Ex Parte Tsinberg

Board of Patent Appeals and Interferences

Mar 16, 2010

10921073 (B.P.A.I. Mar. 16, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte PAVEL TSINBERG
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Appeal 2009-013438
Application 10/921,073
Technology Center 1600
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Decided: March 16, 2010
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Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, 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
microarrays with minimal background binding. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
Appeal 2009-013438
Application 10/921,073

Statement of the Case
Background
“Non-specific binding of proteins to a microarray substrate increases
the background noise when the microarray is imaged or the signals
generated on the microspots are otherwise read” (Spec. 2, ll. 6-8).
The Specification teaches that “[i]t has now been found that by
grafting a polymer having a multifunctional hydrophilic backbone onto a
substrate surface so as to coat such surface, and crosslinking such polymer to
a substantial degree via linking to polyfunctional isocyanate molecules, there
will be created a very effective protein-resistant microarray substrate
surface” (Spec. 4, ll. 21-25). According to the Specification, “[s]uch
coatings will have improved performance in eliminating background noise”
(Spec. 4, ll. 25-26).
The Claims
Claims 30 and 37-42 are on appeal. Claims 30 and 37 are
representative and read as follows:
30. A microarray that has minimal background binding, which
microarray is made by:
providing a glass substrate having a flat upper surface which is
derivatized with an aminosilane to attach amino groups that are
isocyanate-reactive,
applying a multifunctional protein-resistant coating upon at
least an assay region of said surface by coating with a solution of a
polyurethane prepolymer comprising an isocyanate end-capped
polyethylene glycol (PEG), a polypropylene glycol (PPG) or a
copolymer thereof having a molecular weight between about 500 and
30,000 Daltons in acetonitrile, which solution contains an effective
amount of a basic catalyst that results in crosslinking said PEG, PPG
or copolymer via urethane bonds to form said crosslinked
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polyurethane polymer, while covalently bonding said polyurethane
polymer to said amino groups on said surface,
curing so said coating is crosslinked such that at least about
10% of said PEG and/or PPG molecules have triple linkages,
affixing a plurality of three-dimensional hydrogel spots to said
protein-resistant polyurethane coating at spaced locations within said
array region, and
linking different organic capture agents of interest into various
of said three-dimensional hydrogel spots.

37. A microarray which comprises:
a glass substrate having a flat upper surface which is derivatized
with an aminosilane to carry amino groups which are isocyanate-
reactive,
a plurality of three-dimensional (3D) microspots at discrete
spatial locations across an array region of said surface, which
microspots contain or are adapted to link directly or indirectly to an
organic capture agent, and
a protein-resistant polyurethane coating which covers the
surface in the array region surrounding the microspots, said
polyurethane coating being multifunctional, comprising hydrophilic
polyolefinic ether backbone polymers, which polyurethane polymers
are crosslinked to a degree of at least about 10% via urethane bonds
which result from a basic catalyst included therein, said coating being
covalently bound to said amino groups on said glass surface via
isocyanate linking.

The prior art
The Examiner relies on the following prior art references to show
unpatentability:
Braatz et al. US 5,175,229 Dec. 29, 1992
Hahn et al. US 6,174,683 B1 Jan. 16, 2001

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The issue1
The Examiner rejected claims 30 and 37-42 under 35 U.S.C. § 103(a)
as being obvious over Hahn and Braatz (Ans. 3-5).
The Examiner finds it obvious to the ordinary skilled artisan to “have
a layer of protein-resistant polyurethane coating as described by Braatz et al.
surrounding the microspots of capture agents, such as that taught by Hahn et
al, in order to prevent artifacts or noise caused by non-specifically bound
analytes” (Ans. 4).
Appellant argues that “Braatz et al does not disclose a coating that one
would choose to use as a protein-resistant coating for the array region of a
microarray surrounding 3D hydrogel microspots” (App. Br. 5). Appellant
argues that Braatz “does not teach a polyurethane coating grafted upon a
surface such that polyolefinic ether backbone polymers are crosslinked to a
substantial degree via isocyanate molecules that form urethane bonds and
also provide free isocyanate groups which covalently bond to the derivatized
flat glass surface” (id.). Appellant argue that “Braatz et al.’s polyurea-
urethane hydrated polymer would be attractive of water and its dissolved
solutes, in contrast to Appellant's polyurethane polymer which . . . is not
hydrated” (id. at 5-6).
In view of these conflicting positions, we frame the obviousness issue
before us as follows:
Has Appellant demonstrated that the Examiner erred in finding that
the combination of Hahn and Braatz render obvious a “microarray that has

