Ex Parte Jiang et al

Patent Trial and Appeal Board

Dec 12, 2017

12532344 (P.T.A.B. Dec. 12, 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
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/532,344 03/15/2010 Yun Jiang ISIS-13470/US-2/PCT 6915
58057 7590 12/14/2017
Pasimir Tones; P
EXAMINER
2275 Deming Way, Suite 310
Madison, WI 53562
BERTAGNA, ANGELA MARIE
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
12/14/2017 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):
docketing @ c asimirj ones .com
pto.correspondence@casimirjones.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YUN JIANG, LENDELL L. CUMMINS,
and STEVEN A. HOFSTADLER1
Appeal 2016-008372
Application 12/532,344
Technology Center 1600
Before ERIC B. GRIMES, RYAN A. FLAX, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for purifying nucleic acids, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
“The techniques of molecular biology often require the purification of
nucleic acids away from other compounds.” (Spec. 13.)
Use of coated magnetic beads to bind nucleic acids in a reaction
mixture offers several advantages. . . . Using this technique,
1 Appellants identify the Real Party in Interest as Ibis Biosciences, Inc.
(Appeal Br. 3.)
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Application 12/532,344
samples are lysed and incubated with a binding buffer. After
addition of the magnetic beads, nucleic acids released from the
samples are bound to the bead surface. Unbound contaminants
are removed in subsequent washing steps. Thereafter, the
purified nucleic acid is eluted from the beads.
{Id. 14.)
The Specification states that
[sjurprisingly, in experiments conducted in the course of
development of embodiments of the present invention, it was
found that compared to other additives to the binding buffer (for
example, polyethylene glycol or PEG), the addition of
polyoxyethylene sorbitan monolaureate (TWEEN 20) resulted in
greater nucleic [acid] recovery, and a faster purification
procedure.
{Id. 178.) The Specification also states that “the addition of at least one
alcohol and at least one salt to a binding buffer further comprising a
polyoxyethylene sorbitan further improves the efficiency and yield of the
purification.” {Id. 179.)
Claims 1—10 and 24—31 are on appeal. Claim 1 is illustrative and
reads as follows:
1. A method for nucleic acid purification,
comprising:
a) combining a binding buffer comprising at at least 20%
and less than 30% polyoxyethylene sorbitan monolaurate, at
least 10% ethanol and 1.0 to 2.5 M NaCl with at least one
paramagnetic particle to generate a suspension;
b) combining at least one sample comprising at least one
nucleic acid with said suspension, wherein said paramagnetic
particle reversibly captures said nucleic acid to generate a
combination comprising said paramagnetic particle with said
captured nucleic acid; and
c) separating said paramagnetic particle with said captured
nucleic acid from one or more other components of the
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combination using a magnetic separator, thereby purifying said
nucleic acid.
DISCUSSION
The Examiner has rejected all of the claims on appeal under 35 U.S.C.
§ 103(a) as obvious based on Hawkins ’628,2 Hawkins NAR,3 Templer,4
Deggerdal,5 and Gundling.6 (Ans. 3.) The Examiner finds that Hawkins
’628 teaches a nucleic acid purification method using coated magnetic
particles and a binding buffer comprising 0.5—5 M NaCl. {Id. at 3 4.) The
Examiner also finds that the method of Hawkins ’628 includes steps (b) and
(c) of claim 1. {Id. at 3.) The Examiner finds that Hawkins NAR provides
evidence that the particles used in the method of Hawkins ’628 are
paramagnetic particles. {Id. at 4.)
The Examiner finds that Hawkins ’628 does not teach a binding buffer
comprising polyoxyethylene sorbitan monolaurate and ethanol, and does not
teach combining paramagnetic particles with the binding buffer before
combining that mixture with a sample. {Id. at 4.) The Examiner finds that
Templer discloses a magnetic particle-based nucleic acid purification
method in which the binding buffer comprises a salt and an alcohol in an
amount of at least 10%. (Id. at 4—5.)
2 Hawkins, US 5,705,628, issued Jan. 6, 1998.
3 Hawkins et al., DNA purification and isolation using a solid-phase, 22(21)
Nucleic Acids Research 4543^44 (1994).
