Ex Parte Hogan

Board of Patent Appeals and Interferences

Jul 31, 2006

09976423 (B.P.A.I. Jul. 31, 2006)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KIRK HOGAN
__________

Appeal No. 2006-1517
Application No. 09/976,423
__________

ON BRIEF
__________

Before BARRY, ADAMS, and GRIMES, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL

This appeal involves claims to kits for determining risk of surgery- or anesthesia-
related complications. The examiner has rejected the claims as based on new matter,
anticipated, and obvious in view of the prior art. We have jurisdiction under 35 U.S.C.
§ 134. We reverse all of the rejections.
Background
“Although surgery saves many lives, surgical complications result in many
instances of mortality and morbidity. Complications related to surgery and anesthesia
include infections, excessive blood loss, thrombosis, nausea and vomiting, and
anesthesia reactions.” Specification, page 1.
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Application No. 09/976,423

Mutations in several genes have been linked to increased risk of surgery- and
anesthesia-related complications including malignant hyperthermia, sepsis, and
possible toxicity of anesthetics and other drugs. See page 2, lines 3-4 and 22-24; page
2, line 27 to page 3, line 2; and page 3, lines 12-13.
The specification discloses “a kit for generating a perioperative genomic profile
for a subject, comprising a reagent capable of detecting the presence of a variant allele
of two or more genes markers [sic] selected from [particular genes]; and instructions for
using the kit for generating the perioperative genomic profile for the subject.” Page 6,
lines 15-20.
“In some embodiments, a computer-based analysis program is used to translate
the raw data generated by the genomic profile (e.g., the presence or absence of a given
SNP [single nucleotide polymorphism; page 28, line 19] or mutation) into data of
predictive value for the clinician (e.g., probability of abnormal pharmacological
response, presence of underlying disease, or differential diagnosis of known
disease). . . . Thus, . . . the clinician, who is not likely to be trained in genetics or
molecular biology, need not understand the raw data of the genomic profile. The data is
presented directly to the clinician in its most useful form.” Page 50, lines 8-17.
“For example, in some embodiments . . . , a sample is obtained from a subject
and submitted to a genomic profiling service (e.g., clinical lab at a medical facility,
genomic profiling business, etc.) to generate raw data. . . . Once received by the
genomic profiling service, the sample is processed and a genomic profile is produced
(i.e., genomic data), specific for the medical or surgical procedure the subject will
undergo. The genomic profile data is then prepared in a format suitable for

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Application No. 09/976,423

interpretation by a treating clinician. For example, rather than providing raw sequence
data, the prepared format may represent a risk assessment for various treatment
options.” Page 50, line 22, to page 51, line 10.
Discussion
1. Claim construction
Claims 72-107 are pending and on appeal. Claims 72 and 106 are
representative and read as follows:
72. A kit for generating a perioperative genomic profile for a subject,
comprising:

a) reagents configured such that when exposed to a sample
containing target nucleic acid from a perioperative subject, said subject being a
patient scheduled for a surgical procedure that has not yet completed said
surgical procedure, are sufficient to detect the presence or absence of variant
alleles in two or more genes associated with two or more conditions selected
from the group consisting of BChE, CYP2D6, F5, F2, CACNAIS, MTHFR, MTR,
MTRR, CBS, TNFα and TNFβ so as to generate a genomic profile for use in
selecting a perioperative course of action for said subject; and

b) a computer program comprising instructions which direct a
processor to analyze data derived from use of said reagents.

106. A perioperative genomic profile kit having component parts
configured such that when exposed to a sample containing target nucleic acid
from a perioperative subject, said subject being a patient scheduled for a surgical
procedure that has not yet completed said surgical procedure, are sufficient to
detect the presence or absence of variant alleles in two or more genes
associated with two or more conditions selected from the group consisting of
BChE, CYP2D6, F5, F2, CACNAIS, MTHFR, MTR, MTRRR, CBS, TNFα and
TNFβ, so as to generate a genomic profile for use in selecting a perioperative
course of action for said subject and thereby providing a subject-specific clinical
pathway for said subject, comprising information to optimize perioperative care
that, based at least on the presence or absence of said variant alleles of two or
more genes associated with two or more conditions selected from the group
consisting of BChE, CYP2D6, F5, F2, CACNAIS, MTHFR, MTR, MTRR, CBS,
TNFα and TNFβ measured by said kit, directs a user to a specific clinical
pathway of medical intervention for said subject.

