Ex Parte Wagner et al

Board of Patent Appeals and Interferences

Sep 7, 2010

10112840 (B.P.A.I. Sep. 7, 2010)

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.
10/112,840 03/29/2002 Peter Wagner 020144-001901US 5560
20350 7590 09/07/2010
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER
EIGHTH FLOOR
SAN FRANCISCO, CA 94111-3834
EXAMINER
YANG, NELSON C
ART UNIT PAPER NUMBER
1641
MAIL DATE DELIVERY MODE
09/07/2010 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte PETER WAGNER, DANA AULT-RICHE,
STEFFEN NOCK, and CHRISTIAN ITIN
____________

Appeal 2010-004420
Application 10/112,840
Technology Center 1600
____________

Before RICHARD E. SCHAFER, ROMULO H. DELMENDO, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL1

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
Appeal 2010-004420
Application 10/112,840

2
This is a decision on appeal under 35 U.S.C. § 134 by the Patent
Applicants from the Patent Examiner’s rejections of claims 5-31, 42-44, 47,
51, 53, and 60-62. The Board’s jurisdiction for this appeal is under 35
U.S.C. § 6(b). We affirm all rejections.

STATEMENT OF THE CASE.
Claim 5, the only independent claim on appeal, is directed to an array
of proteins on a substrate. The Patent Examiner rejected the claims as
obvious under five different grounds as follows:
1. Claims 5-8, 10-13, 17, 22, 23, 26-29, 31, 42-44, and 53 under 35
U.S.C. § 103(a) as obvious in view of Olinger2 and Pirrung3 (Answer 3);
2. Claims 9, 47, 51, and 60-62 under 35 U.S.C. § 103(a) as obvious in
view of Olinger, Pirrung, and Driedger4 (id. at 7);
3. Claim 14-16 under 35 U.S.C. § 103(a) as obvious in view of
Olinger, Pirrung, and Wagner5 (id. at 8);
4. Claims 18-20, 24, and 25 under 35 U.S.C. § 103(a) as obvious in
view of Olinger, Pirrung, and Bamdad6 (id. at 9); and
5. Claim 21 under 35 U.S.C. § 103(a) as obvious in view of Olinger,
Pirrung, and Turner7 (id. at 11).

2 U.S. Patent No. 5,466,589 (issued Nov. 14, 1995) to Jill M. Olinger et al..
3 U.S. Patent No. 5,143,854 (issued Sept. 1, 1992) to Michael C. Pirrung et
al..
4 U.S. Patent No. 5,643,948 (issued July 1, 1997) to Paul E. Driedger et al..
5 Wagner et al.,” Formation and in Situ Modification of Monolayers
Chemisorbed on Ultraflat Template-Stripped Gold Surfaces,” Langmuir,
11:3867-75, 1995.
6 U.S. Patent No. 5,620,850 (issued Apr. 15, 1997) to Cynthia C. Bamdad et
al..
7 U.S. Patent No. 5,948,621 (issued Sept. 7, 1999) to David C. Turner et al..
Appeal 2010-004420
Application 10/112,840

3
Claim 5 is representative and reads as follows:
An array of proteins, comprising:
(a) a substrate; and
(b) a plurality of patches arranged in discrete known regions on
said substrate, wherein each of said patches comprises an
immobilized protein with a known sequence, wherein at least 9
different proteins are immobilized on at least 9 different patches
of the plurality of patches, wherein the array comprises 100 or
more protein patches within an area of 1 cm2, and wherein the
proteins are functionally related or suspected of being
functionally related, structurally related or suspected of being
structurally related, or members of the same protein family.

OBVIOUSNESS IN VIEW OF OLINGER & PIRRUNG
Statement of the Issues
Background
Claim 5 is directed to an array of proteins comprising (a) a substrate
and (b) protein patches arranged in discrete known regions on the substrate.
The claim requires “at least 9 different proteins . . . immobilized on at least 9
different patches of the plurality of patches, wherein the array comprises 100
or more protein patches within an area of 1 cm2.” The proteins are also
recited to be functionally related, suspected of being functionally related,
structurally related, or members of the same protein family.
The Examiner found that Olinger described a protein array with
protein patches immobilized on a substrate, where different proteins could
be arranged on the substrate (Answer 4). The Examiner acknowledged that
Olinger did not describe an array with 9 different proteins on 9 different
patches as required by claim 5, but found that Pirrung taught protein arrays
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with more than 106 different proteins, meeting this claim limitation (id.).
The Examiner reasoned:
it would have been obvious to one of ordinary skill in the art at
the time of the invention to have up to 106 different
recombinant proteins immobilized on different discrete known
regions in the method of Olinger, as Pirrung et al. suggests that
one of ordinary skill in the art at the time of the invention
would have been motivated to do so in order to screen large
numbers of polymers for biological activity.
(Id. at 5.)

