Ex Parte Calatzis et al

Patent Trials and Appeals Board

Jun 10, 2019

12522364 - (D) (P.T.A.B. Jun. 10, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/522,364 03/10/2010
46002 7590 06/12/2019
JOYCE VON NATZMER
A GRIS & VON NA TZMER LLP
43 West 43rd Street, Suite 104
New York, NY 10036-7424
FIRST NAMED INVENTOR
Andreas Calatzis
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
3024-160 9177
EXAMINER
TSAY,MARSHAM
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
06/12/2019 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):
uspto-mail@NATZMER-LAW.COM
eofficeaction@appcoll.com
46002 © avn-law .com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANDREAS CALATZIS, MARTIN GLAUNER,
AXEL SCHUBERT, and MAX KESSLER
Appeal2018-006559
Application 12/522,364
Technology Center 1600
Before DEMETRA J. MILLS, ERIC B. GRIMES, and
DAVID COTTA, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a). The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
Appeal2018-006559
Application 12/522,364
STATEMENT OF CASE
The pending claims are directed to a container for use in serum testing,
and a method of using that container for serum testing. Claims 16, 21. The
glass vial used in the serum testing may be coated with a surface covering.
Spec. 1 7. In this embodiment
possible coagulation activation in the test liquid by the glass surface is
excluded, while the superior sealing properties of the glass material
when compared to plastic material are still used. The similar
effect of suppressing possible coagulation activation in the
test liquid by the glass surface can be realized by covering
the glass surface ( or at least the inner portion of the glass
surface) with a layer of one or more substances that are not
able to activate coagulation if they are in contact with blood or blood
components.
Spec. 17.
The following claims are representative.
16. A container, comprising an undivided cup, wherein
the undivided cup comprises a co-lyophilized composition
comprising following constituents:
(i) at least one activator of coagulation;
(ii) a calcium salt in an amount of 1-lOOµmol/ml,
sufficient to ensure recalcification of the test liquid;
(iii) a stabilizer;
(iv) optionally one or more inhibitors and coagulation
factors or activated coagulation factors,
wherein the co-lyophilized composition comprises 10%
or less by weight of a liquid, and wherein the container (a) has a
form that reduces its inner lateral profile from a top opening of
the container to a closed bottom of the container and (b) is
made out of (i) glass and a plastic insert (ii) glass having a
surface covering, wherein the surface covering is a layer of one
or more substances that are not able to activate coagulation if
they are in contact with blood or blood components.
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21. A method of performing a viscoelastic analysis on a
test liquid, comprising:
a.) providing a container which has a form that reduces
its inner lateral profile from a top opening of the container to a
closed bottom of the container and is made out of (i) glass and
plastic, wherein the container is designed so that coagulation
activation in the test liquid by any glass surface of the container
is excluded or (ii) glass having a surface covering, wherein the
surface covering is a layer of one or more substances that are
not able to activate coagulation if they are in contact with blood
or blood components, wherein the container comprises a
diagnostic co-lyophilized composition comprising following
constituents:
(i) at least one activator of coagulation;
(ii) a calcium salt in an amount of 1-1 OOµmol/ml,
sufficient to ensure recalcification of the test liquid;
(iii) a stabilizer;
(iv) optionally one or more inhibitors and coagulation
factors or activated coagulation factors,
wherein the co-lyophilized composition comprises 10%
or less by weight of a liquid and is present in an amount
sufficient for performing one single viscoelastic analysis of the
test liquid;
b.) directly adding a test liquid into said container,
wherein the diagnostic colyophilized composition contained
therein is dissolved in said test liquid to provide a mixture;
c.) optionally, transferring the mixture into an apparatus
suitable for performing a viscolelastic analysis; or
putting the container into an apparatus suitable for
performing a viscolelastic analysis; and
d.) performing the viscoelastic analysis of said mixture.
Cited References
Bums us 4,529,614
3
July 16, 1985
Appeal2018-006559
Application 12/522,364
Zuckerman US 5,223,227 June 29, 1993
Baugh '712 US 5,972,712 Oct. 26, 1999
Brucato et al. US 6,100,072 Aug. 8, 2000
Cohen et al. US 6,537,819 B2 Mar. 25, 2003
Baugh '563 WO 98/49563 Nov. 5, 1998
Benecky WO 02/079375 Al Oct. 10, 2002
(Corresponding to US 2003064414)
Sigma Aldrich Catalog, T786, T782 (2001 ).