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Thus, claim 72 is directed to a kit comprising “reagents” and “a computer
program.” The claim specifies that the reagents in the kit are “configured such that
when exposed to a sample containing target nucleic acid from a perioperative subject,
. . . [they] are sufficient to detect the presence or absence of variant alleles in two or
more genes associated with two or more conditions selected from [a group of specific
genes].”
As we interpret the claim language, it requires reagents that are sufficient to
detect the presence or absence of variant alleles in at least two of the recited genes
when exposed to a sample containing a target nucleic acid. That is, the reagents in the
kit can be combined with a sample from a perioperative subject and processed to detect
the presence of variant alleles in the specified genes, without the addition of other
reagents. This interpretation is required by the claim language: if reagents not included
in the kit were required to detect the presence of variant alleles in the recited genes,
then the kit would not comprise reagents “sufficient to detect” those alleles.
The other passages in part (a) of claim 72 do not constitute limitations of the
claimed kit. The passage stating that the “subject [is] a patient scheduled for a surgical
procedure that has not yet completed said surgical procedure” recites nothing more
than an intended use of the claimed kit. That is, the specification states that the kit is
intended to be used shortly before or during surgery (see page 9, lines 3-11) but that
intended use does not limit the components of a kit: the same components would be
required to detect the presence of the recited alleles regardless of whether the kit was
used perioperatively.

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In addition, the passage stating that the reagents “generate a genomic profile for
use in selecting a perioperative course of action for said subject,” merely recites the
intended outcome of using the regents. The specification defines “genomic profile” as
“a set of information about a given ‘subject’s’ genes (e.g., the presence or absence of a
specific set of mutations or ‘SNPs’).” Page 27, lines 13-14. Thus, the “genomic profile”
recited in the claims refers simply to the data showing the presence or absence of the
recited variant alleles, and reagents that are sufficient to detect alleles in at least two of
the recited genes are therefore, by definition, capable of generating a genomic profile.
Finally, the kit defined by claim 72 comprises “a computer program comprising
instructions which direct a processor to analyze data derived from use of said reagents.”
Claim 106 is similar to claim 72 in that it requires the same reagents (which are
termed “component parts” in claim 106). As with claim 72, the claim language stating
that the “subject [is] a patient scheduled for a surgical procedure that has not yet
completed said surgical procedure” recites nothing more than an intended use of the
claimed kit, and does not further limit the claim. Likewise, the recitation “so as to
generate a genomic profile” also does not further limit the claim, because detecting the
presence or absence of alleles in at least two of the recited genes by definition
generates a genomic profile.
Finally, the claim language following “so as to generate a genomic profile” recites
nothing more than the intended use of the genomic profile that is to be generated by the
kit, and does not further limit the claimed kit. That is, the kit requires regents
(“component parts”) sufficient to detect polymorphisms in at least two of the recited
genes, thereby generating a genomic profile, but the reagents that are capable of

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Application No. 09/976,423

detecting those alleles are the same regardless of whether the resulting genomic profile
is used as recited in claim 106; the intended use language at the end of the claim
therefore does not constitute a structural limitation of the claimed kit.
Claim 106 differs from claim 72 in that it does not require the claimed kit to
comprise a computer program in addition to the component parts that detect the
presence of variant alleles.
2. Written Description
The examiner rejected claims 72-105 under 35 U.S.C. § 112, first paragraph, for
lack of adequate written description; that is, being based on new matter. The examiner
argued that “the specification does not describe or discuss ‘a computer program
comprising instructions which direct a processor to analyze data derived from use of
said reagents.” Examiner’s Answer, paragraph bridging pages 3 and 4. See also page
6: “The concept of ‘a computer program comprising instructions which direct a
processor to analyze data derived from use of said reagents’ does not appear to be part
of the originally filed invention.”
However, on page 4 of the Examiner’s Answer, the examiner quotes the
following passage from the specification: “In some embodiments, a computer-based
analysis program is used to translate the raw data generated by the genomic profile
(e.g., the presence or absence of a given SNP or mutation) into data of predictive value
for the clinician (e.g., probability of abnormal pharmacological response, presence of
underlying disease, or differential diagnosis of known disease)” (emphases added).
While this passage does not use precisely the same words as claim 72, we agree with
Appellant that it reasonably describes the limitation recited in the claim.