Issues
1. Does Olinger alone, or in combination with Pirrung, enable protein
arrays with “at least 9 different proteins . . . immobilized on at least 9
different patches of the plurality of patches, wherein the array comprises 100
or more protein patches within an area of 1 cm2” as recited in claim 5 or
1000 different proteins as in claim 43?
2. Would modifying Olinger’s coated substrate with at least 9
different proteins “render Olinger et al.’s device inoperative” and
“unsatisfactory for its intended purpose” (App. Br. 7)?
3. Would persons of ordinary skill in the art have had reason to
combine Olinger’s “phase grating [optical] device” with Pirrung’s array
which has “nothing to do with the optical device” (App. Br. 9 & 11)?

1. Enabling disclosure issue
Legal Principles
“References relied upon to support a rejection under 35 USC 103
must provide an enabling disclosure, i.e., they must place the claimed
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invention in the possession of the public.” In re Payne, 606 F.2d 303, 314
(CCPA 1979).
“The invention disclosed in a patent is presumed to be operative
because the patent enjoys a statutory presumption of validity, 35 U.S.C. §
282, and operativeness is a prerequisite to validity, 35 U.S.C. § 101. An
inoperative device lacks the utility which is required by statute.” In re
Spence, 261 F.2d 244, 246 (CCPA 1958.)
35 U.S.C. 282. Presumption of validity; defenses
A patent shall be presumed valid. . . The burden of
establishing invalidity of a patent or any claim thereof shall rest
on the party asserting such invalidity.

Facts
1. Olinger teaches that different mutant proteins can be immobilized on the
same substrate (Olinger, col. 3, ll. 49-50).
2. Olinger teaches that the “mutant protein can be applied to the substrate as
a solution by immersion, by spin coating, by application with a doctor blade
and by similar techniques.” (Id. at col. 6, ll. 12-14.)
3. Claim 5 of Olinger is drawn to a coated substrate with a plurality of
mutant heme proteins and “a second mutant protein immobilized thereon.”
(Id. at col. 23.)
4. Pirrung describes a lithographic technique for synthesizing polypeptide
arrays on a substrate using monomers with “photoremovable groups.”
(Pirrung, Abstract; col. 3, ll. 5-33.)
5. Light is directed to “relatively small and precisely known locations on the
substrate,” enabling large numbers of peptides of known sequence to be
synthesized on the substrate (id. at col. 3, ll. 34-41 & col. 4, ll. 10-12).
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6. The arrays can be used for “screening large numbers of polymers for
biological activity,” such as for receptor binding (id. at col. 3, ll. 39-44; col.
8, ll. 34-45).
7. Pirrung describes an example with 16 different amino acid sequences
(peptides) synthesized on a glass substrate (id. at col. 29, ll. 24-31).
8. Pirrung tested the ability the peptides to bind antibodies. Pirrung
reported:
The sequence YGGFL is clearly most strongly recognized. The
sequences YAGFL and YSGFL also exhibit strong recognition
of the antibody. By contrast, most of the remaining sequences
show little or no binding. The four duplicate portions of the
slide are extremely consistent in the amount of binding shown
therein.
(Id. at col. 29, ll. 50-56.)
9. Pirrung’s claim 1 recites a step of forming at least 100 different
polypeptides on a surface (id. at col. 32, ll. 8-10).
10. Pirrung’s claim 11 recites a step of synthesizing 106 different peptides
on 106 preselected regions (id. at col. 32-33).

