Ex Parte Krieger

Board of Patent Appeals and Interferences

Sep 25, 2007

09148012 (B.P.A.I. Sep. 25, 2007)

The opinion in support of the decision being entered today
is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MONTY KRIEGER
__________

Appeal 2007-4148
Application 09/148,012
Technology Center 1600
__________

Decided: September 25, 2007
__________

Before TONI R. SCHEINER, DONALD E. ADAMS, and ERIC GRIMES,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of inhibiting pregnancy or treating steroid-related diseases. The Examiner
has rejected the claims as nonenabled and lacking an adequate description in
the Specification. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
BACKGROUND
“Scavenger receptors mediate the endocytosis of chemically modified
lipoproteins, such as acetylated LDL (AcLDL)” (Specification 2). “Hamster
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Application 09/148,012

and murine homologs of SR-BI, an AcLDL and LDL binding scavenger
receptor . . . ha[ve] been isolated and characterized” (id. at 5).
“Direct binding studies show that SR-BI expressed in mammalian
cells . . . binds HDL, without cellular degradation of the HDL-apoprotein,
and lipid is accumulated within cells expressing the receptor” (id. at 6).
SR-BI . . . mediates the uptake and transport of cholesteryl ester
from high density lipoproteins. It has been demonstrated that
transgenic animals which do not produce SR-BI are healthy,
with the exception that the females are infertile. This provides
evidence that inhibition of uptake, binding or transport of
cholesteryl ester to SR-BI can be used to inhibit pregnancy.
The same pathway can also be used to decrease production of
steroids, and therefore be used as a therapy for disorders
involving steroidal overproduction.
(Id. at 7.)
DISCUSSION
1. CLAIMS
Claims 1-9, 12, 15, 16, and 20-22 are on appeal. Claim 19 is also
pending but has been withdrawn from consideration by the Examiner.
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). We will focus on claim 1, the
broadest claim on appeal. Claim 1 reads as follows:
1. A method for inhibiting pregnancy or decreasing production of
steroids in a mammal comprising
administering a compound inhibiting uptake, binding or
transport of cholesteryl ester by SR-BI in the mammal in an amount
effective to inhibit pregnancy or to decrease production of steroids in
disorders involving steroidal overproduction.