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The examiner also rejected the claims because “[t]here is no disclosure in the
instant specification of a kit comprising reagents and a computer program.” Examiner’s
Answer, page 4. See also page 5 (“there are no teachings of a computer program
within a kit”).
Again, however, we agree with Appellants that the specification describes the
combination of a computer program and allele-detecting reagents, although not
precisely in the terms used in the claims. The specification describes kits comprising
reagents capable of detecting variant alleles of various genes (see, e.g., page 6, lines
15-20) and describes a “computer-based analysis program . . . to translate the raw data”
generated by such kits (page 50, lines 8-12).
Moreover, the specification states that “Figure 2 illustrates the transformation of a
sample . . . into data useful for the clinician.” Page 50, lines 21-22. “[A] sample is
obtained from a subject and submitted to a genomic profiling service (e.g., clinical lab at
a medical facility, genomic profiling business, etc.) to generate raw data. . . . Once
received by the genomic profiling service, the sample is processed and a genomic
profile is produced (i.e., genomic data), specific for the medical or surgical procedure
the subject will undergo.” Page 50, line 22 to page 51, line 7.
The specification also contemplates that the party generating the genomic profile
from the sample will process the data into a more easily understood format. See page
51, lines 8-15: “The genomic profile data is then prepared in a format suitable for
interpretation by a treating clinician. For example, rather than providing raw sequence
data, the prepared format may represent a risk assessment for various treatment
options. . . . [I]n some embodiments, the genomic profiling service generates a report

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Application No. 09/976,423

that can be printed for the clinician . . . or displayed to the clinician on a computer
monitor.”
In our view, these disclosures reasonably support the concept of combining
reagents for detecting variant alleles with a computer program to analyze data indicating
the presence or absence of such variant alleles. Adequate written description does not
require literal support in the specification: “In order to satisfy the written description
requirement, the disclosure as originally filed does not have to provide in haec verba
support for the claimed subject matter at issue.” Purdue Pharma L.P. v. Faulding, Inc.,
230 F.3d 1320, 1323, 56 USPQ2d 1481, 1483 (Fed. Cir. 2000). Adequate written
description requires only a disclosure that conveys with reasonable clarity to those
skilled in the art that the inventor was in possession of the invention. See id.
In this case, we conclude that the examiner has not adequately explained why
the description provided by the specification would be considered inadequate, by those
skilled in the art, to show possession of the instanty claimed kit. We therefore reverse
the rejection based on the first paragraph of 35 U.S.C. § 112.
3. Anticipation
The examiner rejected claims 72-105 under 35 U.S.C. § 102(b) as anticipated by
Applied Biosystems,1 and rejected claims 106 and 107 as anticipated by Perkin Elmer.2
With regard to Applied Biosystems, the examiner reasoned that
Applied Biosystems provides several products which are packaged for
distribution, kits, which allow for detecting the presence of variant alleles of
two or more genes. Applied Biosystems products for sale include: a DNA
analysis system; software for genetic analysis; . . . PRISM Ready reaction

1 Sales catalog of Applied Biosystems, Inc., pp. 135-157 and 160-164 (1993)
2 PCR Systems, Reagents & Consumables catalog, Perkin Elmer, pp. 15-18 (1995)

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cycle sequencing kits; AmpliTaq Cycling Sequencing Kits; . . . etc. Each of
these products is capable of detecting the presence of variant alleles of two
or more genes. Applied Biosystems teaches numerous computer
programs which are sold with the DNA analysis system, for example.

Examiner’s Answer, page 7. Similarly, with respect to Perkin Elmer, the examiner
reasoned that
Perkin Elmer provides several products which are packaged for
distribution, kits, which allow for detecting the presence of variant alleles
of two or more genes. First, Perkin Elmer teaches the GeneAmp PCR
Reagent Kit with AmpliTaq DNA polymerase. . . . This kit provided by
Perkin Elmer contains reagents which allow for detection of variant alleles
of two or more genes.

Id., page 9.
Appellant argues that “the Examiner has ignored [certain] claim elements entirely
i.e., reagents sufficient to detect the presence or absence of variant alleles in two or
more genes associated with two or more conditions selected from the specified group
consisting of BChE, CYP2D6, F5, F2, CACNAIS, MTHFR, MTR, MTRR, CBS, TNFα
and TNFβ. . . . It is a matter of simple fact that the 1993 Applied Biosystems Product
Catalog is insufficient, standing alone, to detect the alleles of the perioperative genomic
profile kits of the present invention without more, i.e., specific reagents to do so.”
Appeal Brief, page 24. See also Reply Brief, page 11 (arguing that Perkin Elmer does
not teach kits comprising parts that are “sufficient to detect the presence or absence of
variant alleles in two or more genes associated with two or more conditions selected
from” the recited genes).
We agree with Appellant that neither Applied Biosystems nor Perkin Elmer
disclose the kits defined by instant claims 72 and 106. As Appellant points out, the
claimed kits must include reagents (or component parts) “sufficient to detect” variant