4 Templer, US 2007/0026435 Al, published Feb. 1, 2007.
5 Deggerdal et al., US 2006/0058519 Al, published Mar. 16, 2006
6 Gundling, US 2002/0068821 Al, published June 6, 2002.
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Application 12/532,344
The Examiner finds that Deggerdal describes a magnetic particle-
based nucleic acid purification method in which the binding buffer
comprises a detergent, and optionally a salt, although it does not specifically
teach polyoxyethylene sorbitan monolaurate as the detergent. {Id. at 5—6.)
The Examiner finds, however, that Gundling shows that “polyoxyethylene
sorbitan monolaurate was known in the art at the time of the invention to be
a non-ionic detergent suitable for inclusion in buffers for binding nucleic
acids to magnetic particles.” {Id. at 6.)
The Examiner concludes that it would have been obvious to “include
polyoxyethylene sorbitan monolaurate in the binding buffer used in the
method of Hawkins [’628]” because “Deggerdal taught that the presence of a
detergent (e.g., a non-ionic detergent) during a step of binding nucleic acids
in a sample to particles, such as paramagnetic particles, reduces nonspecific
co-adsorption of protein contaminants.” {Id.) The Examiner also concludes
that it would have been obvious to include an alcohol in the binding buffer
of Hawkins ’628 because “Templer . . . indicate[s] that ethanol at a
concentration within the claimed ranges was known in the art to promote
binding of nucleic acids to paramagnetic particles.” {Id. at 7.) Finally, the
Examiner concludes that mixing paramagnetic particles with the binding
buffer before adding it to a sample would have been obvious because
Deggerdal “indicate [s] that reagents used in a step of binding nucleic acids
in a sample to a solid support may be added to the sample together or
separately.” {Id. at 8.)
We agree with the Examiner that the cited references support a prima
facie case of obviousness. Hawkins ’628 discloses “a method of separating
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DNA from a solution” comprising “a first step of reversibly binding DNA
non-specifically to a solid surface, such as magnetic microparticles whose
surfaces are coated with functional groups.” (Hawkins ’628 2:34—38.) “In
one embodiment, the functional group is a carboxylic acid.” {Id. at 3:34—
35.)
[T]he magnetic microparticles are combined with a solution of
DNA, after which the salt concentration and the polyethylene
glycol concentration of the resulting combination are adjusted
... to result in a final concentration of from about 0.5M to about
5.0M salt and from about 7% to about 13% polyethylene glycol.
{Id. 2:39-48.) “Subsequently, the magnetic microparticles in the resulting
combination are separated from the supernatant.” {Id. at 2:50-51.) Hawkins
NAR provides evidence that carboxyl-coated magnetic particles are
superparamagnetic. (Hawkins NAR 4543, left col.)
Templer also discloses a method that “comprises a step of reversibly
binding nucleic acids to paramagnetic particles whose surfaces are coated
with functional groups comprising hydroxyls.” (Templer 116.) “[T]he
paramagnetic particles are combined with a solution of nucleic acid, after
which the salt concentration and/or the alcohol concentration of the resulting
combination are adjusted to binding concentrations suitable for binding
nucleic acids to the surface of the paramagnetic particles.” {Id.)
Templer states that
[t]he binding buffer comprises at least one of a suitable salt and
a suitable alcohol, which is present at concentration suitable for
binding nucleic acids to the surface of the paramagnetic particles.
It is preferred that the salt is sodium chloride at a concentration
from 0.1 to 0.5 M and the alcohol is ethanol at a concentration of
50 to 100 vol. %.
{Id. 136.)
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Deggerdal discloses that a “nucleic acid may be isolated from a
sample in a form suitable for amplification or other downstream processes,
by a simple and easy to perform procedure which involves treating the
sample with detergent and allowing the nucleic acid to bind to a solid
support.” (Deggerdal 113.) The solid support is preferably magnetic beads.
