Ex Parte Wei et al

Patent Trial and Appeal Board

Jan 10, 2018

13861422 (P.T.A.B. Jan. 10, 2018)

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.
13/861,422 04/12/2013 Tie Q. Wei 2013P06660US 1092
28524 7590 01/12/2018
SIEMENS CORPORATION
INTELLECTUAL PROPERTY DEPARTMENT
3501 Quadrangle Blvd Ste 230
EXAMINER
MARCSISIN, ELLEN JEAN
Orlando, EL 32817 ART UNIT PAPER NUMBER
1678
NOTIFICATION DATE DELIVERY MODE
01/12/2018 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):
ipdadmin.us@siemens.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TIE Q. WEI, WILLIAM BEDZYK, and
ELSA GARCIA1
Appeal 2017-004227
Application 13/861,422
Technology Center 1600
Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and
JOHN G. NEW, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
appellants state that the real party-in-interest is Siemens Healthcare
Diagnostics Inc. App. Br. 2.
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Application 13/861,422
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 15—20. Specifically, claims 15 and 16
stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious
over the combination of Laurie et al. (US 2004/0096900 Al, May 20, 2004)
(“Laurie”), B.W. Hollis, Comparison of Equilibrium and Disequilibrium
Assay Conditions For Ergocalciferol, Cholecalciferol and Their Major
Metabolites, 21(1) J. Steroid Biochem. 81-86 (1984) (“Hollis”), L.M.
Thienpont et al., Standardization of Measurements of 25-hydroxyvitamin D3
and D2, 72(Suppl. 243) Sc and. J. Clin. & Lab. Invest. 41^49 (2012)
(“Thienpont”), Dowd et al. (US 2006/0177873 Al, August 10, 2006)
(“Dowd”), and Bioventix, Product Data Sheet, revised Oct. 2010, 1 page
(“Bioventix”).
Claims 17—20 stand rejected as unpatentable under 35 U.S.C. § 103(a)
as being obvious over the combination of Laurie, Hollis, Thienpont, Dowd,
Bioventix and Singh et al. (US 6,406,667 Bl, June 18, 2002) (“Singh”).2
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants’ invention is directed to methods of adjusting a
contribution of one of two analyte homologs to an amount of signal obtained
2 Claim 15 was also rejected by the Examiner as unpatentable under 35
U.S.C. § 112, first paragraph, as lacking adequate written descriptive
support. Final Act. 3. This rejection has been withdrawn by the Examiner.
Ans. 9.
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in an assay for determining a total amount of the two analyte homologs in a
sample. Abstract.
REPRESENTATIVE CLAIM
Claim 15 is representative of the claims on appeal and recites:
15. A method of determining in a sample a total amount of 25-
hydroxy vitamin D2 and 2 5-hydroxy vitamin D3, the method
comprising:
(a) providing simultaneously in combination in an assay
medium:
(i) a sample suspected of containing 25-hydroxy vitamin
D2 and 2 5-hydroxy vitamin D3,
(ii) an assay antibody capable of binding to 25-hydroxy
vitamin D2 and 25-hydroxy vitamin D3 to form
complexes and a member of a signal producing system
that produces a signal in relation to the amount of 25-
hydroxy vitamin D2 and 25-hydroxy vitamin D3
complexes wherein the member of the signal
producing system is bound to the assay antibody or to
a vitamin D analog that competes with 25-hydroxy
vitamin D2 and 25-hydroxy vitamin D3 in the sample
for binding to the assay antibody, and
(iii) a preferential binding antibody that has a binding
affinity for 25-hydroxy vitamin D2 of 107 to 1014
liters/mole and a binding affinity for 25-hydroxy
vitamin D3 of 10 to 106 liters/mole, wherein an
amount of the preferential binding antibody is about
1 gg/m L to about 100 pg/mL;
(b) incubating the assay medium under conditions for forming
the complexes,
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(c) determining the amount of signal from the complexes, and
(d) relating the amount of signal to the total amount of 25-
hydroxy vitamin D2 and 25-hydroxy vitamin D3 in the sample by
comparing the amount of signal to a calibrator curve.
App. Br. 13.
ISSUE AND ANALYSIS
We agree with, and adopt, the Examiner’s findings of fact and
conclusions that the appealed claims are obvious over the combined cited
prior art. We address the arguments raised by Appellants below.