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2. WRITTEN DESCRIPTION
Claims 1-9, 12, 15, 16, and 20-22 stand rejected under 35 U.S.C.
§ 112, first paragraph, on the basis that the
claims a[re] drawn to methods which potentially use a universe
of compounds. However, Appellant has only provided written
description of a small number of specific compounds which act
via SR-BI, including estrogen (Example 3 on pages 39-40 of
the specification), adenoviral vector encoding SR-BI (Example
5 on pages 40-45 of the specification), and anti-SR-BI antibody
(Example 8 on pages 55-66 of the specification) to alter
cholesterol levels.
(Answer 3.) The Examiner finds that the Specification does not provide an
adequate written description of the claimed method (id. at 2-3).
We agree with the Examiner that the Specification does not
adequately describe the claimed method. Describing a claim to a method
requires describing the compounds used in the method. See University of
Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004). Here,
claim 1 requires use of a compound that inhibits uptake, binding, or
transport of cholesteryl ester by SR-BI. The Specification therefore must
adequately describe that genus of compounds.
A chemical genus can be described by structural description of a
representative number of the species within the genus or by describing
“structural features common to the members of the genus, which features
constitute a substantial portion of the genus.” University of California v. Eli
Lilly and Co., 119 F.3d 1559, 1569 (Fed. Cir. 1997). The structural
description does not necessarily require disclosure of the compound’s
complete chemical structure:
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[T]he written description requirement can be met by “show[ing]
that an invention is complete by disclosure of sufficiently
detailed, relevant identifying characteristics . . . i.e., complete or
partial structure, other physical and/or chemical properties,
functional characteristics when coupled with a known or
disclosed correlation between function and structure, or some
combination of such characteristics.”
Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964, (Fed. Cir. 2002)
(emphasis omitted, bracketed material in original).
Here, claim 1 is directed to a method comprising administering a
compound that inhibits uptake, binding, or transport of cholesteryl ester by
SR-BI in order to inhibit pregnancy or decrease steroid production.
The Specification states that such inhibitors
include nucleotide molecules such as antisense
oligonucleotides, ribozymes, and triplex forming
oligonucleotides which bind to the SR-BI gene, either the
protein encoding region of the gene or the regulatory regions of
the gene; small organic molecules which bind to the SR-BI
protein; soluble SR-BI protein or fragments thereof which
competitively bind to the substrate for cell bound SR-BI; and
compounds which block binding of HDL to SR-BI.
(Specification 11.)
The Specification also describes several assays that are said to be
useful “to screen for compounds which are effective in methods for
alter[ing] SR-BI expression, concentration, or transport of cholesterol” (id.
at 14: 21-23; the assays are described on pages 14-17). The Specification
also describes in general terms how to randomly generate “receptor or
receptor encoding sequence binding molecules (id. at 18-19), computer
assisted drug design (id. at 19-20), generation of “nucleic acid regulators”
such as antisense RNA and triplex-forming oligonucleotides (id. at 20-24),
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and preparation of receptor protein fragments (id. at 24-25). Finally, the
Specification describes a working example in which antibodies to “mSR-BI”
(murine SR-BI; id. at 40: 26) were raised and combined in vitro with
SR-BI-expressing adrenocortical cells to determine the effect of the antibody
on HDL uptake and steroid production (id. at 55-66).
Thus, the Specification does not describe any structural features that
are shared by compounds having the function of “inhibiting uptake, binding
or transport of cholesteryl ester by SR-BI.” The Specification describes two
polyclonal antibody preparations that contain antibodies to murine SR-BI.
The Specification discloses the amino acid sequence of murine SR-BI (SEQ
ID NO: 4), and therefore the disclosed antibodies are adequately described.
See Noelle v. Lederman, 355 F.3d 1343, 1349 (Fed. Cir. 2004).
However, the Specification describes no other specific compounds
having the function of “inhibiting uptake, binding or transport of cholesteryl
ester by SR-BI.” The present case is therefore analogous to Rochester. In
that case, the patent claimed a method of selectively inhibiting the enzyme
PGHS-2 (also known as COX-2) by “administering a non-steroidal
compound that selectively inhibits activity of the PGHS-2 gene product to a
human.” 358 F.3d at 918. The patent “described in detail how to make cells
that express either COX-1 or COX-2, but not both . . . , as well as ‘assays for
screening compounds, including peptides, polynucleotides, and small
organic molecules to identify those that inhibit the expression or activity of