{Id. 143.) Deggerdal states that “[t]he detergent functions in the method to
lyse the nucleic acid containing material. . . . The detergent is also believed
to help to disrupt the binding of proteins, eg. DNA-binding proteins, to the
nucleic acid and to reduce the problem of contaminants in the sample
sticking to the solid support.” {Id. 137.) Deggerdal states that “[t]he
detergent may be any detergent, and a vast range are known and described in
the literature. Thus, the detergent may be ionic, including anionic and
cationic, non-ionic or zwitterionic.” {Id. 121.)
Gundling discloses “a method for separating nucleic acid from a test
sample comprising the steps of contacting a test sample with a metal oxide
support material. . . separating the complexes from the test sample; and
eluting the nucleic acid from the metal oxide support material.” (Gundling
1 6.) Gundling states that “[t]he binding buffer generally will comprise a
chaotropic agent and a detergent.” {Id.) Gundling discloses that “[t]he
binding buffers may also contain detergents well known to those skilled in
the art such as non-ionic detergents, ionic detergents, zwitterionic
detergents, at a total concentration of between 1% and 25% and preferably
between 5% and 20%.” {Id. 113.) Gundling states that the binding buffer
can also include an alcohol, including ethanol, at concentrations of 15% or
less. {Id. 115.) In a working example, Gundling describes isolating HIV
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RNA from plasma samples, in which “[t]he metal oxide procedure was
performed by mixing 1 ml of test plasma sample with 6 ml of binding buffer
(5M guanidinium isothiocyanate, 10% Tween-20, 16 mM cetyltrimethyl-
ammonium bromide, 100 mM dithiothreitol, 100 mM Na acetate, pH 4.1)
and 5 mg of Fe2C>3 particles.” (Id. 136.)
Based on the teachings of Hawkins ’628, Hawkins NAR, Templer,
Deggerdal, and Gundling, we agree with the Examiner that it would have
been obvious to a person of ordinary skill in the art to include at least 10%
ethanol and 20-30% Tween 20 (polyoxyethylene sorbitan monolaurate; see
Spec. 178) in the binding buffer of Hawkins ’628, because Templer teaches
that a binding buffer that contains more than 10% ethanol is “suitable for
binding nucleic acids to the surface of the paramagnetic particles” (Templer
136), Deggerdal teaches that including a detergent in a binding buffer
“reduce[s] the problem of contaminants in the sample sticking to the solid
support” (Deggerdal 137), and Gundling teaches a binding buffer that
includes 1—25%, preferably 5—20% of detergent, including Tween 20. Thus,
all of the components of the binding buffer recited in claim 1 were known
for use in the same type of nucleic acid purification process, and it would
have been obvious to include them with a reasonable expectation that the
resulting buffer would also be suitable in such processes.
Appellants argue that “Deggerdal’s methods expressly direct the
skilled artisan away from the Office’s combinations, and away from the
binding buffers and methods of the presently claimed invention.”
(Appeal Br. 11.) Appellants point to Deggerdal’s discussion of known
methods for isolating nucleic acids, and its statement that alcohols and
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Application 12/532,344
chaotropes “tend to interfere with many enzymic reactions and other
downstream processing applications.” {Id., quoting Deggerdal 14.)
Appellants also argue that Deggerdal describes its method as being carried
out in the absence of any chaotropic agent, and argue that the reference
therefore directs the skilled worker away from ethanol and polyethylene
glycol (PEG) because both of these agents are chaotropic. {Id. at 11—12.)
These arguments are unpersuasive. Regarding Deggerdal’s
description of prior art techniques as having the disadvantage that alcohols
or chaotropes tend to interfere with enzymatic reactions, Deggerdal also
states that the prior art “describes a method whereby nucleic acid is trapped
on the surface of a solid phase by precipitation. Generally speaking,
alcohols and salts are used as precipitants.” (Deggerdal 111.) Deggerdal
also states that “such methods speed up the nucleic acid separation process.”
{Id. 112.)
Deggerdal also states that “there are disadvantages associated with the
use of alcohols, chaotropes, and similar agents.” {Id.) Specifically,
chaotropes can result in viscous solutions, and alcohols can interfere with
subsequent enzymatic reactions. {Id.) Nonetheless, the reference provides a
reason to use alcohols or chaotropes; specifically, to speed up the separation
process. Therefore, a skilled artisan interested in speeding up the separation
process would have considered it obvious to include an alcohol or chaotrope
in the binding buffer. See Medichem S.A. v. Rolabo S.L., 437 F.3d 1157,
1165 (Fed. Cir. 2006) (“‘The fact that the motivating benefit comes at the
expense of another benefit, however, should not nullity its use as a basis to
modify the disclosure of one reference with the teachings of another.