Issue
Appellants argue the Examiner erred because the combined references
fail to teach the limitations of claim 15 requiring: (1) a single assay antibody
that binds both D2 and D3; and (ii) addition of a preferential binding
antibody that has a greater affinity for D2. App. Br. 5.
Analysis
The Examiner finds Laurie teaches all of the limitations of claim 15
except: (1) a single assay antibody that binds both D2 and D3; and (2)
addition of a preferential binding antibody that has a greater affinity for D2
(107 to 1014 liters/mole for D2; 10 to 106 for D3, wherein said preferential
antibody does not comprise the member of the signal producing system).
Final Act. 3—5.
The Examiner finds Hollis teaches that 25-hydroxy (“25-OH”)
vitamin D2 has less affinity for vitamin D binding protein than 25-OH
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vitamin D3. Final Act. 5 (citing Hollis 84—85). The Examiner finds
Thienpont also teaches that total 25-OH vitamin D comprises the D2 and the
D3 analytes and that it is important that measurement procedures must either
quantitate the analytes separately or together in an equimolar manner,
because some immunoassays may use antibodies with different affinities to
the D2 and D3 analytes and, therefore, might not provide an equimolar
measurement. Id. (citing Thienpont 44).
The Examiner finds that Dowd teaches a method of adjusting the
concentration of at least one analyte in a sample by adding to the assay one
or more scaling agents with a specificity to an analyte. Final Act. 5 (citing
Dowd Abstr.). The Examiner further finds that Dowd teaches the ability to
vary the sensitivity of an assay by adjusting the contribution of an analyte
with a scaling agent that is a molecule that can block the availability of a
fraction of the target by occupying the binding site. Id. (citing Dowd 1 8).
The Examiner finds Bioventix teaches availability of vitamin D-specific
sheep monoclonal antibodies, including antibodies with greater affinity for
25-OH vitamin D2, e.g., vitD2.2D10, 2D12, 4A10. Id. at 6.
The Examiner concludes that it would have been prima facie obvious
to one of ordinary skill in the art to have modified the invention for assaying
vitamin D, released from vitamin D-binding protein, as taught by Laurie,
applying a scaling agent reagent, as taught by Dowd. Final Act. 6. The
Examiner further concludes that it would have been obvious to a person of
ordinary skill that the scaling agent of Dowd could be a preferential binding
antibody (i.e., one with greater affinity for one analyte than another), such as
those as known to be available, as taught by Bioventix, in order to scale the
contribution of 25-OH D2. Id. The Examiner finds this would be logical
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because Hollis teaches that vitamin D-binding protein binds to the D3
homolog with greater affinity than it binds the D2 homolog, and, therefore,
the D2 homolog would result in a higher amount of free D2 than D3. Id.
Appellants disagree with the Examiner’s conclusion that it would
have been obvious to one of ordinary skill in the art to use the scaling agent
approach of Dowd in the assay of Laurie by adding the scaling agent to the
assay reagents. App. Br. 7. Appellants point out that the structural
differences between the D2 and D3 molecules are minimal: the side chain of
D2 contains a carbon-carbon double bond between carbons 22 and 23 and D2
has a methyl group on carbon 24, both of which are not present in D3. Id. at
7—8. Furthermore, Appellants argue, the molar mass of D2 is 396.65 grams
per mole (g/mol) and the molar mass of D3 is 384.64 g/mol. Id. at 8.
Appellants therefore contend that a person of ordinary skill would not have
had a reasonable expectation of success in using the cited Bioventix
antibody as a scaling agent, as taught by Dowd, because of the close
structural relationship of the D2 and D3 molecules that differ only by a
double bond and a methyl group. Id. Appellants acknowledge that
Bioventix teaches that one or more antibodies might show a higher
specificity for either D2 or D3 over the other, this does not mean that such an
antibody would be useful as a scaling agent to accurately measure a total
amount of D2 and D3 because of the close similarity in structure of D2 and
D3. Id.
Appellants argue further that, in the teachings of Dowd, the scaling
agent is being used for molecules that are significantly different from one
another. App. Br. 8. Appellants point to the Examples in Dowd, in which
the multi-analyte assay is carried out using five protein antigens, namely, IL-
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IB, IL-2, IL-6, IL-7 and TNFa. Id. According to Appellants, the disparate
molecular weights of these proteins, extending from 15 to 17.5 kDa are
sufficient to show the significant differences in these protein antigens. Id.
Furthermore, argue Appellants, based upon the differences in function
among the exemplary molecules, and their various amino acid sequences, a
person of skill in the art would be aware of significant differences between
them. Id.
