activity
generally corresponds to a decrease of emr absorption capacity of the tissue”
(Hochman, col. 17, ll. 1-3).
21. Hochman teaches that the method involves “optical, or
spectroscopic, detection techniques to assess the physiological state of
biological materials” (Hochman, col. 4, ll. 13-15)
Principles of Law
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
13
Appeal 2009-000920
Application 10/849,328

nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
The Supreme Court has emphasized that “the [obviousness] analysis need
not seek out precise teachings directed to the specific subject matter of the
challenged claim, for a court can take account of the inferences and creative
steps that a person of ordinary skill in the art would employ.” KSR Int'l Co.
v. Teleflex Inc., 550 U.S. 398, 418 (2007).
KSR holds that an invention “composed of several elements is not
proved obvious merely by demonstrating that each of its elements was,
independently, known in the prior art.” Id. There must be “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.” Id.
Analysis
Lauffer teaches methods of monitoring state changes in tissue using
bio-molecular contrast agents (FF 13-15) and Hochman also teaches using
contrast agents to analyze tissue effects of interventions (FF 19-20).
Ikegami teaches a depth dose measuring device (FF 16-18).
However, the contrast agents of Lauffer are either optical or MRI
imaging agents, as Lauffer notes that “[f]ollowing administration of the
appropriate dosage of the contrast agent, the patient is then subjected to
either MRI or optical imaging (ultraviolet light, visible light or infrared light
imaging)” (Lauffer 48, ll. 31-34; FF 15). Hochman teaches that the method
involves “optical, or spectroscopic, detection techniques to assess the
physiological state of biological materials” (Hochman, col. 4, ll. 13-15; FF
21).
Neither Lauffer nor Hochman teach that the contrast agents are
sensitive to radiation such as gamma rays or high-energy X-rays, as
14
Appeal 2009-000920
Application 10/849,328

measured in Ikegami (Ikegami, col. 1, ll. 4-15). Consequently, the Examiner
has not explained why the person of ordinary skill in the art would have
substituted these agents into Ikegami’s radiation measuring device and
method.
We are persuaded by Appellants’ argument that the prior art does not
“disclose or suggest BMCA signals capable of being inactivated by
interaction of the BMCA with energy delivered to a target that has bonded or
reacted with the BMCA” (App. Br. 6). The prior art combination relies
upon Ikegami, who measures depth dosage with X-ray radiation and the
Examiner has not identified where the cited prior art of Lauffer and
Hochman teach or suggest contrast agents with signals which would be
inactivated by the X-ray radiation of Ikegami.
Conclusion of Law
The Examiner erred in finding that the combination of Lauffer,
Ikegami and Hochman suggest determining an “actual dosage based on
BMCA signals originating from” a target as required by claim 1.
We reverse the rejection of claims 1-12 under 35 U.S.C. § 103(a) as
being obvious over Lauffer, Ikegami and Hochman.
D. 35 U.S.C. § 103(a) over Lauffer, Hochman and Green
The Examiner rejected claims 13-24 under 35 U.S.C. § 103(a) as
being obvious over Lauffer, Hochman and Green (Ans. 9-10).
The Examiner finds that it would have been obvious “to monitor
whether the interventional therapy is complete, such as by monitoring state
changes of target tissues as is disclosed by Lauffer . . . by visualizing cell
death by optical imagin[g] as is disclosed by Green” (Ans. 10).
15
Appeal 2009-000920
Application 10/849,328

Appellants contend that the art does not teach “determining a level of
destruction of DNA in a target based on BMCA signals originating from the
target during delivery of energy to the target” (App. Br. 7).
In view of these conflicting positions, we frame the obviousness issue
before us as follows:
Did the Examiner err in finding that the combination of Lauffer,
Hochman and Green suggests determining “a level of destruction of DNA in
said target based on BMCA signals originating from said target” as required
by claim 13?
Findings of Fact
22. Green teaches that “the combination of an annexin with an
optically active molecule, such as a fluorescent dye, allows for the efficient
and effective detection of cells undergoing cell death by optical imaging”
(Green, col. 6, ll. 1-4).
Analysis
Lauffer teaches monitoring for tissue changes, but the Examiner does
not identify any teaching in Lauffer which suggests measurement of levels
of destruction of DNA. Similarly, the Examiner identifies no teaching in
either Hochman or Green in which the levels of destruction of DNA in a
target are measured. At best, Green teaches an association with cell death
and changes in contrast dyes, but Green does not teach that the levels of
DNA destruction are associated with changes in fluorescent dyes (see FF
22).
The Examiner concludes that “it would be obvious to
measure/monitor the level of destruction of DNA of a cell via fluorescence
and discontinue therapy based on the physiological state of the cells in view
16
Appeal 2009-000920
Application 10/849,328

of the combined disclosures of Lauffer et al. and Hochman” (Ans. 17).
However, the Examiner provides no evidence or teaching that levels of DNA
destruction are measured or how levels of DNA destruction relate to
apoptosis in the context of a claim drawn to “determining a level of
destruction of DNA in said target” as required by claim 13.
We appreciate that Green teaches that the modes of cell death include
apoptosis and necrosis (Green, col. 6, l. 14) and that apoptosis is the process
of programmed cell death which includes fragmentation of the DNA in the
cell. The Examiner has not provided sufficient evidence for a prima facie
case that the prior art of Green, Lauffer and Hochman teach correlating
destruction of a target with levels of destruction of DNA as required by
claim 13.
Conclusion of Law
The Examiner erred in finding that the combination of Lauffer,
Hochman and Green suggest determining “a level of destruction of DNA in
said target based on BMCA signals originating from said target” as required
by claim 13.
We reverse the rejection of claims 13-24 under 35 U.S.C. § 103(a) as
being obvious over Lauffer, Hochman and Green.
SUMMARY
In summary, we reverse the rejection of claims 1-8, 11-20, 23, and 24
under 35 U.S.C. § 112, first paragraph, written description.
We reverse the rejection of claims 1- 24 under 35 U.S.C. § 112, first
paragraph, enablement.
We reverse the rejection of claims 1-12 under 35 U.S.C. § 103(a) as
being obvious over Lauffer, Ikegami and Hochman.
17
Appeal 2009-000920
Application 10/849,328

We reverse the rejection of claims 13-24 under 35 U.S.C. § 103(a) as
being obvious over Lauffer, Hochman and Green.

REVERSED

cdc

BRINKS HOFER GILSON & LIONE
P.O. BOX 10395
CHICAGO IL 60610
18