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Application No. 09/976,423

alleles in at least two of the recited genes. We agree with this interpretation of the
claims.
None of the kits disclosed by either Applied Biosystems or Perkin Elmer include
reagents that are specific to any of the genes recited in claims 72 and 106. The kits
disclosed in the references contain reagents for performing a polymerase chain reaction
(PCR) process or for carrying out DNA sequencing. Granted, the kits disclosed by the
references would allow a skilled worker to amplify and sequence any given DNA
fragment, given primers specific to the desired fragment. What is missing from the
references, however, is a disclosure of primers specific to any of the genes recited in
claims 72 and 106.
“[A]nticipation requires that all of the elements and limitations of the claim are
found within a single prior art reference.” Scripps Clinic & Research Found. v.
Genentech, Inc., 927 F.2d 1565, 1576, 18 USPQ2d 1001, 1010 (Fed. Cir. 1991).
Applied Biosystems does not disclose a product meeting all the limitations of claim 72
and Perkin Elmer does not disclose a product meeting all the limitations of claim 106.
We therefore reverse the rejections based on Applied Biosystems and Perkin Elmer.
4. Obviousness
The examiner rejected claims 106 and 107 under 35 U.S.C. § 103(a) as obvious
in view of either Rosen3 and Ahern4 or Tarkowski5 and Ahern. The examiner noted that
“Rosen teaches [that] genotyping of selected loci of the TNF-alpha and TNF-beta

3 Rosen, U.S. 2002/0119468 A1, published August 29, 2002
4 Ahern, “Biochemical, reagent kits offer scientists good return on investment,” The Scientist, Vol. 9, p. 20
(1995)
5 Tarkowski et al., “TNF gene polymorphism and its relation to intracerebral production of TNF α and TNF
β in AD,” Neurology, Vol. 54, pp. 2077-2081 (2000)

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coding regions was performed by PCR amplification and restriction digestion,”
(Examiner’s Answer, page 11) and that “Tarkowski teaches analyses of TNFalpha and
TNFbeta gene polymorphism[s],” using PCR and restriction enzyme digestion. Id., page
13.
The examiner acknowledged that neither Rosen nor Tarkowski discloses
packaging the TNF-specific reagents in a kit, but relied on Ahern to suggest that
limitation: “Ahern teaches reagent kits offer scientists good return on investment.
Ahern teaches kits save time and money because the kits already come[ ] prepared.”
Examiner’s Answer, pages 11 and 13.
The examiner concluded that it would have been prima facie obvious to package
the reagents taught by Rosen into a kit because Rosen “teaches mutations at –308 [of
TNF-α] and aa13 and aa26 [of TNF-β] which are associated with predisposition to liver
rejection.” Id., page 12. Similarly, the examiner concluded that it would have been
obvious to package Tarkowski’s reagents in a kit because “Tarkowski specifically
teaches two polymorphic genes which are associated with AD [Alzheimer’s disease].”
Id., page 13.
Appellant argues that the examiner’s rejection should be reversed because,
among other things, the cited references do not provide a sufficient suggestion or
motivation to combine their teachings. See the Reply Brief, pages 13-15 and 17-19.
We agree with Appellant that the references relied on by the examiner do not
support a prima facie case of obviousness. “[T]he Examiner bears the burden of
establishing a prima facie case of obviousness based upon the prior art. ‘[The
Examiner] can satisfy this burden only by showing some objective teaching in the prior

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Application No. 09/976,423

art or that knowledge generally available to one of ordinary skill in the art would lead
that individual to combine the relevant teachings of the references.’” In re Fritch, 972
F.2d 1260, 1265, 23 USPQ2d 1780, 1783 (Fed. Cir. 1992) (citations omitted). “[T]he
‘motivation-suggestion-teaching’ test asks not merely what the references disclose, but
whether a person of ordinary skill in the art, possessed with the understandings and
knowledge reflected in the prior art, and motivated by the general problem facing the
inventor, would have been led to make the combination recited in the claims.” In re
Kahn, 441 F. 3d 977, 988, 78 USPQ2d 1329, 1337 (Fed. Cir. 2006).
In this case, the examiner has not adequately explained why a person of ordinary
skill in the art would have been found it obvious to package the reagents taught by
either Rosen or Tarkowski into a kit that would meet the limitations of instant claim 106.
Rosen teaches a method of identifying organ donors having livers less likely to be
reinfected by hepatitis C virus (HCV). See ¶ 0007. Rosen teaches that the TNF-α gene
has a polymorphic position at –308: the allele TNF308.1 has a G at this position while
the allele TNF308.2 has an A. See ¶ 0035. Rosen also teaches that “[k]nown TNF-β
polymorphisms include the TNFc locus, the aa13 locus, the aa26 locus and the NcoI
locus.” See ¶ 0028.
Rosen amplified and sequenced polymorphic positions in the TNF-α and TNF-β
genes and found that livers from donors with the TNF308.2 allele in the TNF-α gene
were reinfected by HCV more often and more severely than livers from donors with the
TNF308.1 allele. See ¶ 0066. By contrast, “[t]here was no correlation between the
TNF-β alleles and time to recurrence, severity of recurrence or the prevalence of
rejection.” ¶ 0067.

