Ex Parte Rutanen

Board of Patent Appeals and Interferences

Aug 4, 2009

11048685 (B.P.A.I. Aug. 4, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte EEVA-MARJA RUTANEN
__________

Appeal 2009-001910
Application 11/048,685
Technology Center 1600
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Decided: August 4, 2009
__________

Before DEMETRA J. MILLS, ERIC GRIMES, and RICHARD M.
LEBOVITZ, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

STATEMENT OF CASE
This is an appeal under 35 U.S.C. § 134. We have jurisdiction under
35 U.S.C. § 6(b).
The following claim is representative.
1. A method for identifying a patient with intact foetal membranes
possessing risk factors indicative of preterm delivery comprising:

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a) detecting a level of IGFBP-1 in an essentially blood-free vaginal or
cervical secretion sample from said patient with an antibody that recognizes
IGFBP-1;
b) comparing said level of IGFBP-1 to a high level of 100 µg/l and a low
level of less than 1.0 µg/l;
c) identifying a level of IGFBP-1 that is less than 100 µg/l and equal to or
greater than 1 µg/l; and
d) providing medical advice designed to prevent preterm delivery to said
patient where said sample has an IGFBP-1 level that is less than 100 µg/l
and equal to or greater than 1 µg/l, wherein said level of IGFBP-1 being less
than 100 µg/l and equal to or greater than 1 µg/l, despite intact foetal
membranes, indicates that said patient possesses risk factors indicative of
preterm delivery, said risk factor of said patient being increased as compared
to patients with an IGFBP-1 level of less than 1 µg/µl [sic].

CITED REFERENCES
Senyei US 5,096,830 Mar. 17, 1992
Konstantinov US 5,597,700 Jan. 28, 1997

Rutanen WO 92/12426 July 23, 1992
Rutanen’99 WO 99/58974 Nov. 18, 1999

Eeva-Marja Rutanen et al., “Diagnosis Of Premature Rupture Of Fetal
Membranes By The Measurment Of Insulin-Like Growth Factor Binding
Protein-1 In Cervical Secretion,” Department of Obstetrics and Gynecology,
University Central Hospital, and Minerva Institute for Medical Research, 38,
Helsinki Finland.

Charles J. Lockwood et al., “Fetal Fibronectin In Cervical And Vaginal
Secretions As A Predictor Of Preterm Delivery,” 325 (10) The New England
Journal of Medicine 669-674 (1991).

Eeva-Marja Rutanen et al., “Measurement of insulin-like growth factor
binding protein-1 in cervical/vaginal secretions: comparison with the ROM-
check Membrane Immunoassay in the diagnosis of ruptured fetal
membranes,” 214 Clinica Chimica Acta 73-81 (1993).

Melissa Westwood et al., “The Phosphorylation Pattern of Insulin-Like
Growth Factor-Binding Protein-1 in Normal Plasma Is Different from That
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in Amniotic Fluid and Changes during Pregnancy,” 79 (6) Journal of
Clinical Endocrinology and Metabolism, 1735-1741 (1994).

Charles J. Lockwood, MD. et al. “Fetal membrane rupture is associated with
the presence of insulin-like growth factor-binding protein-1 in vaginal
secretions,” 171 (1) Am. J. Obstet. Gynecol. 146-149 (July 1994).

Eeva-Marja Rutanen et al., “Evaluation of a rapid strip test for insulin-like
growth factor binding protein-1 in the diagnosis of ruptured fetal
membranes,” 253 Clinica Chimica Acta, 91-101 (1996).