1 The Examiner withdrew the 35 U.S.C. § 103(a) rejection over Hahn and
Matthews (Ans. 6).
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minimal background binding” with “a protein-resistant polyurethane
coating” as required by claims 30 and 37?
Findings of Fact
1. Hahn teaches a “polyurethane-based hydrogel biochip
comprising a solid, transparent substrate having active amines on its top
surface, such as a glass substrate treated with silane; a polyurethane-based
hydrogel cell covalently bound to the top surface of the substrate” (Hahn,
col. 4, ll. 50-54).
2. Hahn teaches that “each microdroplet of hydrogel contains a
different biomolecular probe, thereby permitting screening of large numbers
of biomolecular probes in a single reaction. In one preferred embodiment,
the biomolecular probes used in constructing the biochips described herein
are peptide nucleic acid probes” (Hahn, col. 5, ll. 21-26).
3. Hahn teaches that the biochip “uses a polyurethane hydrogel
based on a prepolymer of polyethyleneoxide, or a copolymer of polyethylene
oxide and polypropyleneoxide, capped with water-active diisocyanates and
lightly cross-linked with polyols such that the quantity of isocyanates
present is predictable for example is at most 0.8 meq/g” (Hahn, col. 6, ll. 41-
47).
4. Braatz teaches that the “polyurethane polymer system of this
invention provides hydrated polymer gels with highly desirable properties
which make them particularly well suited for use in the growing field of
biomedical applications for polymers” (Braatz, col. 2, ll. 39-43; emphasis
added).
5. Braatz teaches that “a unique series of crosslinked polyurea-
urethane polymer gels can be formed from high molecular weight isocyanate
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end-capped prepolymers which are substantially comprised of ethylene
oxide units” (Braatz, col. 1, ll. 18-21).
6. Braatz teaches “hydrophilic polyurethane prepolymers and
related crosslinked hydrated polymer gels have been found which are
uniquely characterized by biocompatibility and resistance to nonspecific
protein adsorption” (Braatz, col. 3, ll. 11-15; emphasis added).
7. Braatz teaches that the “hydrated polymers are formed from
polymeric monomer units (the prepolymer units) at least 75% of which are
oxyethylene-based diols or polyols having molecular weights of about 7000
to about 30,000, with essentially all of the hydroxyl groups of these diols or
polyols capped with polyisocyanate” (Braatz, col. 3, ll. 15-20).
8. Braatz teaches that “diols may be capped with diisocyanates
and used in conjunction with crosslinking compounds to form the hydrated
polymers described” (Braatz, col. 4, ll. 8-10).
9. Braatz teaches that “[c]oating a surface normally adsorptive to
protein with a polymer of this invention therefore reduced protein binding
by > 99%” (Braatz, col. 16, ll. 16-18).
10. The Specification teaches that the “protein-resistant polymeric
coating is designed to covalently bind to the organic groups on the
functionalized substrate surface; it has hydrophilic backbone polymers that
are crosslinked to a substantial degree, preferably through urethane or urea
bonds” (Spec. 9, ll. 20-23).
11. The Specification teaches that the “coating can alternatively be
applied across the entire array region . . . [t]hese isocyanate-modified
molecules create a strong urea bond with amino groups on a surface that has
been derivatized with an aminosilate or the like” (Spec. 10, ll. 4-7).
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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
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). As noted by the Court in KSR,
“[a] person of ordinary skill is also a person of ordinary creativity, not an
automaton.” 550 U.S. at 421.
Claim terms are interpreted using the broadest reasonable
interpretation in light of the Specification. See, e.g., In re Hyatt, 211 F.3d
1367, 1372 (Fed. Cir. 2000) (“[D]uring examination proceedings, claims are
given their broadest reasonable interpretation consistent with the
specification.”). Also see In re Morris, 127 F.3d 1048, 1054-56 (Fed. Cir.
1997). (“Absent an express definition in their specification, the fact that
appellants can point to definitions or usages that conform to their
interpretation does not make the PTO's definition unreasonable when the
PTO can point to other sources that support its interpretation.”)
Analysis
Claim 30
Claim interpretation is at the heart of patent examination because
before a claim is properly interpreted, its scope can not be compared to the
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prior art. In this case, Appellant challenges the Examiner’s interpretation of
the phrase “protein-resistant polyurethane coating” as recited in Claims 30
and 37, arguing that “Braatz et al.’s polyurea-urethane hydrated polymer
would be attractive of water and its dissolved solutes, in contrast to
Appellant’s polyurethane polymer which . . . is not hydrated” (App. Br. 5-6).
Appellant argues that Braatz “does not teach a polyurethane coating
grafted upon a surface such that polyolefinic ether backbone polymers are
crosslinked to a substantial degree via isocyanate molecules that form
urethane bonds and also provide free isocyanate groups which covalently
bond to the derivatized flat glass surface” (App. Br. 5).
During prosecution, claim terms are given their broadest reasonable
interpretation as they would be understood by persons of ordinary skill in the
art in the light of the Specification. Therefore, we first turn to the
Specification to determine whether the meaning of the phrase “protein-
resistant polyurethane coating” can be discerned.
The Specification teaches that the “protein-resistant polymeric coating
is designed to covalently bind to the organic groups on the functionalized
