Ex parte Agnello

Board of Patent Appeals and Interferences

Jul 14, 1999

07911667 (B.P.A.I. Jul. 14, 1999)

Application for patent filed July 8, 1992.1
1
THIS OPINION WAS NOT WRITTEN FOR PUBLICATION
The opinion in support of the decision being entered today (1) was not written for
publication in a law journal and (2) is not binding precedent of the Board.
Paper No. 21
UNITED STATES PATENT AND TRADEMARK OFFICE
__________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________
Ex parte VINCENT AGNELLO
__________
Appeal No. 95-4481
Application 07/911,6671
__________
ON BRIEF
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Before WINTERS, WILLIAM F. SMITH, and LORIN, Administrative Patent Judges.
WINTERS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the final rejection of claims 1 through
7, all the claims in the application.
Appeal No. 95-4481
Application No. 07/911,667
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Claims 1 through 3 are illustrative of the subject matter on appeal and read as
follows:
1. A method of assaying for antibodies to human double-stranded DNA in a liquid,
human-serum specimen, said method comprising the steps of:
forming a first incubation mixture of said specimen and a solid phase
immunoadsorbent having immobilized thereon animal anti-human IgG antibody including
F(ab')2 fragment specific for IgG Fc;
incubating said first mixture under conditions and for a period of time sufficient for
Fc in human IgG in said specimen to become bound by said F(ab')2 fragment in said
animal anti-IgG antibody;
forming a second incubation mixture of said first mixture and digoximenin-labelled
synthetic double-stranded DNA under such conditions and for a period of time sufficient to
bind to said immunoadsorbent any anti-DNA antibodies which may be present in the
serum so as to form a double-stranded DNA antibody that has substantially no single
stranded or denatured components;
detecting the amount of digoxigenin labelled synthetic double-stranded DNA bound
to said immunoadsorbent; and
relating the amount of bound labelled synthetic double-stranded DNA detected to a
predetermined quantitative relationship between the amount of labelled double-stranded
DNA and the amount of animal anti-human IgG antibody to determine the amount of human
IgG in said specimen.
2. A method of assaying for antibodies to human double-stranded DNA in a human
serum specimen, said method comprising the steps of:
capturing the anti-double-stranded DNA portion of IgG in said human serum
specimen by the Fc part of a molecule using solid phase immobilized F(ab')2 fragment of
anti-human IgG specific for Fc;
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Application No. 07/911,667
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incubating the captured IgG with synthetic double-stranded DNA tagged with a
moiety from which a signal proportional to the quantity of said synthetic double-stranded
DNA can be elicited;
eliciting said signal; and
quantifying the amount of antibody to double-stranded DNA in accordance with the
elicited signal.
3. A method as defined in claim 2 wherein said
captured IgG is incubated with synthetic double-stranded DNA tagged with alkaline
phosphatase, and said elicited signal is proportional to the quantity of alkaline
phosphatase tagging said synthetic double-stranded DNA.
The references relied on by the examiner are:
Litman et al. (Litman) 4,391,904 July 5, 1983
Denise Pollard-Knight (Pollard-Knight), "Current Methods In Nonradioactive Nucleic Acid
Labeling and Detection," 2 Technique-A Journal of Methods in Cell and Molecular Biology,
no. 3, 112-132 (June 1990).
Richard M. Pope, et al. (Pope), "IgG Rheumatoid Factor: Analysis of Various Species of
IgG for Detection by Radioimmunoassay," 97 Journal of Methods. no.6, 842-853 (1981).
Woodruff Emlen, et al. (Emlen), "A New ELISA for the Detection of Double-Stranded DNA
Antibodies," 132 Journal of Immunological Methods, 91-101 (1990).
