Ex Parte Wang

Board of Patent Appeals and Interferences

May 21, 2012

10651305 (B.P.A.I. May. 21, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CHIA-GEE WANG
__________

Appeal 2011-012258
Application 10/651,305
Technology Center 1600
__________

Before TONI R. SCHEINER, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of treatment using irradiation. The Examiner rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

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Statement of the Case
“The method of the invention utilizes the emission of Auger electrons
from elements, particularly heavy elements, that have been irradiated with x-
rays” (Spec. 3 ¶ 0009). The Specification teaches that these “electrons can
deliver concentrated dosages of ionizing radiation of more than 10
6
gray
(Gy) per activation to localized areas” (Spec. 3 ¶ 0009).
The Claims
Claims 1, 3, 5, 7, 12, 16-24, 26-36, 38, 40, 42, 47, 51-59, 61-65, 67,
69, 71, 76-88, 90, 92, 97, and 99 are on appeal. Claim 1 is representative
and reads as follows:
1. A method for preferential disruption of
malfunctioning cells in a living mammal, which
comprises:
(a) administering a compound which associates
with DNA in cells of said mammal, said compound
comprising a pre-selected element selected from the
group consisting of Pt, Ca, Ti, Br, I, Gd, Y and Ru; and
then
(b) irradiating a selected region, in which
malfunctioning cells having said compound associated
with DNA are located, with line emission x-rays from an
X-ray tube, said line emission X-rays being of an energy
selected to cause emission of Auger electrons from said
pre-selected element of said compound in a dose
effective to disrupt DNA proximate to the irradiated pre-
selected element, said dose for each activation of said X -
ray tube being at least about 10
6
Gy localized with a
distance of a few atomic diameters from the pre-selected
element, said selected region being a localized region
which predominantly contains the malfunctioning cells
so as to localize the effects of disrupting DNA to the
malfunctioning cells and to minimize the effect on
normal cells.
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The issue

The Examiner rejected claims 1, 3, 5, 7, 12, 16-24, 26-36, 38, 40, 42,
47, 51-59, 61-65, 67, 69, 71, 76-88, 90, 92, 97, and 99 under 35 U.S.C. §
103(a) as obvious over Mills
1
and Wang
2
(Ans. 5-7).
The Examiner finds that Mills teaches a method for inducing “tissue
necrosis in treating cancer, by administering a compound (e.g., cisplatin)
that binds to targeted tissue DNA, wherein said compound comprises an
atom (e.g., platinum) that is excitable with radiation in a distinct narrow
frequency band and energy level, causing an Auger electron cascade
resulting in radiolysis of DNA” (Ans. 5). The Examiner finds that Wang
“teaches the preferred line emission x-rays to be well known in the art” (id.
at 6).
The Examiner finds it obvious to “use the x-ray source taught by
Wang because of the increased convenience and logistics of using the
smaller and more easily transported x-ray tube as opposed to the synchrotron
taught by Mills” (id.).
Appellant contends that “the Auger cascade can be used to destroy the
cells without destroying other cells outside of the very small ionization
sphere” (App. Br. 5). Appellant contends that as “explained in the Wang
Declaration, the emission and absorption of gamma-rays in a solid under the
Mossbauer effect initiated by a nuclear decay is very different from the
Auger cascade and the Auger dose initiated by a controlled external photon
beam as claimed” (id.).

1
Mills, R., US 6,224,848 B1, issued May 1, 2001.
2
Wang, C., US 5,627,871, issued May 6, 1997.
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Appellant contends that in “Mills, the nuclei of administered isotopes
at the target tissue absorb gamma rays and undergo an internal conversion,
which is followed by an Auger electron cascade” (App. Br. 5). Appellant
contrasts that with the invention, contending that in “the claimed invention,
an Auger cascade commences when the atom, not the nucleus, has an inner
shell ionization caused by K-edge or L-edge absorption initiated by a
controlled external photon beam which leads to a number of low energy
Auger electrons in a cascade” (id.).
Appellant contends that “there could have been no reason or
motivation to modify Mills in the manner suggested by the Examiner as this
would improperly change the principle of operation of the reference.” (id. at
6). Appellant also contends that “Mills would not have provided even a
reasonable expectation of success with the claimed method since one of
ordinary skill in the art could not have expected that the use of external x-
rays generating the claimed dose of 10
6
Gy in situ could be made without
unacceptable damage to a patient” (id.).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion Mills and Wang render claim 1 obvious?
Findings of Fact
1. Mills teaches that for “therapeutic purposes, the energy is
converted to particle radiation by the isotope at the target tissue by internal
conversion followed by an Auger electron cascade which results in
radiolysis of DNA resulting in lethal double strand breaks in the DNA
molecules of the target tissue” (Mills, abstract).