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Application 12/532,344
Instead, the benefits, both lost and gained, should be weighed against one
another.’” (quoting WinnerInt7Royalty Corp. v. Wang, 202 F.3d 1340,
1349 n.8 (Fed. Cir. 2000))).
In any event, Hawkins ’628 discloses a binding buffer that includes
PEG and Templer discloses a binding buffer that includes ethanol. Those
references provide evidence that both PEG and ethanol are appropriate
components of a binding buffer for separating nucleic acids using magnetic
particles. The Examiner relies on Deggerdal only for its suggestion to also
include a detergent in order to reduce the problem of protein contaminants
binding to a solid support. (See Ans. 9.) Cf. Orthopedic Equip. Co. v.
United States, 702 F.2d 1005, 1013 (Fed. Cir. 1983) (“Claims maybe
obvious in view of a combination of references, even if the features of one
reference cannot be substituted physically into the structure of the other
reference.”).
Appellants also argue that Gundling teaches a binding buffer that
comprises a chaotropic agent and therefore is incompatible with the other
cited references. (Appeal Br. 17.) Appellants argue that “the incompatible
teachings of Degerdal [sic] and Gundling stand as firm evidence that artisans
of at least ordinary, if not extraordinary, skill would not have been motivated
to make the Office’s speculative combination of references.” {Id. at 18.)
However, as the Examiner pointed out (Ans. 14), the rejection relies
on Gundling only as evidence that Tween 20 is useful in nucleic acid
purification. That is, Gundling provides a reason to use Tween 20 as the
detergent suggested by Deggerdal, because Gundling shows that Tween 20
was known to be useful in similar purification processes. The rejection is
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not based on physically combining the binding buffers that are disclosed in
the different references.
In the Reply Brief, Appellants argue that
[t]he proper test of obviousness is whether one of skill in the art
would have been motivated to combine the elements to yield
the claimed combination i.e., binding buffers without PEG. . ..
Moreover, a proper test of obviousness is not supported by the
Office’s picking and choosing of terms and passages of a
reference (i.e., designation of “teachings relied upon”) to the
neglect of the reference as a whole.
(Reply Br. 3.)
These arguments are also unpersuasive. First, claim 1 recites a
binding buffer “comprising” the recited components, and is therefore open to
including other components (including PEG) in the binding buffer. Second,
considering the teachings of the references as a whole does not require
bodily incorporation of one composition into another. Rather, it simply
requires the Examiner to have a full understanding of the cited references
and whether they include a potential teaching away from the claimed
invention. See, e.g., In re Enhanced Sec. Research, LLC, 739 F.3d 1347,
1356 (Fed. Cir. 2014) (holding that not having a complete document did not
render the PTO’s obviousness determination improper where “[njothing in
the table of contents or the available chapter five pages suggests that the
missing content contradicts the available portions of chapter five on which
the PTO relied or other parts of the [reference].”). The Examiner here
considered the references as a whole, and we find no teaching away from the
claimed combination of components in a binding buffer.
Appellants argue that “Templer is aware of Hawkins’ methods, and
provides evidence of their inferiority, and active discouragement of Haskins’
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[sic] proposed solution.” (Appeal Br. 18.) Appellants point to ^fl[ 64 and 65
of Templer as evidence that Templer’s method yields twice as much DNA as
Hawkins’ method. (Id.)
This argument is unpersuasive. First, the Hawkins patent cited by
Templer (U.S. 5,898,071) is not the Hawkins patent relied on by the
Examiner (U.S. 5,705,628) and it is unclear from the description in Templer
how the methods disclosed in the two patents compare. Even assuming the
two Hawkins methods are comparable, as the Examiner has noted (Ans. 16),
Templer’s improved results provide additional reason to modify the method
of Hawkins ’628 to include the ethanol used in Templer’s method with a
reasonable expectation that doing so would yield improved yield of DNA.