BD Vacutainer® Tube Guide (2005).
Grounds of Rejection 1
1. Claims 16-17 and 19--20 are rejected under pre-AIA 35 U.S.C.
§I03(a) as being unpatentable over Brucato in view ofBenecky,[2]
Sigma and Bums.
2. Claims 2--4, 6, 11, 15, 21-28, 33, 35-37, 39--40, and 46 are
rejected under pre-AIA 35 U.S.C. § I03(a) as being unpatentable
over Brucato in view of Benecky, Sigma, Bums, Zuckerman, and
Cohen.
3. Claim 9 is rejected under pre-AIA 35 U.S.C. § I03(a) as being
unpatentable over Brucato in view of Benecky, Sigma, Bums,
Zuckerman, Cohen and Baugh '712.
1 The Examiner has stated that "Claim(s) 2-11, 15-17, 19--28, 33, 35--40, 46
(partially) is/are rejected." Non-final Action mailed April 5, 2017, page 1.
However, none of the rejection in the Non-final Action or in the Answer
includes any of claims 5, 7, 8, 10, or 3 8.
2 The Examiner indicates that Benecky, US 2003064414, corresponds to
WO 02079375, and the Examiner appears to refer to paragraph numbers in
US 2003064414 in the Answer.
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Application 12/522,364
FINDINGS OF FACT
The Examiner's findings of fact are set forth in the Answer at pages
3-24. The following facts are highlighted.
1. Brucato disclose a reagent based on recombinant tissue factor (TF)
with defined phospholipids and other stabilizers, where the reagent is
in a liquid or lyophilized formulation, and is useful for determining at
least fibrinogen levels, percent coagulation factor activity,
prothrombin time (PT), percent PT activity, and PT ratio, in a patient
sample using clinical coagulation instruments ( col. 2 lines 22-30, col.
2, line 65 to col. 3, line 5). At col. 10, lines 12--40, Brucato disclose a
lyophilized TF reagent composition comprising recombinant TF,
calcium chloride 10 mM, dextran 5%, glycine 5%, albumin 0.3%.
2. Brucato's TF reagents have many applications (see FFl), where the
reagent activates the extrinsic pathway of coagulation ( col. 7 lines 18-
23, col. 7-8).
3. Brucato et al. disclose preparing the lyophilized TF reagent
composition and further combining said lyophilized TF reagent
composition and stabilizers with a blood sample to measure
PT/fibrinogen levels/clot formation (col. 10, lines 13-29, col. 10, lines
55---65, col. 14, lines 13-20, col. 12 lines, 58---67).
4. Brucato et al. disclose that the TF formulation comprising
phospholipids, other stabilizers including buffers, and calcium
chloride salt, can be in a single vial reagent, where the TF reagent is in
lyophilized form (col. 3, lines 6-33, col. 7, lines 12-14).
5. Benecky et al. provide methods to rapidly assess the overall coagulant
properties of blood and blood products by inhibiting the intrinsic
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contact pathway in vitro and stimulating activation of the extrinsic
activation pathway with at least one procoagulant agent. The method
enables the measurement of blood coagulation via the extrinsic
pathway, which is more representative of the in vivo state of
coagulation (abstract, p. 5).
6. Benecky discloses that the intrinsic pathway can be inhibited by
contacting the whole blood or blood product sample with a surface
having low thrombogenic activity; examples of surfaces having low
thrombogenic activity include plastic, glass, siliconized glass; [3] the
contact can be performed during collection, storage, or handling of the
whole blood or blood product sample. The whole blood sample may
be collected in the presence of an anticoagulant, the anticoagulant will
block the extrinsic or common pathways. Benecky, p. 16. The effect
of the anticoagulant in the blood sample must be reversed at the time
blood coagulability or clotting time is measured. This is
accomplished by the addition of calcium salt. Benecky p. 16; Ans. 4-
5.
7. Benecky discloses a composition comprising recombinant TF,
calcium salt, and albumin, further comprises a low molecular weight
heparin (LMWH) (an optional inhibitor), to assess coagulation of a
blood sample. Benecky, p. 20.