GROUNDS OF REJECTION
1. Claims 1, 3-6, 13, 15-18, 25, and 26 are rejected under 35 U.S.C. §
112, first paragraph for lack of written description.
2. Claims 1, 3-7, 9-13, 15-19, and 21-26 are rejected under 35 U.S.C.
§ 112, first paragraph for lack of enablement.
3. Claims 1, 3-7, 9-13, 15-19, and 21-26 are rejected under 35 U.S.C.
§ 112, second paragraph for claim indefiniteness.
4. Claims 26 is rejected under 35 U.S.C. § 102(b) over Rutanen 1991.
5. Claims 1, 3-7, 9-12, 19, and 21-26 are rejected under 35 U.S.C. §
103(a) as being unpatentable over Rutanen (1991) in view of Senyei.

Written Description
1. Claims 1, 3-6, 13, 15-18, 25, and 26 are rejected under 35 U.S.C. §
112, first paragraph for lack of written description.

ISSUE
The Examiner finds that there is
no written description or support for the invention as is now
claimed wherein those patients determined to have
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"intermediate" levels of insulin-like growth factor binding
protein 1 (IGFBP- 1) above baseline and below that indicative
of membrane rupture, that is those patients alleged to have a
mature cervix, are advised or treated to prevent pre-term
delivery because the [S]pecification teaches against an
expectation of success in treating such patients (i.e.
considerable changes have already taken place in the cervix and
delivery is impending).
(Ans. 7.)
Appellant contends that there is written descriptive support in the
Specification, referencing specific locations in the Specification, for the
Appellant’s claimed invention. (App. Br. 11-17.)
The Issue is: Has Appellant demonstrated error in the Examiner’s
finding that the Specification does not describe advising patients to prevent
pre-term delivery?

PRINCIPLES OF LAW
“The ‘written description’ requirement . . . serves both to satisfy the
inventor’s obligation to disclose the technologic knowledge upon which the
patent is based, and to demonstrate that the patentee was in possession of the
invention that is claimed. . . . The descriptive text needed to meet these
requirements varies with the nature and scope of the invention at issue, and
with the scientific and technologic knowledge already in existence.” Capon
v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). “It is not necessary that
every permutation within a generally operable invention be effective in order
for an inventor to obtain a generic claim, provided that the effect is
sufficiently demonstrated to characterize a generic invention.” Id. at 1359.

FINDINGS OF FACT
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1. According to the inventor's observations, the concentration of
IGFBP-1 in vaginal or cervical secretions can be elevated even when
the foetal membranes are intact. However, in a sample extracted in 0.5
ml of a buffer, the IGFBP-1 concentration does not exceed about 100
µg/l, unless it originates from amniotic fluid resulting from ruptured
foetal membranes. This finding has brought to light the fact that, when
the foetal membranes remain intact, this slight but higher than
baseline elevation can be interpreted as protein leaking directly from
decidual cells. If the sample contains amniotic fluid, the test based on
the invention cannot be used to show elevation of the IGFBP-1 level
due to leaking decidual cells, since the concentration of IGFBP-1 due
to the presence of amniotic fluid is higher.

(Spec. 12.)

2. “Table 3 shows that, as spontaneous delivery approached in
women whose membranes were still intact, the concentration of IGFBP-1 in
the extracted sample varied between about 1 and 61 µg/l. Higher
concentrations of IGFBP-1 (8100, 6160 µ/l [sic, µg/l]) associated with
ruptured foetal membranes are clearly distinguishable.” (Spec. 15.)
3. The Specification states that, “[c]oncentrations [of IGFBP-1]
above the baseline level indicate the presence of some active process. This,
together with clinical information, is used to decide whether any treatment is
necessary.” (Id.)
4. The Declaration of Mika Nuutila testifies to the use of Dr.
Rutanen’s invention in the course of practicing medicine and that “Dr.
Rutanen’s invention has provided useful results in the diagnosis and
treatment of pregnant women at risk of preterm delivery.” (Declaration,
page 2.)
5. Appellant relies on the Declaration of Jorma Paavonen explaining
that one of ordinary skill in the art reading the Specification would
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understand that it explains the invention now claimed. (Br. 17; Declaration
Paavonen, pages 2-4.)