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Thus, Rosen teaches that a polymorphism in the TNF-α gene is informative in
predicting which livers are more likely to be reinfected in HCV-infected patients, but that
polymorphisms in the TNF-β gene are not. In view of Rosen’s teaching that TNF-β-
specific primers are useless for predicting likelihood of HCV reinfection, we conclude
that the examiner has not adequately explained why Rosen would have led a person
skilled in the art to package primers specific for both TNF-α and TNF-β into a kit.
Like Rosen, Tarkowski teaches PCR primers for amplifying parts of the TNF-α
and TNF-β genes. See pages 2078-2079. Tarkowski analyzed the association
between aspects of Alzheimer’s disease (AD) and polymorphisms in the TNF-α and
TNF-β genes, but concluded that “the levels of these cytokines did not differ significantly
in patients displaying different alleles of the TNF gene.” Abstract. See also page 2080,
right-hand column, second full paragraph:
[T]he frequencies of TNFα1 versus TNFα2 alleles did not differ between
patients with AD and control subjects, suggesting a lack of association
between TNF polymorphism and the susceptibility for AD. The intrathecal
TNFα levels or the degree of cognitive deficit did not differ significantly
between the groups of AD patients with different TNFα or TNFβ gene
polymorphism, suggesting a lack of association between TNF
polymorphism and the clinical severity of AD.

(Emphases added.)
Thus, Tarkowski teaches that the TNF-α and TNF-β polymorphisms that were
examined were not associated with either the susceptibility to or the clinical severity of
Alzheimer’s disease in potential patients. In view of this teaching, we conclude that the
examiner has not adequately explained why Tarkowski would have led a skilled worker
to package the TNF-α- and TNF-β-specific primers disclosed by Tarkowski into a kit.

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Application No. 09/976,423

Other Issue
This application is said to be “a continuation-in-part of co-pending U.S.
application serial number 09/613,887” (specification, page 1), which is the subject of
appeal number 2006-1560. The claims in that application are directed to a method,
rather than a kit, for perioperative screening. The examiner rejected the claims as
obvious in view of, among other references, Pharmacogenetics6 and AAS.7
AAS discloses that different alleles of the BChE gene affect patients’ reactions to
succinylcholine (page 139, left-hand column), that “careful DNA analysis is really the
only way to establish individual BChE genotypes” (page 140, right-hand column), that
“[w]e have been able to sequence the entire BCHE coding region and consider all the
possible structural mutations using PCR amplification” (id.), and that “anesthesiologists
need to keep up to date about” the application of molecular biology tests to BChE
variants (sentence bridging pages 140 and 141).
Pharmacogenetics discloses that cytochrome P4502D6 (CYP2D6) in involved in
mediating drug biotransformation (page 309), including the transformation of codeine to
its active form (page 317, left-hand column), and that by combining “rapid and specific
PCR-based allele-specific amplification tests . . . [with] XbaI RFLP analysis, about 95
percent of all mutant alleles of CYP2D6 could be identified, allowing for the prediction of
over 90 percent of PM [poor metabolizer] phenotypes” (page 314, right-hand column).

6 The reference is cited as “Pharmacogen[e]tics, Chapter 4, pp. 309-326” in the Information Disclosure
Statement received in application 09/613,887 on April 6, 2001 (reference number 202 in the IDS).
7 La Du, “Butyrylcholinesterase variants and the new methods of molecular biology,” Acta
Anaesthesiologica Scandinavica, Vol. 39, pp. 139-141 (1995)

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On return of this application, the examiner should consider whether the
references cited in application 09/613,887, together with the prior art of record, would
support a prima facie case of obviousness with respect to any of the claims in the
instant application.
REVERSED

Lance Leonard Barry )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Donald E. Adams )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Eric Grimes )
Administrative Patent Judge )

EG/dm

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