substrate surface; it has hydrophilic backbone polymers that are crosslinked
to a substantial degree, preferably through urethane or urea bonds” (Spec. 9,
ll. 20-23; FF 10). The Specification teaches that the “coating can
alternatively be applied across the entire array region . . . [t]hese isocyanate-
modified molecules create a strong urea bond with amino groups on a
surface that has been derivatized with an aminosilate or the like” (Spec. 10,
ll. 4-7; FF 11).
Appellant does not identify any portion of the Specification which
limits the polyurethane coating to exclude the presence of urea bonds, and
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the cited portions of the Specification indicate that urea bonds are
encompassed in the polyurethane coating (FF 10-11).
The Examiner finds that “since the gels of Braatz et al. do comprise
urethane linkages, the limitation is met” (Ans. 6).
We find that the Examiner has the better position here. Claim 30 uses
the “comprising” transitional phrase for the polyurethane prepolymer.
Claim 37 also uses the open “comprising” language. Neither claims 30 and
37 nor Appellant’s Specification excludes compositions with both urethane
and urea bonds. In fact, the Specification is reasonably interpreted to
include compositions with urethane and urea bonds (FF 10-11). The use of
the transitional phrase “comprising” itself indicates that the elements
following the transition may be supplemented by additional elements or
steps and still fall within the scope of the claim. Scanner Technologies Corp.
v. ICOS Vision Systems Corp., N.V., 365 F.3d 1299, 1303 (Fed. Cir. 2004).
Therefore, we find that Claims 30 and 37 encompass the crosslinked
polyurea-urethane polymer gels of Braatz (FF 5).
Appellant argues that “Braatz et al does not disclose a coating that one
would choose to use as a protein-resistant coating for the array region of a
microarray surrounding 3D hydrogel microspots” (App. Br. 5).
We are not persuaded. Hahn teaches that “[i]n one preferred
embodiment, the biomolecular probes used in constructing the biochips
described herein are peptide nucleic acid probes” (Hahn, col. 5, ll. 21-26; FF
2). Thus, as the Examiner notes, an ordinary practitioner would reasonably
be motivated to reduce noise caused by nonspecifically bound peptide
backbones of the peptide nucleic acid probes to the solid support (see Ans.
4). This concern is addressed by Braatz, who teaches that “[c]oating a
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surface normally adsorptive to protein with a polymer of this invention
therefore reduced protein binding by > 99%” (Braatz, col. 16, ll. 16-18; FF
9). The ordinary practitioner would have reasonably used the polyurethane
coating of Braatz to reduce artifactual or non-specific binding of peptide
nucleic acids to the solid support (FF 2, 9).
Appellant argues that “Braatz et al.’s polyurea urethane hydrated
polymer would be attractive of water and its dissolved solutes, in contrast to
Appellant’s polyurethane polymer which . . . is not hydrated” (App. Br. 5-6).
We are not persuaded that Braatz would not function as a polymer
coating because Braatz clearly teaches that the polyurethane coating reduces
protein binding (FF 9). Thus, Appellant’s argument does not provide a
reason which would dissuade the ordinary artisan from using the
polyurethane coating of Braatz with the microarray hybridization hydrogel
of Hahn. See In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (“Where, as
here, the claimed and prior art products are identical or substantially
identical, or are produced by identical or substantially identical processes,
the PTO can require an applicant to prove that the prior art products do not
necessarily or inherently possess the characteristics of his claimed
product.”).
Claim 37
Appellant argues that “Braatz et al discloses hydrated polyurea-
urethane polymer and not Appellant’s claimed protein-resistant polyurethane
coating which surrounds the microspots and is cross-linked to a degree of at
least about 10% with urethane bonds” (App. Br. 6).
We are not persuaded for several reasons. First, as discussed in the
claim interpretation above, Claim 37 encompasses the polyurea-urethane
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polymer of Braatz. Second, as the Examiner correctly notes, the amount of
cross-linking is both an inherent feature of Braatz and a routinely
optimizable variable. Braatz clearly encompasses some degree of
crosslinking, and Braatz teaches that “diols may be capped with
diisocyanates and used in conjunction with crosslinking compounds to form
the hydrated polymers described” (Braatz, col. 4, ll. 8-10; FF 8).
Appellant has simply argued the difference regarding “at least about
10% crosslinking.” The discovery of an optimum value of a results-
effective variable in a known process is normally obvious. In re Antonie,
559 F.2d 618, 620 (CCPA 1977); In re Aller, 220 F.2d 454, 456 (CCPA
1955). Appellant has provided no evidence or argument to rebut the finding
that the amount of cross-linking is a results-effective variable or to
demonstrate unexpected results with the claimed cross-linking amounts.
Conclusion of Law
Appellant has not demonstrated that the Examiner erred in finding that
the combination of Hahn and Braatz render obvious a “microarray that has
minimal background binding” with “a protein-resistant polyurethane
coating” as required by claims 30 and 37.

SUMMARY
In summary, we affirm the rejection of claims 30 and 37 under 35
U.S.C. § 103(a) as obvious over Hahn and Braatz. Pursuant to 37 C.F.R. §
41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 38-42 as these
claims were not argued separately.

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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED

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