ANALYSIS
The Examiner finds that there is no written description or support for
the invention as is now claimed because the Specification teaches against an
expectation of success in treating patients with intermediate levels of
IGFBP-1 and at risk of preterm delivery as claimed because “considerable
changes have already taken place in the cervix and delivery is impending.”
(Ans. 7.)
We are not persuaded by the Examiner’s finding. Appellant claims a
method for identifying a patient with intact foetal membranes possessing
risk factors indicative of preterm delivery. The claim does not require
prevention of preterm delivery as alleged by the Examiner. The claim
requires in step (d), “providing medical advice designed to prevent preterm
delivery.” Thus, no particular expectation of success of prevention of
preterm delivery is required by the claim as argued by the Examiner.
It would reasonably appear from the facts of record (FF1-5) that the
Specification describes the method as claimed.

CONCLUSION OF LAW
Appellant has demonstrated error in the Examiner’s finding that the
Specification does not describe advising patients to prevent pre-term
delivery. The written description rejection is reversed.

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Enablement
2. Claims 1, 3-7, 9-13, 15-19, and 21-26 are rejected under 35 U.S.C.
§ 112, first paragraph for lack of enablement.

ISSUE
The Examiner argues that the Specification is not enabling for
a method of determination of insulin-like growth factor binding
protein 1 (IGFBP- 1) as indicative of susceptibility to preterm
or impending delivery, and/or maturity of the cervix, or risk of
preterm labor, or for any indication other than the known
indication of fetal membrane rupture. There is nothing in
evidence which would allow one to determine cervical ripeness
(i.e. maturity) or other delivery indications, and to exclude the
presence of amniotic fluid, on the basis of the disclosed and
instantly claimed methods alone.
(Ans. 8.)
The Examiner argues that “Appellant has provided no nexus
believable to one of skill in the art between ‘intermediate’ levels of IGFBP-1
(i.e. instantly disclosed and claimed as less than the 100 µg/l level selected,
in order to limit the detection of false positives (page 12; see also Rutanen et
al., 1993), as indicative of fetal membrane rupture.” (Answer 9.) The
Examiner argues that “the source and significance of the instant
‘intermediate’ levels of detectable IGFBP-1 in cervical or vaginal secretions
(also referred to herein as cervicovaginal secretions) would seem to be
unknown and unpredictable for a variety of reasons, particularly in 1992.”
(Id.)
The issue is: Has Appellant demonstrated that the Examiner erred in
concluding that the Specification is not enabling to practice the claimed
invention?
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PRINCIPLES OF LAW
As explained in In re Brana, 51 F.3d 1560, 1567 (Fed. Cir. 1995), the
USPTO should not confuse "the requirements under the law for obtaining a
patent with the requirements for obtaining government approval to market a
particular drug for human consumption," citing Scott v. Finney, 34 F.3d
1058, 1063 (Fed. Cir. 1994). See In re Anthony, 414 F.2d 1383, 1395
(CCPA 1969)("Congress has given the responsibility to the FDA[1 ], not to
the [PTO], to determine . . . whether drugs are sufficiently safe"). This logic
would similarly apply to diagnostic medical devices.
Patentability determinations are based on a preponderance of the
evidence. “After evidence or argument is submitted by the applicant in
response, patentability is determined on the totality of the record, by a
preponderance of the evidence with due consideration to persuasiveness of
argument.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).