Appellants next argue that “Templer directs the skilled artisan away
from the expressly high salt concentrations of Hawkins [’628] (2.5M) and
Hawkins [NAR] (2.5M NaCl), and from the salt concentrations of the
present claims.” (Appeal Br. 19.) Appellants cite Templer’s disclosure of
using salt concentrations of 0.1M to 0.5M. (Id.)
Again, however, the rejection is not based on physically combining
the different binding buffers disclosed in the references into a single
solution, but on modifying the binding buffer disclosed by Hawkins ’628 to
also include Tween 20 and ethanol. Templer provides a reason to include at
least 10% ethanol in the binding buffer of Hawkins ’628 because it teaches
that adjusting the alcohol concentration of a composition comprising
paramagnetic particles and nucleic acids is one way to control binding of the
nucleic acids to the particles. (Templer 116.) Templer also teaches that at
least 10% ethanol provides a suitable condition for binding nucleic acids to
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paramagnetic particles. (Id. 124.) Thus, it would have been obvious to
modify the binding buffer of Hawkins ’628 to include at least 10% ethanol
in order to provide suitable conditions for binding of nucleic acids to
paramagnetic particles.
Finally, Appellants argue that “the unpredictable nature of the far
greater than expected nucleic acid yields of the claimed methods cannot be
reasonably questioned. Example 1, Table 1 shows that optimized levels of
polyoxyethylene sorbitan monolaurate, ethanol, and NaCl result in
dramatically different yields.” (Appeal Br. 20.) Appellants also argue that
“[njothing in the cited references teaches or suggests the optimized critical
ranges of the application[’]s Examples as claimed” (id.) and “[w]hen one
considers that the claims recite specific concentrations of the ingredients and
demonstrates both unexpected success within the range, and failure below
and above the range, the non-obviousness cannot be clearer.”
These arguments are also unpersuasive. The cited references all
disclose binding buffers for use in purification methods like that of claim 1.
The cited references also disclose ranges for each of the components of the
binding buffer that overlap or encompass the amounts recited in claim 1:
0.5M to 5.0M salt (Hawkins ’628), 50 to 100 vol. % ethanol (Templer), and
1% to 25% of a detergent such as Tween 20 (Gundling). Thus, the general
conditions recited in claim 1 were all known in the art for use in similar
procedures, and
“it is not inventive to discover the optimum or workable ranges
by routine experimentation.” In reAller, 220 F.2d 454, 456, 105
USPQ 233, 235 (CCPA 1955). Only if the “results of optimizing
a variable” are “unexpectedly good” can a patent be obtained for
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the claimed critical range. In re Antonie, 559 F.2d 618, 620, 195
USPQ 6, 8 (CCPA 1977).
In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997).
Appellants argue that the Specification’s examples show unexpected
success, but unexpected results must be shown in comparison to the closest
prior art. In re Baxter TravenolLabs., 952 F.2d 388, 392 (Fed. Cir. 1991)
(“[W]hen unexpected results are used as evidence of nonobviousness, the
results must be shown to be unexpected compared with the closest prior
art.”). Here, Hawkins ’628 exemplifies a binding buffer comprising 20%
PEG 8000 and 2.5MNaCl. (Hawkins ’628 9:31 to 13:31.) Appellants do
not point to any examples in the Specification that include a comparison of
the binding buffer recited in claim 1 with the binding buffer of Hawkins
’628 or any other binding buffer from the cited references. Thus, Appellants
have not shown that the method of claim 1 is unexpectedly superior
compared to the closest prior art. Although Appellants characterize the
Specification as showing “the surprising and unpredictable nature of the far
greater than expected nucleic acid yields of the claimed methods” (Reply
Br. 5), “[attorney’s argument in a brief cannot take the place of evidence.”
In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974).
Claims 2—10 and 24—31 have not been argued separately and therefore
fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm the rejection of claims 1—10 and 24—31 under 35 U.S.C.
§ 103(a) based on Hawkins ’628, Hawkins NAR, Templer, Deggerdal, and
Gundling.
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TIME PERIOD FOR RESPONSE
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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