Claims 1 and 2 stand rejected under 35 U.S.C. § 103 as unpatentable over Litman
in view of Pope and Emlen and claims 3 through 7 stand rejected under 35 U.S.C. § 103
as unpatentable over Litman in view of Pope and Emlen and further in view of Pollard-
Appeal No. 95-4481
Application No. 07/911,667
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Knight. We reverse both rejections. In addition, we raise an issue for the examiner to
consider upon return of the application.
DISCUSSION
The claims on appeal are directed to measurement of circulating human antibodies
to double stranded DNA (dsDNA). A serum sample is incubated with immobilized
antibodies or F(ab’)2 fragments specific for the Fc region of human IgG to capture and
immobilize IgG present in the sample; the captured, immobilized IgG is incubated with
labeled synthetic dsDNA, forming an immunological complex if antibodies specific for
dsDNA are present; and the amount of dsDNA-specific antibody in the sample is
determined by measuring the amount of bound labeled dsDNA. Claim 1 recites that the
dsDNA label is digoxigenin, while claim 3 recites that the label is alkaline phosphatase.
Litman discloses a generic immunoassay protocol “employing rigid solid surfaces
which may or may not be separated from the assay medium for measurement, where the
signal may be developed without concern as to the presence of reagents in the solution
affecting the observed signal on the solid surface.” IgG is listed as one of hundreds of
analytes which can be detected by Litman’s assay protocol. There is no mention of IgG of
any particular specificity. See column 1, lines 41-45 and column 17, line 67.
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Pope analyzes various species of IgG to determine “which species of IgG is the
most sensitive and specific antigen for the detection of IgG [rheumatoid factor] by
radioimmunoassay.” See page 842.
Emlen discloses an ELISA for the detection of circulating antibodies specific for
dsDNA in which biotinylated dsDNA is immobilized in streptavidin-coated wells, the
immobilized dsDNA is used to capture antibodies specific for dsDNA, and the captured
antibodies are detected with peroxidase-labeled anti-human IgG antibodies. The
reference focuses on avoiding the problems of a number of conventional assays for
detection of anti-dsDNA antibodies, most of which rely on immobilized DNA to capture
circulating antibodies, and all of which are “plagued with the problem of purity of dsDNA,
as well as problems unique to each assay.” See the Introduction section, especially the
sentence bridging pages 91 and 92. Emlen overcomes the problems associated with the
other assays by controlling the purity and antigenicity of the immobilized dsDNA.
Pollard-Knight discloses a number of non-radioactive substances used to label
nucleic acids in hybridization assays. The labeling substances include digoxigenin, biotin
and alkaline phosphatase.
The examiner believes that it would have been obvious for one of ordinary skill in
the art “to combine the solid phase immunoadsorbent for use in a reversible sandwich
immunoassay as disclosed by Litman et al., combined with a method of purifying IgG via
Appeal No. 95-4481
Application No. 07/911,667
As stated in Pro-Mold & Tool Co. v. Great Lakes Plastics, Inc., 75 F.3d 1568,2
1573, 37 USPQ2d 1626, 1629 (Fed. Cir. 1996) (citation omitted), “It is well-established
that before a conclusion of obviousness may be made based on a combination of
references, there must have been a reason, suggestion or motivation to lead an inventor to
combine those references.”
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the Fc regions as taught by Pope et al. to bind to the immunoadsorbent solid support and
immunoassays for the detection of dsDNA antibodies as taught by Emlen.” With regard to
claims 3 through 7, the examiner believes that it would have been obvious “to develop a
range of dsDNA labels used for quantitative detection.” According to the examiner, the
reason, suggestion or motivation to combine these references is “to achieve methods of
assaying for antibodies to human double-stranded DNA in a human-serum specimen as a
whole . . . for the expected advantage of diagnosis and management of patients with . . .