the PGHS-2 gene product.[’]” Id. at 927.
The court held that the disclosure of screening assays and general
classes of compounds was not adequate to describe compounds having the
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desired activity: without disclosure of which peptides, polynucleotides, or
small organic molecules have the desired characteristic, the claims were not
adequately described. See id. (“As pointed out by the district court,
however, the ‘850 patent does not disclose just ‘which “peptides,
polynucleotides, and small organic molecules” have the desired
characteristic of selectively inhibiting PGHS-2.’ . . . Without such
disclosure, the claimed methods cannot be said to have been described.”).
Just as in Rochester, the present application discloses several genera
of chemical compounds (“nucleotide molecules such as antisense
oligonucleotides, ribozymes, and triplex forming oligonucleotides . . . ; small
organic molecules . . . ; soluble SR-BI protein or fragments thereof . . . ; and
compounds which block binding of HDL to SR-BI”) and assays for
screening such compounds to identify those having the desired activity.
And, just as in Rochester, the present Specification does not disclose which
of the many candidate compounds have one of the recited activities. The
Rochester court held that such a disclosure does not adequately describe a
genus of compounds required to practice a claimed method.
Granted, the present case differs from Rochester in that the present
Specification describes antibodies to murine SR-BI, one of the compounds
having the activity recited in claim 1. That disclosure, however, does not
adequately distinguish the instant case from Rochester, because Appellant
has not shown that the antibody is representative of the entire genus of
compounds having the recited activities or that it shares “structural features
common to the members of the genus, which features constitute a substantial
portion of the genus.” Cf. Eli Lilly, 119 F.3d at 1569.
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Appellant argues that, in addition to antibodies that bind murine
SR-BI, the Specification describes adenoviral vectors that encode SR-BI and
transgenic animals made by inactivating SR-BI in embryonic stem cells (Br.
8-9).
These disclosures do not contribute to the description of the claimed
method. Adenoviral vectors encoding SR-BI result in overexpression of
SR-BI, the opposite effect from that required by claim 1. (Specification 40:
26-29 (mice infected with an SR-BI-encoding adenovirus transiently
overexpress SR-BI).) Inactivating the SR-BI gene in transgenic animals
results in “inhibiting uptake, binding or transport of cholesteryl ester by
SR-BI,” but Appellant has not begun to explain how this method could be
practiced on a living, mammalian patient – as required by claim 1 – who can
hardly be generated from embryonic stem cells.
Appellant also argues that “the many compounds that already exist for
regulating cholesterol levels . . . can be used to inhibit pregnancy or decrease
steroidal overproduction via the modulation of SR-BI expression or activity”
(Br. 9). Appellant argues that a “different degree of description is required
where compounds are known and one only needs to provide the criteria for
their selection and use – a degree clearly met by appellant” (id. at 10).
We do not find this argument persuasive. The record provides no
basis to expect that compounds that lower plasma cholesterol levels would
inhibit SR-BI activity, since elimination of SR-BI activity results in elevated
plasma cholesterol. (Specification 50:10-13.) Those skilled in the art would
therefore expect that inhibition of SR-BI activity by an administered
compound would also result in elevated plasma cholesterol levels.
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In addition, even though inhibiting SR-BI was shown to increase
plasma cholesterol levels in transgenic mice, it does not follow that
increasing cholesterol level in a patient having normal SR-BI function will
inhibit SR-BI, and thereby inhibit pregnancy. Appellant has pointed to no
evidence in the record that would show that SR-BI is down-regulated or
inactivated in response to elevated cholesterol levels. Thus, the evidence of
record does not support Appellant’s apparent position that any compound
that elevates cholesterol will inhibit SR-BI.
We affirm the rejection of claim 1 under 35 U.S.C. § 112, first
paragraph, for lack of adequate written description. Claims 2-9, 12, 15, 16,
and 20-22 fall with claim 1.
4. ENABLEMENT
Claims 1-9, 15, 16, and 20-22 stand rejected under 35 U.S.C. § 112,
first paragraph, on the basis that the Specification “does not reasonably
provide enablement for any method of decreasing production of steroids or
inhibiting pregnancy in a mammal” (Answer 3).1 The Examiner reasons that
Appellant has provided no guidance and working examples of
any compounds which act via SR-BI to alter pregnancy other
than those in knockout infertile female mice. In fact, the
specification, estrogen . . . , adenoviral vector encoding SR-BI
. . . , and anti-SR-BI antibody . . . have only been shown to