3 The definition of "siliconized ": treated or coated with a silicone
// siliconized glassware. https://www.merriam-webster.com/
dictionary/ siliconized
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8. Benecky discloses that any number of available procedures for
measuring blood clotting may be used. Instruments suitable for this
purpose include for example, all instruments that measure mechanical
impedance caused by initiation of a clot, the reagents that initiate
clotting or affect clotting times may be presented in various forms,
including but not limited to solutions, lyophilized or air-dried forms.
Benecky, p. 17. The containers or vessels, including test tubes,
comprising the at least one procoagulant (i.e. TF) are used with
instruments to measure the clotting time and/or viscoelastic properties
of a blood sample, including a thromboelastograph device (Benecky,
p. 5, p. 6-9 working examples).
9. Benecky discloses test kits for determining coagulability, comprising
collection tubes having low thrombogenic activity that contain at least
one procoagulant of the extrinsic pathway, where the vessel further
comprises an inhibitor of coagulation, and calcium salt to reverse the
effect of the inhibitor ([0035], [0036], [0037], [0062]).
10. Sigma discloses glass vials/containers having a form that reduces its
inner lateral profile from a top opening of the container to a closed
bottom of the container for use in collecting or storing biological
samples/fluids were readily available (Sigma catalog 2001: pages
T782, T786). The glass V-vials are graduated, comprise plastic tops
for storage and/or have plastic-faced polymeric tops.
11. Bums discloses methods for coating substrates such as plastics and
glass to impart anticoagulant and hydrophobic properties to the
substrate, and to substrates so coated. The method is particularly
useful in coating the internal surfaces of blood test vessels for
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receiving blood samples for subsequent testing. The method imparts
the desired properties to the vessel in a single step by combining
silicone containing material and anticoagulant with a water vehicle,
followed by air drying (at least abstract, col. 1-3).
12. Zuckerman discloses a cup that can be used for blood coagulation
tests in instruments, such as a thromboelastograph instrument ( col. 1-
2) and Cohen et al. disclose a method and apparatus for measuring
blood clotting characteristics that uses the cup of Zuckerman ( col. 1-
2, also detailed description).
13. Zuckerman discloses that the inner surface of the cup tapers outward
quickly near the top. The profile of the cup appears to reduce from the
opening to the bottom (col. 3 lines 11-20, Fig. 2).
14. Baugh discloses a composition that is equivalent to Brucato and
Benecky, in regards to the components that it comprises, and that this
composition can also be used in a method to determine and/or
measure clotting time in a blood sample ( col. 9 lines 17-25, col. 19
lines 47-67). Baugh discloses that heparinase can be included in the
composition as a heparin inhibitor (col. 20 lines 1-2).
15. The Specification states that, "The diagnostic composition or reaction
mixture of the present invention comprises constituents, which are per
se known in the art." Spec. 11.
PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F .2d 1422, 1427
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(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007).
Claim Interpretation
Claim 16 includes the following language:
Wherein the container ... (b) is made out of (i) glass and a plastic
insert (ii) glass having a surface covering, wherein the surface covering is a
layer of one or more substances that are not able to activate coagulation if
they are in contact with blood or blood components.
We interpret the above language to mean that subnumerals (i) and (ii)
of claim 16 are alternatives which should have been connected by the term
"or" as in claim 21. This interpretation is consistent with the Specification,
page 16, which states that, "the container 1 might be designed by
combination of two materials, e.g., glass and plastic or glass and a surface
covering." "[D]uring examination proceedings, claims are given their
broadest reasonable interpretation consistent with the specification." In re
Hyatt, 211 F.3d 1367, 1372 (Fed. Cir. 2000).
Obviousness
The Examiner concludes, based on the factual evidence above, that:
It would have been obvious to one of ordinary skill in the art ...
to combine the references and incorporate the lyophilized TF
reagent composition of Brucato et al. into glass vials ... ,
including a glass vial having a form that reduces its inner lateral
profile from a top opening of the container to a closed bottom
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of the container, where the inner surface of said glass vial is
coated with a material that does not activate coagulation, i.e. a
silicone containing material, because it was known in the art
that siliconized glass vials can be used to contain the
compositions and/or samples disclosed by Brucato et al. ... The
motivation to do so is given by the prior art. Brucato et al.
disclose single vial reagents comprising a lyophilized TF
composition comprising stabilizers, calcium chloride 10 mM,
where the reagent activates the extrinsic pathway of
coagulation. It is disclosed that the containers used to contain
the TF formulation should preferably have a surface having low
thrombogenic activity, such as plastic, glass, siliconized glass,
including collection tubes, which would generally be known to
have tapered bottoms (Benecky et al.). Glass V-vials [Sigma,
T786] having plastic-faced polymeric tops were readily
available at the time of the invention and coating glass vials to
inhibit incidental clotting of collected blood samples was also
known.