Analysis
Obviousness under section 103 requires that the prior art provide an
enabling disclosure of the claimed invention. In re Payne, Durden, and
Weiden, 606 F.2d at 314. In this case, Appellants contend that the cited
Olinger and Pirrung patents did not enable persons of ordinary skill in the art
to have made the claimed protein array with “9 different proteins . . .
immobilized on at least 9 different patches” where “the array comprises 100
or more protein patches.”
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Olinger explicitly disclosed that different mutant proteins can be
immobilized on the array substrate (F1). Olinger also described several
techniques for immobilizing proteins on substrate surfaces (F2) as did
Pirrung (F4). Thus, sufficient evidence was provided by the Examiner to
establish an enabling disclosure for the purpose of section 103, shifting the
burden to Appellants to provide rebuttal arguments or evidence.
Appellants have not introduced evidence that the techniques described
by Olinger and Pirrung would not work to produce an array with patches of
at least nine different proteins. Nor have Appellants provided a scientific
basis upon which to doubt that Olinger’s explicit disclosure of various
immobilization techniques would not enable the ordinary skilled worker to
produce an array of different proteins as recited in claim 5.
Furthermore, claim 5 of Olinger is directed to a coated substrate with
a plurality of mutant heme proteins and “a second mutant protein
immobilized thereon.” (F3.). Thus, claim 5 of Olinger would reasonably be
interpreted to read on at least two different proteins on the same substrate.
As a patent claim is presumed valid and operative, Appellants have the
burden of showing that it is not, i.e., not enabled for immobilizing at least
two different proteins on the substrate surface. Appellants have not met this
burden.
In addition to Olinger, Pirrung describes how to create arrays with as
many as 106 different peptides (F4, F5, F7, F9, & F10). Appellants assert
this disclosure is defective because “significant cross-reactivity would occur
and the proteins would bind to more than 1 peptide” (App. Br. 6).
Pirrung discloses that peptides of different, but related sequence, may
react with the same antibody (F8). However, we do not see how this casts
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any doubt on the operability of Pirrung or its application to Olinger. First,
the instant claims do not exclude the claimed 9 different immobilized
proteins from reacting or cross-reacting with the same protein or antibody.
Secondly, Pirrung’s peptides did not all show the same reactivity – with
some showing strong recognition and others showing little or no binding
(F8). Cross-reactivity and different binding affinities between peptides and
antibodies is expected and in no way denigrates the function of Pirrung’s
arrays. To the contrary, it shows the sensitivity of Pirrung’s array in
detecting strong binding, as well as little or no binding.

2. Proposed Modification Would Render Olinger Inoperable
Facts
11. The Olinger patent describes its invention as relating to coated
substrates employing oriented layers of biological macromolecules (Olinger
col. 1, l. 17-20).
12. Olinger states that systems which utilize layers of proteins coupled to
carriers are well known for many purposes, including antigen or antibody
purification and assays (id. at col. 1, ll. 42-45).
13. Olinger states that its invention can be used to control molecular
interactions and recognition events involving protein binding (id. at col. 2, ll.
48-51).
14. Olinger describes two embodiments: 1) a substrate with a uniform
protein surface; and 2) “[a]lternatively” a coated substrate “obtained by
immobilizing different mutant proteins on the substrate.” (Olinger, col. 3, ll.
35-51).
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15. Olinger discloses that its coated substrate has many applications,
including its use as a phase grating (id. at col. 12, l. 50 to col. 13, l. 5).
16. The Examiner found that “Olinger et al. provides an example where
three mutant cytochrome b5 proteins were immobilized for examining
protein-protein interactions (columns 19-20, example 3).” (Answer 4.)

Analysis
Appellants contend that modifying Olinger’s phase-grating device
with at least 9 different proteins would “render Olinger et al.’s device
inoperative” and “unsatisfactory for its intended purpose.” (App. Br. 7.)
Appellants argue that the modified “phase-grating would not have uniform
optical properties due to the different materials forming the phase grating.”
(Id. at 8.)
The phase-grating embodiment described in the Olinger patent is not
the only device disclosed by Olinger. To the contrary, Olinger explicitly
describes an alternative embodiment in which in which different mutant
proteins are immobilized on the same substrate (F14). The Examiner found,
and Appellants did not dispute, that Olinger had an example in which
different immobilized proteins were used to examine protein-protein
interactions (F16). Consequently, while it might be true that “the proteins
would no longer form a phase grating” when different proteins were
included (App. Br. 8), there is express disclosure of other embodiments in
Olinger in which different proteins are present on the same substrate. In
sum, Appellants’ argument focused on one specific embodiment of Olinger,
ignoring another embodiment expressly relied upon by the Examiner in
rejecting the claims.
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3. Reason to Combine
Legal principles
An 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).