Appellants also point to the results summarized in paragraph [0105] of
Dowd, which indicates significant differences between IL-1B, IL-2, IL-6,
IL-7 and TNFa: the anti-IL-lB antibody greatly reduced the assay response
for IL-1B while leaving the response to the other cytokines substantially
unchanged. App. Br. 8. Therefore, Appellants argue, it would not have
been obvious to a skilled artisan, relying on the teachings of Dowd, to use
the antibody taught by Bioventix, because there is a substantial difference
between the antigens taught in the Examples of Dowd whereas the D2 and
D3 homologs of Appellants’ claims exhibit minimal structural differences.
Id.
Appellants argue further that, contrary to the Examiner’s findings,
Bioventix does not refer to any of the antibodies listed as “preferentially
binding” antibodies, rather, Appellants allege, the Examiner’s language is
taken from Appellants’ Specification. App. Br. 9. Specifically, Appellants
allege that the Examiner implies that Bioventix teaches antibody vitD2.2D
10 as a “preferential binding” antibody and, thus, use of such antibody
would be considered as using a known product for its known purpose. Id.
Therefore, Appellants allege, in selectively gleaning various teachings
from the cited prior art and using the prosecution history as a guide, the
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Examiner has improperly relied upon hindsight analysis to construct a case
of prima facie obviousness and overlooks or ignores other teachings of the
cited prior art. App. Br. 10.
The Examiner responds that Appellants’ argument based on the
structural similarity of the homologs D2 and D3 is not persuasive because,
although structurally similar, the prior art at the time of the invention
recognized that vitamin D binding protein binds to one homolog with a
greater affinity than the other, and similarly taught antibodies in the prior art
that were known to preferentially bind to one homolog over the other, as
taught by Bioventix. Ans. 11—12. The Examiner therefore finds that, in
considering what was known to those of ordinary skill in the contemporary
art, and even taking into account the structural similarities of the D2 and D3
homologs, a person of ordinary skill in the art would have had a reasonable
expectation of success in applying a scaling agent, as taught by Dowd, to
compensate for the higher release of one homolog over the other upon
addition of the scaling agent. Id. at 12. Specifically, the Examiner finds
that, by applying the teachings of Dowd and employing the preferentially-
binding antibody of Bioventix as the scaling agent, a person of ordinary skill
in the art would have been motivated to modify the method of Laurie in the
expectation of achieving an equimolar assay, which Thienpont teaches is
important for accurate measure of Vitamin D in a sample. Id.
The Examiner further finds that, regardless of the structure of the
targets in the Examples taught by Dowd, Dowd teaches that it was known in
the art to use the technique of applying a scaling agent reagent with a
specificity for a target in order to adjust the concentration of at least one
analyte. Ans. 14. The Examiner finds the technique taught by
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Dowd is capable of adjusting (compensating) for the higher concentration
analyte, and that there is nothing in the teachings of Dowd that would teach
or suggest to a person of ordinary skill that the scaling agent can only be
applied to assays for multi-analytes that are significantly structurally
different. Id.
Furthermore, the Examiner finds that Bioventix teaches an antibody
that meets the definition supplied by Appellants for a “preferentially binding
antibody” and it is not the case that this supports any admission or indication
of hindsight reasoning. Ans. 14. Rather, the Examiner is merely clearly
relating the teaching to the addressed limitation of the claim, by using the
language recited in the claim. Id. at 14—15.
We are not persuaded by Appellants’ arguments. With respect to
Appellants’ argument that Laurie fails to teach “a single assay antibody that
binds both D2 and D3,” Appellants adduce no evidence in their Appeal Brief
in support of this contention. See App. Br. 3^4. A conclusory statement,
unsupported by objective evidence of record, constitutes mere attorney
argument, to which we accord little probative weight. See In re Geisler, 116
F.3d 1465, 1470 (Fed. Cir. 1997). Moreover, Laurie teaches:
[T]he present invention satisfies the pressing need for a simple
yet effective method for measuring vitamin D metabolite in a
serum or plasma sample. It is based upon the surprising
discovery of non-competitive displacement agents which enable
effective separation of vitamin D metabolites from binding
proteins to enable the amount of vitamin D metabolites to be
detected or measured, without competing with the protein or
requiring its extraction from the sample.
Laurie 119. Laurie further teaches:
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Any one or more metabolites of vitamin D may be
measured in the method of the present invention. In a preferred
embodiment, a specific vitamin D metabolite is measured in a
sample, although it is envisaged thatfor some applications it may
be preferred to measure two or more types of metabolite present.