FINDINGS OF FACT
6. The Specification page 15, Table 3, evidences that there is a
population of pregnant women patients with intact and unruptured foetal
membranes with a level of IGFBP-1 that is less than 100 µg/l and equal

1 The Federal Food, Drug, and Cosmetic Act (FD&C Act) gives FDA broad
authority to regulate medical devices, which are defined in part as any “in
vitro reagent or other related article, including any component, part, or
accessory, which is . . . intended for use in the diagnosis of disease.” 21
U.S.C. § 321(h) (2005).
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to or greater than 1 µg/l, that is at risk of preterm delivery and may
require medical advice different from a patient having preterm
contractions but an IGFBP-1 level that is less than 1 µg/l.
7. According to the Specification, page 3, some 80 to 90% of patients
having preterm contractions, require no intervention, however from 10-
20% of pregnant women having preterm contractions require some form
of medical advice or intervention to delay or prevent preterm delivery.
8. Lockwood 1994 suggests that a level of IGFBP-1 of greater than 3
µg/l is indicative of foetal membrane rupture (Ans. 13)
9. Rutanen 1996 mentions IGFBP-1 levels of 25 µg/l is indicative of
foetal membrane rupture. (Ans. 13.)

ANALYSIS
We are not persuaded by the Examiner’s reasoning. The Specification
page 15, Table 3, evidences that there is a population of pregnant women
patients with intact and unruptured foetal membranes with a level of IGFBP-
1 that is less than 100 µg/l and equal to or greater than 1 µg/l, that is at risk
of preterm delivery and may require medical advice different from a patient
having preterm contractions but an IGFBP-1 level that is less than 1 µg/l.
According to the Specification, page 3, some 80 to 90% of patients having
preterm contractions require no intervention, however from 10-20% of
pregnant women having preterm contractions require some form of medical
advice or intervention to delay or prevent preterm delivery. Dr. Mika
Nuutila, a physician, testifies that the claimed diagnostic testing is effective.
(FF 4.)
While we acknowledge that Lockwood 1994 suggests that a level of
IGFBP-1 of greater than 3 µg/l is indicative of foetal membrane rupture
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(Ans. 13) and Rutanen 1996 mentions IGFBP-1 levels of 25 µg/l is
indicative of foetal membrane rupture, the claimed method as defined in its
preamble involves those patients with the claimed IGFBP-1 level whose
membranes are not ruptured. The weight of the evidence supports the
position of Appellant, and the enablement rejection is reversed.

CONCLUSION OF LAW
Appellant has demonstrated that the Examiner erred in concluding
that the Specification is not enabling to practice the claimed invention.

Indefiniteness
Claims 1, 3-7, 9-13, 15-19, and 21-26
Claims 1, 3-7, 9-13, 15-19, and 21-26 are rejected under 35 U.S.C. §
112, second paragraph for claim indefiniteness.
The Examiner argues that the claimed method steps are unclear
because there is no connection between the sample level in step (a) and the
identified level in step (c). (Ans. 15.)
PRINCIPLES OF LAW
“The test for definiteness is whether one skilled in the art would
understand the bounds of the claim when read in light of the specification.”
Miles Laboratories, Inc. v. Shandon, Inc., 997 F.2d 870, 875 (Fed. Cir.
1993). Claims are in compliance with 35 U.S.C. § 112, second paragraph, if
“the claims, read in light of the [S]pecification, reasonably apprise those
skilled in the art both of the utilization and scope of the invention, and if the
language is as precise as the subject matter permits.” Hybritech, Inc. v.
Monoclonal Antibodies, Inc., 802 F.2d 1367, 1385 (Fed. Cir. 1986).

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ANALYSIS
We conclude that one skilled in the art would understand the bounds
of the claim when read in light of the Specification. In our view, one of
ordinary skill in the art reading the claimed method would understand that a
level of IGFBP-1 in an essentially blood-free vaginal or cervical secretion
sample is detected and that value is compared to a level of IGFBP-1 to a
high level of 100 µg/l and a low level of less than 1.0 µg/l. If the detection
identifies a level of IGFBP-1 that is less than 100 µg/l and equal to or
greater than 1 µg/l then medical advice is given. The indefiniteness
rejection of claims 1, 3-7, 9-13, 15-19, and 21-26 is reversed.