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2. Mills teaches that:
A statistically significant effect was observed with
mrad levels of radiation. Previous studies indicate that at
least 500 rads of conventional X-rays or gamma rays is
necessary to register a similar effect. 500 rads is 5×10
5
times
the level of radiation used in these MIRAGE treatment
experiments. Furthermore, l mrad of radiation is far below
levels which are toxic and can be compared to 200 mrad
which is the yearly background dose.

(Mills, col. 12, ll. 45-52.)
3. Mills teaches “that the most potent killing effect in cells by
radiation is from secondary particles produced by internal conversion of
gamma ray energy followed by an Auger cascade which results in the
radiolysis of the cell's genetic material” (Mills, col. 12, ll. 57-60).
4. Mills teaches that “it is possible to effect this eradication
mechanism with nontoxic levels of radiation which are six orders of
magnitude less than that of conventional radiation therapy where the
Mossbauer effect was exploited for treatment” (Mills, col. 12, ll. 61-64).
5. Mills teaches that “one decay event of a radioactive atom such
as
125
I of internal conversion, followed by an Auger cascade which cause
radiolysis and double strand breakage is lethal to a cell” (Mills, col. 93, ll.
29-32).
6. Mills teaches that “the Auger electrons have energies up to a
few KeV with a relatively high linear energy transfer of 1 to 10 ev/nm. Since
such electrons dissipate their energy in materials of unit density within a
distance of the order of 10 to 100 nm they may efficiently damage molecules
in the nearness of the decay event” (Mills, col. 93, ll. 23-28).
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7. Mills teaches the use of cisplatin, a DNA binding compound
which contains platinum (Pt) (see Mills, col. 109, l. 8, Claim 1).
8. Mills teaches that
the apparatus includes a polarizing element, to polarize the
emission. Polarized gamma rays are obtained by three
methods: magnetized ferromagnetic sources, quadrapole
split sources, or filter techniques. In addition, the apparatus
possesses means to produce external magnetic fields and
ultrasonic beams to change the gamma ray energy and/or
polarization and propagation direction conditions to achieve
resonant absorption in the absorber atoms of the
pharmaceuticals to impart tissue selectivity

(Mills, col. 7, ll. 8-16).
9. Wang teaches that at “low energy operation, x-ray photons are
concentrated at 4.1 KV, which can excite Auger electrons of calcium in a
resist. At high energy operation, x-ray photons can excite transition metals
such as Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn” (Wang, col. 10, ll. 26-30).
Principles of Law
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993).
“[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).

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Analysis
The Examiner reasons that “the substitution of one monochromatic
energy source (which causes an Auger electron cascade in the target metal,
e.g., platinum in cisplatin) for another monochromatic energy source capable
of producing an Auger electron cascade” (Ans. 6) would have been obvious.
However, while the Examiner has established that both energy sources
induce an Auger cascade, the Examiner has not demonstrated that the X-ray
source of Wang is equivalent to the gamma rays of Mills in delivering
energy to a patient. That is, the Examiner has not provided evidence that an
X-ray source can deliver sufficient energy through the tissue of a living
mammal to induce an Auger cascade safely and without causing injury to the
patient.
We agree with Appellant that “Mills would not have provided even a
reasonable expectation of success with the claimed method since one of
ordinary skill in the art could not have expected that the use of external x-
rays generating the claimed dose of 10
6
Gy in situ could be made without
unacceptable damage to a patient” (App. Br. 6).
The Examiner finds that the “external x-ray source is not directly
irradiating the subject with 10
6
Gy as Appellant seems to be suggesting. The
10
6
Gy dose of the instant claims is that which is precipitated by the Auger
electrons of the target metal over a very short distance” (Ans. 10).
While we agree with the Examiner that the 10
6
Gy is the result of the
Auger cascade, not the X-ray irradiation, the Examiner has not established
that the dose of X-rays necessary to induce an Auger cascade in a DNA
binding compound within the living body of a patient would have reasonably
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been expected to be safe for patients. The essence of the rejection is based
on an improper obvious to try argument, since there is no evidence that the
combination had a reasonable expectation of success in treating cancer
without killing the mammal. Wang is not concerned with safety, since the
target in Wang is a microelectronic component, not a living mammal.
Therefore, in the absence of any suggestion of a reasonable expectation of
success, we see the invention as obvious to try at best, in view of the
combined teachings of Mills and Wang alone. That is not a proper standard
of obviousness. In re O’Farrell, 853 F.2d 894, 904 (Fed. Cir. 1988).
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
Mills and Wang render claim 1 obvious.
SUMMARY
In summary, we reverse the rejection of claims 1, 3, 5, 7, 12, 16-24,
26-36, 38, 40, 42, 47, 51-59, 61-65, 67, 69, 71, 76-88, 90, 92, 97, and 99
under 35 U.S.C. § 103(a) as obvious over Mills and Wang.

REVERSED

cdc