Ans. 6-7; emphasis added.
Appellants contend that
Bums suggests that his surface forms an anticoagulant/-
organopolysiloxane prepolymer matrix that is mechanically
fixed to the substrate of interest. Thus, with the addition of
blood, the mechanical coating dissolves in the blood to the
extent necessary to impart anticoagulant properties to the
sample, while the organopolysiloxane provides sufficient flow
for the blood to impart hydrophobicity to the surface of the
substrate of interest ( col. 1, lines 53---60).
While Sigma suggests tapered vials, the Examiner has
not provided any argumentation why the person skilled in the
art would select such a tapered vial for Brucato' s reagent.
Appellant further notes that the primary reference,
Brucato, discloses liquid and lyophilized reagents for
determining prothrombin time for determining deficiencies in
the coagulation system (Brucato' s Abstract and Field of the
Invention). Appellant submits that the person skilled in the art
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would not consider modifying a testing vial in which Brucato' s
reagents are used to measure prothrombin time to include an
inner surface covering that is thought to release anticoagulant
into the sample, as such an anticoagulant could compromise the
prothrombin time determination.
App. Br. 10-11. Appellants further argue that, "in Brucato there is no
dissolving of the co-lyophilized composition in said test liquid, but a
dissolving of the co-lyophilized composition in the buffer followed by the
addition of the test liquid." App. Br. 12.
ANALYSIS
Appellants do not provide separate argument for dependent claims
with respect to rejection 1. We select claim 16 as representative claim for
purposes of this rejection. We agree with the Examiner's fact finding,
statement of the rejection and responses to Appellants' arguments as set
forth in the Answer. We find that the Examiner has provided evidence to
support a prima facie case of obviousness. We provide the following
additional comment to the Examiner's argument set forth in the Non-Final
Rejection (mailed April 5, 2017) and Answer.
The cited references support the Examiner's prima facie case of
obviousness. Brucato teaches a lyophilized composition having the same
components as the co-lyophilized composition recited in the claim. In
particular, Brucato discloses preparing a lyophilized TF reagent
composition and combining the lyophilized TF reagent composition and
stabilizers with a blood sample to measure PT/fibrinogen levels/clot
formation (PT; prothrombin time) (col. 10 lines 28-34, lines 55---65, col. 14
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lines 13-20). Brucato further discloses that the lyophilized TF reagent
composition can be in a single vial reagent (col. 7 lines 12-14); therefore,
Brucato reasonably discloses a container comprising a lyophilized TF
reagent composition comprising TF, calcium chloride 10 mM, dextran 5%,
glycine 5%, albumin 0.3%. Ans. 5.
We have interpreted claims 16 and 21, to alternatively require that the
recited container be made of either (i) glass and a plastic insert or (ii) glass
having a surface covering. Thus, in order to meet the claims, the Examiner
need only establish one of the two alternative container conformations.
Benecky teaches that it was well known at the time of the invention in the
blood parameter measurement art to use "a surface having low thrombogenic
activity." Benecky, p. 16. Benecky further discloses:
Examples of surfaces having low thrombogenic activity include
plastic, glass, and siliconized glass. The contact can be
performed during collection, storage, or handling of the whole
blood or blood product sample. By the term "low thrombogenic
activity" as used herein is meant having little or no blood
clotting activity. Preferably, the surface having low
thrombogenic activity will inhibit the whole blood or blood
product sample clotting time from between about 10 to about
3600 seconds longer than a suitable control, more preferably
from about 50 to about 1500 seconds, and even more
preferably, from about 150 to about 1050 seconds longer than
the control.
Benecky, p. 16; italicized emphasis added. The Examiner concludes that
It would have been obvious to one of ordinary skill in the art at
the time that the invention was made to combine the references
and incorporate the lyophilized TF reagent composition of
Brucato et al. into glass vials known and available in the art at
the time of the invention, including a glass vial having a form
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that reduces its inner lateral profile from a top opening of the
container to a closed bottom of the container, where the inner
surface of said glass vial is coated with a material that does not
activate coagulation, i.e. a silicone containing material, because
it was known in the art that siliconized glass vials can be used
to contain the compositions and/or samples disclosed by
Brucato et al. (instant claim 16). The motivation to do so is
given by the prior art. Brucato et al. disclose single vial
reagents comprising a lyophilized TF composition comprising
stabilizers, calcium chloride 10 mM, where the reagent
activates the extrinsic pathway of coagulation. It is disclosed
that the containers used to contain the TF formulation should
preferably have a surface having low thrombogenic activity,
such as plastic, glass, siliconized glass, including collection
tubes, which would generally be known to have tapered
bottoms (Benecky et al.).