Id. at 122 (emphasis added). We agree with the Examiner’s finding that a
person of ordinary skill would understand from these teachings of Laurie
that the displacement agents taught by Laurie, such as vitamin D binding
protein, would be capable of binding both D2 and D3 analog forms of 25-OH
vitamin D.
Appellants argue that the structural similarities between the D2 and D3
forms would deter a person of ordinary skill from using the scaling method
of Dowd combined with the selective 25-OH vitamin D-binding antibodies
of Bioventix. We are not persuaded. We acknowledge Appellants’ point
that there are significant similarities between the chemical structure of the
D2 and D3 analog forms. Nevertheless, Bioventix expressly teaches that its
antibodies are capable of selectively binding to either the D2 or D3 form of
25-OH vitamin D with high reliability. Bioventix 1. Moreover, Appellants
point to no teaching or suggestion of Dowd that states that immunologically
distinct, but structurally similar analogs cannot be used in its analysis. To
the contrary, Dowd teaches:
The term “scaling agent” as used herein is intended to
include all substances which are able to bind the analyte, either
directly (i.e., without an intermediate binding substance) or
indirectly (i.e., with one or more intermediate binding substances
forming a linkage). Preferably, the scaling agent is a specific
binding substance capable of binding directly or indirectly to the
analyte with a high affinity, typically being at least about 107 M"
\ usually being at least about 109 M"1, sometimes being 1010 M"
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\ and optimally being 1011 M'1 or 1012 M'1 or greater. The scaling
agent should be free from cross-reactivity with other substances
that may be present in the sample or in an assay reagent.
Preferably, the association between the scaling agent and
analyte, e.g., when the analyte is an antigen, is based on highly
specific noncovalent interactions between the antigenic
determinant, or epitope, of the antigen and the variable-region
domain of an antibody molecule used as the scaling agent.
Dowd 111 (emphasis added). Dowd thus teaches that the desirable quality
of a scaling agent is the specificity of the agent for the analyte. We agree
with the Examiner that a person of ordinary skill in the art would understand
that the D2-selectively binding antibodies of Bioventix exhibit the substrate
specificity taught by Dowd.
Nor are we persuaded that Bioventix fails to teach or suggest a
“preferential binding antibody,” as recited in claim 15. Appellants’
Specification discloses the definition of “preferential binding affinity” as
meaning “that the binding affinity of the non-assay antibody for the
excessive analyte homolog is greater than the binding affinity of the non­
assay antibody for the non-excessive analyte homolog.” Spec. 133.
Bioventix teaches that its vitD2.2D10, 2D 12, and 4A10 antibodies exhibit
strongly preferential binding to the D2 analog over D3. Bioventix 1. We
agree with the Examiner’s finding that a person of ordinary skill would
understand that the teachings of Bioventix correspond to Appellants’
definition of the claim term “preferential binding antibody.”
Finally, we are not persuaded that the Examiner has impermissibly
employed hindsight analysis in establishing a prima facie case of
obviousness. The test for obviousness is not:
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whether the features of a secondary reference may be bodily
incorporated into the structure of the primary reference; nor is it
that the claimed invention must be expressly suggested in any
one or all of the references. Rather, the test is what the combined
teachings of the references would have suggested to those of
ordinary skill in the art.
In re Keller, 642 F.2d 413, 425 (C.C.P.A. 1981). Furthermore:
Any judgment on obviousness is in a sense necessarily a
reconstruction based upon hindsight reasoning, but so long as it
takes into account only knowledge which was within the level of
ordinary skill at the time the claimed invention was made and
does not include knowledge gleaned only from applicant’s
disclosure, such a reconstruction is proper.
In re McLaughlin, 443 F.2d 1392, 1395 (C.C.P.A. 1971). We agree with the
Examiner that the combined references teach or suggest the limitations of
Appellants’ claims. Moreover, Appellants point to no knowledge or
teaching that could have been gleaned only from Appellants’ Specification.
We consequently affirm the Examiner’s rejection of claim 15.
Furthermore, Appellants argue claim 16 together with claim 15, and
employ the same arguments separately for claims 17—20. App. Br. 5, 11.
We consequently affirm those rejections for the same reasons we affirm the
Examiner’s rejection of claim 15.
DECISION
The Examiner’s rejection of claims 15—20 as unpatentable under 35
U.S.C. § 103(a) is affirmed.
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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).
AFFIRMED
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