Claims 13 and 15-18
The Examiner concludes that claims 13 and 15-18 are unclear as to
what is intended by the phrase “intact maturation of the lower.” (Ans. 15.)
Appellant acknowledges that the term “membranes” was inadvertently
deleted from claim 13. (App. Br. 22.) Therefore, we affirm the rejection of
claims 13 and 15-18.

Anticipation
Claims 26 is rejected under 35 U.S.C. § 102(b) over Rutanen 1991.
ISSUE
The Examiner finds that:
With sandwich immunoassays using two monoclonal antibodies, one
of which being implicitly labeled, Rutanen et al. detected levels of
IGFBP-1 in swabbed samples of cervical secretions in various ranges:
undetectable in nonpregnant patients; a range of from undetectable to
detectable up to 90 ng/ml (i.e. 90 µg/l) in pregnant patients with
apparently intact fetal membranes; and an increased level ranging
from 175 to 20,000 ng/ml (i.e. µg/l) in pregnant patients implicitly
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highly susceptible to delivery due to rupture of fetal membranes.
Rutanen et al. implicitly teach comparisons among detected ranges of
IGFBP-1 levels, pregnancy status, and fetal membrane status,
implicitly identifying the samples in each range. … Providing medical
advice to a patient regarding the ranges of detected IGFBP-1 levels,
pregnancy status, fetal membrane status, and a safe, full-term,
delivery would have been implicit in the medical care of pregnant
patients.

(Ans. 16.)

Appellant contends that
[b]ecause Rutanen et al. (1991) publication teaches only a binary,
high-low IGFBP-1 concentration level in cervical samples taken from
pregnant women for diagnosing ruptured foetal membranes, it fails to
expressly anticipate the presently claimed method for detecting an
intermediate IGFBP-1 concentration range in vaginal/cervical samples
for diagnosing a risk for pre-term delivery recited in claim 26.
Because, in view of the teachings of Rutanen et al. (1991), there is no
necessity that intermediate IGFBP-1 concentrations be correlated with
a detached state of foetal membranes indicative of a risk for pre-term
delivery, the Rutanen et al. (1991) publication cannot inherently
anticipate the present claims.

(App. Br. 25.)

The issue is: Has Appellant demonstrated error in the Examiner’s
anticipation rejection?

FACT AND ANALYSIS
We find Appellant’s arguments convincing. Rutanen 1991 does not
specifically attribute any significance to the claimed values of IGFBP-1 in a
patient with intact foetal membranes and a risk of preterm delivery, and
therefore does not teach the claimed step of “d) providing medical advice
designed to prevent preterm delivery to said patient where said sample has
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an IGFBP-1 level that is less than 100 µg/l and equal to or greater than 1
µg/l.”

CONCLUSION OF LAW
Appellant has demonstrated error in the Examiner’s anticipation
rejection.

OBVIOUSNESS
Claims 1, 3-7, 9-12, 19, and 21-26 are rejected under 35 U.S.C. §
103(a) as being unpatentable over Rutanen (1991) in view of Senyei.

ISSUE
According to the Examiner the “teachings of Rutanen et al. (1991)
differ from the invention as instantly disclosed and/or claimed in not
teaching extraction of the sample from the swab and in not teaching the
ranges of IGFBP-1 levels as instantly claimed.” (Ans. 18.)
The Examiner concludes that it “would have been obvious to one of
ordinary skill in the art at the time the instant invention was made to have
extracted a cervicovaginal secretion sample from the swab used for its
collection prior to performance of the immunoassay of Rutanen et al. (1991)
because Senyei et al. teach that this step is conventional.” (Ans. 18.)
We do not find that Senyei overcomes the deficiencies of Rutanen
1991 as discussed above, and the rejection of the claims for obviousness is
reversed.

SUMMARY
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All rejections are reversed except for the rejection of claims 13 and
15-18 for claim indefiniteness, which is affirmed.
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 IN PART
REVERSED IN PART

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BIRCH, STEWART, KOLASCH & BIRCH
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