Analysis
Appellants contend that persons of ordinary skill in the art would not
have had reason to combine Olinger’s “phase grating [optical] device” with
Pirrung’s array “which has nothing to do with the optical device” (App. Br.
9 & 11).
Appellants’ position is not supported by the evidence. Olinger’s
disclosure is not limited to phase-grating devices with a single uniform
protein coating (F14). There is express disclosure, undisputed by
Appellants, of coated substrates with different proteins, as well as the use of
coated substrates to study protein-protein interactions (F16). In addition to
this, Olinger, in describing the prior art, acknowledges that coated substrates
had been used in purification and assay methods (F12). Olinger also states
that its device can be used to control molecular interactions and recognition
events involving protein binding (F13). We have not been directed to any
basis to conclude that the Olinger patent is singularly restricted to phase-
grating devices. Rather, when the patent disclosure is read as a whole,
persons of ordinary skill in the art would have understood that Olinger can
be utilized for purposes that protein arrays are generally used for, including
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assays as described in the Pirrung patent. Appellants have simply read
Olinger too narrowly, overlooking explicit broad disclosure suggesting many
uses for the Olinger arrays.
Appellants also argue that “none of the end products mentioned by
Olinger et al. would benefit from having at least 9 or 106 different proteins.
Accordingly, there is no motivation to modify Olinger et al. in the manner
proposed by the Examiner.” (App. Br. 9.)
Once again, we conclude this argument is based on the factual error
that Olinger’s sole disclosure is of a phase-grating device with a uniform
protein pattern. Olinger generally describes its devices for controlling
molecular interactions or recognition event involved in protein binding
(F13), more specifically describes coated substrates for assay and
purification techniques (F12), and has an example of examining protein-
protein interactions with different proteins (F16).
Appellants have not successfully rebutted the Examiner’s conclusion
that utilizing nine different proteins on a substrate would have been obvious
in view of the aforementioned teachings in Olinger and those of Pirrung.
Both Olinger and Pirrung clearly taught the merits of substrates with
different proteins. In our view, any number of different proteins on a
substrate from 2 to 106 would have been an obvious choice because the
coated substrate is been used precisely for the purposes disclosed in the prior
art.
OBVIOUSNESS REJECTIONS 2-5
Appellants do not challenge rejections 3-5. As we find no deficiency
in the Examiner’s findings or determinations, we affirm the rejections for the
reasons stated by the Examiner.
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For rejection 2, Appellants contend that the “Office Action does not
provide evidence that any of [the cited] references teach or suggest an array
of kinases” (App. Br. 12) – apparently a reference to claim 47, which recites
that the “proteins [immobilized on the substrate of claim 5] are kinases.”
Appellants argue that it is not possible to use Pirrung’s method to
make an array of kinases since it is not likely that “one would identify
peptides of 5 amino acids or less that bind specifically to at least 9 different
kinases.” (Id.)
This argument is not persuasive. The Specification discloses that
“immobilized proteins may be just fragments of different members of a
protein family.” (Spec. 15: 15-16.) Thus, we do not interpret claim 47 to
require that the entire kinase protein is immobilized on the surface.
Appellants have not presented evidence that Pirrung’s technique would not
work to make an array of kinase fragments.
Appellants’ argument that Pirrung’s method is unlikely to “identify
peptides of 5 amino acids or less that bind specifically to at least 9 different
kinases” is unpersuasive. The Examiner’s rejection as set forth on pages 7-8
of the Office Action, which we adopt as our own, is based on immobilizing
protein kinases to Olinger’s substrate, not binding of peptides to kinases.

SUMMARY
The obviousness rejection of claim 5 is affirmed. Claims 8, 10-13, 17,
22, 23, 26-29, 31, 42-44, and 53 fall with claim 5 because separate reasons
for their patentability were not provided. 37 C.F.R . § 41.37(c)(1)(vii).
The obviousness rejections of claims 9, 14-16, 18-21, 24, 25, 47, 51,
and 60-62 are affirmed.
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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

KMF

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