1 Claim 12 was also subject to this ground of rejection in the Office action
mailed August 15, 2005 but was not included in the statement of rejection in
the Examiner’s Answer. At the same time, the Examiner did not expressly
indicate that the rejection had been withdrawn with respect to claim 12. If
this application is subject to further prosecution, the Examiner should
consider whether claim 12 should be rejected for nonenablement.
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affect SR-BI and to alter cholesterol and lipoprotein levels, but
have not been shown to inhibit pregnancy in a mammal.
(Answer 4.) The Examiner also finds that the exemplified “method of
knocking out a gene in an embryonic stem cell is not comparable to a
method of altering fertility . . . in a developed mammal” (id.).
The Examiner concludes that, because of the paucity of guidance and
working examples, and the “lack of predictability as to which compounds
affecting steroid levels will inhibit pregnancy, . . . undue experimentation is
necessary to practice the claimed invention” (id. at 5).
We agree with the Examiner that the Specification does not provide
sufficient guidance to enable practice of the full scope of the claimed
method without undue experimentation. The Specification discloses that
transgenic mice that do not express SR-BI at all are infertile; the
Specification discloses no other examples of inhibiting pregnancy by
inhibiting SR-BI. The Specification provides no guidance regarding what
level of SR-BI expression above zero is sufficient to inhibit pregnancy.
The Specification provides no guidance or working examples that
would enable those skilled in the art to achieve 100% inhibition of SR-BI in
a developed animal expressing SR-BI. The Specification’s example
showing in vitro inhibition of SR-BI activity describes using SR-BI-binding
antibodies to achieve up to 85% inhibition of HDL uptake (Specification 62:
26-28), up to 70% inhibition of HDL-selective cholesteryl ester uptake (id.
at 63: 26-28), and up to 50% inhibition of cell association with HDL (id. at
64: 12-14), and up to 78% inhibition of steroid production (id. at 65: 21-23)
in murine adrenocortical cells. The record provides an inadequate basis on
which to extrapolate these in vitro results to what could be achieved in vivo,
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and does not indicate whether this level of inhibition would inhibit
pregnancy if achieved in a mammalian subject.
Thus, while the Specification provides a working example describing
inhibition of SR-BI activity in vitro, it provides no working example of the
method defined by claim 1: inhibiting pregnancy or decreasing production
of steroids in a mammalian subject in vivo. The Specification also provides
inadequate guidance regarding what level of SR-BI inhibition is required to
inhibit pregnancy and what compounds can be administered to achieve the
required inhibition.
“Patent protection is granted in return for an enabling disclosure of an
invention, not for vague intimations of general ideas that may or may not be
workable. . . . Tossing out the mere germ of an idea does not constitute
enabling disclosure. While every aspect of a generic claim certainly need
not have been carried out by an inventor, or exemplified in the specification,
reasonable detail must be provided in order to enable members of the public
to understand and carry out the invention.” Genentech Inc. v. Novo Nordisk
A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997).
While the Specification does disclose a possible connection between
female fertility and SR-BI, it does not provide adequate guidance to enable
those skilled in the art to inhibit pregnancy by inhibiting SR-BI activity
without undue experimentation. We therefore agree with the Examiner that
the Specification does not provide an enabling disclosure in compliance with
35 U.S.C. § 112, first paragraph.
Appellant argues that the working examples in the Specification
support the instant claims, and that the Miettinen paper “showing restoration
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of fertility by administration of a cholesterol lowering drug, probucal, . . .
provides further support for the claimed method.” (Br. 13.)
We do not agree that the Specification’s examples or the Miettinen
paper2 provide an enabling disclosure. The Specification’s examples show
only that an SR-BI-binding antibody can inhibit some of the activity of
SR-BI in cells in vitro; they do not show that that level of inhibition inhibits
pregnancy or even that it can be achieved in a mammalian subject. None of
the other examples substantively contribute to the enablement of the method
defined by claim 1.
The Miettinen paper does not supply the enabling guidance missing
from the Specification. First, Miettinen was published after the effective
filing date of the present application and therefore can be relied on only to
confirm assertions made in the Specification. See In re Glass, 492 F.2d
1228, 1232 (CCPA 1974) (“[A]pplication sufficiency under § 112, first
paragraph, must be judged as of its filing date. It is an applicant’s obligation
to supply enabling disclosure without reliance on what others may publish
after he has filed an application on what is supposed to be a completed
invention. If he cannot supply enabling information, he is not yet in a
position to file.” (emphasis in original)). The Specification does not assert
that drugs that affect plasma cholesterol levels, without affecting SR-BI
activity, can inhibit pregnancy. In addition, as discussed above, Appellant
has pointed to no evidence in the record that would show that cholesterol-