diseases associated with antibodies to double-stranded DNA.” See the Answer, pages 5
and 7. We disagree.2
We have no doubt that the prior art could be modified in a manner consistent with
appellant’s specification and claims. The mere fact that the prior art could be so modified,
however, would not have made the modification obvious unless the prior art suggested the
desirability of the modification. In re Gordon, 733 F.2d 900, 902, 221 USPQ 1125, 1127
(Fed. Cir. 1984). Here, we find no cogent reason stemming from the prior art which would
have led a person having ordinary skill to the claimed invention. In our judgment, the
Appeal No. 95-4481
Application No. 07/911,667
Pope’s starting material was papain-digested IgG. Papain digestion cleaves IgG3
into Fc and Fab fragments; only the Fc fragments would be retained on Pope’s anti-Fc
column. See Methods, lines 9 through 11. Also see Illustrated Dictionary of Immunology,
R.E. Lewis, CRC Press, Inc., Boca Raton, FL, 1995, “papain hydrolysis,” page 227. (Copy
enclosed).
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examiner’s proposed reason for combining references amounts to a restatement of the
objectives of appellant’s invention and does not stem from the cited prior art.
Even assuming arguendo that the combination of references were proper,
nevertheless, the combined disclosures of these references are insufficient to support the
examiner’s conclusion that the claimed method of detecting double-stranded DNA-specific
IgG would have been obvious to one of ordinary skill in the art.
Suffice it to say that Litman and Pope have little or nothing in common with the
claimed invention. At best, Litman teaches that IgG, as a class, can be detected by solid
phase immunoassay. Pope was cited to show immobilization of IgG on an anti-Fc column,
but actually shows immobilization of only the Fc portion of the antibody (which does not
exhibit antigen specificity). 3
Emlen, which discloses a solid phase assay for detection of antibodies specific for
dsDNA, would appear to be the most relevant of the references relied upon. In the last
paragraph of the Answer, after addressing appellant’s arguments, the examiner contends
that the claimed invention is simply the Emlen assay with the order of binding reversed. In
our view, this is the strongest argument presented in support of the examiner’s conclusion
Appeal No. 95-4481
Application No. 07/911,667
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of obviousness. However, it is factually inaccurate. Merely reversing the order of binding
in Emlen’s assay would leave a number of differences between the two assays
unaddressed, e.g., differences in specific reagents. Even if Emlen did describe the
present assay in reverse order, on this record, the examiner has provided no reason,
suggestion or motivation stemming from the prior art to disassemble Emlen’s assay and
reassemble it in reverse order.
In conclusion, we agree with appellant that the examiner did not meet the initial
burden of establishing a prima facie case of obviousness of claims 1 through 7.
Accordingly, the rejection of claims 1 through 7 under 35 U.S.C. § 103 is reversed.
OTHER ISSUE
Claims 1 through 7 are now free of rejection. However, we note that the claims are
confusing in a number of respects. Merely by way of example, the third step of claim 1
recites that the first mixture (i.e., captured human IgG, immobilized on the
immunoadsorbent of the first step) is incubated with dsDNA “for a period of time sufficient
to bind to said immunoadsorbent any anti-DNA antibodies which may be present in the
serum.” This is confusing because the anti-dsDNA antibodies are already on the
immunoadsorbent at this point in the assay; it is the dsDNA that is captured in the third
step. Also, the last step of claim 1 is inconsistent with the preamble; the method does not
determine the amount of IgG in the sample, it determines only that portion of the population
Appeal No. 95-4481
Application No. 07/911,667
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specific for dsDNA. On return of this application to the Examining Corps, we recommend
that both appellant and the examiner take steps to clarify the language of the claims.
The decision of the examiner is reversed.
No time period for taking any subsequent action in connection with this appeal
may be extended under 37 C.F.R. § 1.136(a).
REVERSED
)
SHERMAN D. WINTERS )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
WILLIAM F. SMITH )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
HUBERT C. LORIN )
Administrative Patent Judge )
SDW/dal
ROBERT J. SCHILLER
LAPPIN & KUSMER
TWO HUNDRED STATE STREET
Appeal No. 95-4481
Application No. 07/911,667
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BOSTON, MASS. 02109