Ans. 9. We agree with the Examiner's stated prima facie case of
obviousness.
Appellants argue that the person skilled in the art would not consider
modifying a testing vial in which Brucato' s reagents are used to measure
prothrombin time to include an inner surface covering, such as that of Bums,
that releases anticoagulant into the sample, as such an anticoagulant could
compromise the prothrombin time determination.
We are not persuaded by Appellants' argument. The claim 16(b)
limitation alternative of a "(ii) glass having a surface covering" form of a
serum vial is known from the combination of Benecky and Sigma.
Therefore, Bums is not required to meet the limitations of claim 16(b )(i). In
particular, at the time of the invention, glass vials/containers with plastic
tops, having a form that reduces its inner lateral profile from a top opening
of the container to a closed bottom of the container for use in collecting
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biological samples/fluids were readily available (Sigma catalog 2001, pp.
T782, T786). It was also known in the art that it was desirable for serum
containers to have surfaces with low thrombogenic activity. Benecky, p. 16;
Ans. 5. According to Benecky, low thrombogenic surfaces, include glass,
plastic and siliconized glass. Benecky, p. 16.
It would have been obvious to one of ordinary skill in the art to select
a serum vial with an insert having a reduced inner lateral profile as taught by
the V-tubes of Sigma. It would have been further obvious to select from the
low thrombogenic tube surfaces, as suggested by Benecky, including
siliconized glass for the surface of the V-vial of Sigma (Sigma, T 786). It
would have been obvious to place the Brucato lyophilized composition,
which corresponds to the composition recited in the claims, in a serum test
vial for serum testing. FF 1, 4.
Put another way, Benecky discloses that siliconized glass has low
thrombogenic activity, and Benecky suggests the use of siliconized glass for
the assessment of whole blood. Abstract. Siliconized glass includes glass
coated with silicone. See, footnote 3 above. Bums also discloses that it was
well known in the art to treat or coat serum vessels with silicone containing
material and anticoagulant. Bums, col. 1, 11. 40-50. Appellants do not
provided evidence ( attorney argument is not evidence), that the presence of
an anticoagulant on the surface of the vial that is intended to prevent random
coagulation - not to change the properties of the substance - would
materially affect the function of Brucato' s co-lyophilized composition.
We agree with the Examiner that
It would have been obvious to one of ordinary skill in the art ...
to combine the references and incorporate the lyophilized TF reagent
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composition of Brucato et al. into glass vials ... , including a
glass vial having a form that reduces its inner lateral profile
from a top opening of the container to a closed bottom of the
container, where the inner surface of said glass vial is coated
with a material that does not activate coagulation, i.e. a silicone
containing material, because it was known in the art that
siliconized glass vials can be used to contain the compositions
and/or samples disclosed by Brucato.
Ans. 7.
Appellants also argue that, "in Brucato there is no dissolving of the
co-lyophilized composition in said test liquid, but a dissolving of the co-
lyophilized composition in the buffer followed by the addition of the test
liquid." App. Br. 12. We agree with the Examiner that Brucato discloses
that the lyophilized formulation may be in a single vial reagent ( col. 7 lines,
12-14); therefore, it would be obvious that a test sample, such as blood, can
be added directly to a vial containing the lyophilized TF reagent and
dissolve the lyophilized composition. Ans. 22.
Appellants rely on their arguments presented for rejection 1 to
challenge obviousness rejections 2 and 3. We are not persuaded for the
reasons set forth above. App. Br. 11. Any remaining arguments of
Appellants have been addressed by the Examiner in the Answer, and we
adopt the Examiner's responses as our own.
Obviousness rejections 1-3 are affirmed for the reasons of record.
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CONCLUSION OF LAW
The cited references support the Examiner's obviousness rejections 1-
3, which are affirmed for the reasons of record. All pending, rejected claims
fall.
AFFIRMED
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