2 Miettinen et al., “Abnormal lipoprotein metabolism and reversible female
infertility in HDL receptor (SR-BI)-deficient mice,” Journal of Clinical
Investigation, Vol. 108, pp. 1717-1722 (2001).
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lowering or cholesterol-raising drugs affect the expression or activity of
SR-BI.
Appellant also argues that “one of skill in the art would understand
from the specification which compounds to use, and how to derive
appropriate doses with minimal routine experimentation to practice the
claimed method and inhibit fertility or treat a disorder characterized by
excessive steroidal production.” (Br. 13.)
Appellant provides no further explanation of the basis for this
assertion. For the reasons discussed above, we disagree that the
Specification provides adequate guidance to enable practice of the full scope
of claim 1 without undue experimentation. The rejection under 35 U.S.C.
§ 112, first paragraph, for lack of enablement is affirmed. Claims 2-9, 15,
16, and 20-22 fall with claim 1.
OTHER ISSUES
If this application is subject to further prosecution, the Examiner
should consider the following issues:
A. Estrogen as SR-BI inhibitor
The Specification states that estrogen administration reduces SR-BI
expression and is therefore an SR-BI inhibitor:
Animals receiving estrogen had significantly reduced levels of
SR-BI expressed in the liver, and elevated levels of SR-BI and
fluorescence in the ovaries. Since administration of estrogen is
associated with a number of side effects, inhibition is more
preferably achieved through the use of agents which inhibit
expression of SR-BI, translation of SR-BI, binding of SR-BI, or
cellular processing mediated by the SR-BI.
(Specification 10: 29 to 11: 6.)
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The prior art teaches methods of inhibiting pregnancy comprising
administering estrogen. See, e.g., Spona et al., “Inhibition of ovulation by
an oral contraceptive containing 100 µg levonorgestrel in combination with
20 µg ethinylestradiol,” Contraception, Vol. 54, pp. 299-304 (1996) (of
record).
Some of the claims were rejected earlier in prosecution as anticipated
by Spona and other references. Those rejections were overcome by
amendments to the claims, but the amendments that overcame the rejections
have since been modified. Claim 1, as it currently stands, appears to read on
the method disclosed by Spona. Other claims may also read on Spona, or
other prior art.
If this application is subject to further prosecution, the Examiner
should consider whether the claims as they currently stand are anticipated
by, or would have been obvious in view of, methods taught in the prior art.
B. Claims 4-7
Claim 1, on which all the other claims depend, is directed to a
“method . . . comprising administering a compound inhibiting uptake,
binding or transport of cholesteryl ester by SR-BI.” Claim 4 is directed to
the same method “wherein the compound decreases SR-BI expression,”
while claim 5 is directed to the same method “wherein the compound
increases SR-BI expression.” Similarly, claim 6 is directed to the same
method “wherein the compound decreases SR-BI binding to lipoprotein,”
while claim 7 is directed to the same method “wherein the compound
increases SR-BI binding to lipoprotein.”
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If this application is subject to further prosecution, the Examiner
should consider whether compounds having diametrically opposed
mechanisms – both increasing and decreasing SR-BI expression, or both
increasing and decreasing SR-BI binding to lipoprotein – can all have the
same overall effect of inhibiting uptake, binding or transport of cholesteryl
ester by SR-BI., as required by claim 1.
C. Claim 16
Claim 16 depends on claim 11, which has been cancelled. If this
application is subject to further prosecution, the dependency of claim 16
should be corrected.
SUMMARY
We affirm the rejection of claims 1-9, 12, 15, 16, and 20-22 for lack
of adequate written description and the rejection of claims 1-9, 15, 16, and
20-22 for lack of enablement.

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
Ssc

PATREA L. PABST
PABST PATENT GROUP LLP
400 COLONY SQUARE, SUITE 1200
1201 PEACHTREE STREET
ATLANTA, GA 30361
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