Ex Parte Penger et al

Patent Trial and Appeal Board

Jan 31, 2017

12880001 (P.T.A.B. Jan. 31, 2017)

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.
12/880,001 09/10/2010 Anja Penger 4141.002US2 8223
21186 7590 02/02/2017
SCHWEGMAN LUNDBERG & WOESSNER, P.A.
P.O. BOX 2938
MINNEAPOLIS, MN 55402
EXAMINER
JOHANNSEN, DIANA B
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
02/02/2017 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):
uspto@slwip.com
SLW @blackhillsip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANJA PENGER, REIMUND SPRENGER, and
ULRICH BRINKMANN1
Appeal 2015-007994
Application 12/880,001
Technology Center 1600
Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and
ULRIKH W. JENKS, Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims directed
to a method of determining if a subject is at risk of increased metabolism of
a CYP2C8 substrate. The Examiner rejects the claims as indefinite, lacking
descriptive support, lacking enablement, as well as being directed to patent
ineligible subject matter. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 According to Appellants, the real party in interest is Transgenomic, Inc.
(App. Br. 2.)
Appeal 2015-007994
Application 12/880,001
STATEMENT OF THE CASE
Claims 29 and 42—56 are on appeal2, and a copy of the claims under
consideration can be found in the Appellants’ response filed April 3, 2013.
Claim 42 is representative of the claims on appeal, and reads as follows:
42. A method for treating a human subject at risk for increased
metabolism of a CYP2C8 substrate comprising the steps of:
(a) detecting in a CYP2C8 polynucleotide in the genome
of the human subject at least one copy of a G at the position
corresponding to position 1668 of SEQ ID NO: 400;
(b) identifying the human subject having at least one
copy of a G at said position as being at risk for increased
metabolism of the CYP2C8 substrate relative to the metabolism
of the CYP2C8 substrate of a human subject having two copies
of a T at said position; and
(c) treating the human subject identified as being at risk
for increased metabolism of the CYP2C8 substrate with an
individualized therapy, wherein the individualized therapy is
different from a conventional CYP2C8 substrate therapy for a
human subject having two copies of a T at said position.
The following grounds of rejection are before us for review:
I. claims 29, 42—50, 52, 54, and 56 under 35 U.S.C. § 112, second
paragraph, as being indefinite;
II. claims 42—50 and 54—56 under 35 U.S.C. § 112, first paragraph,
as failing to comply with the written description requirement in that they
contain new matter;
2 The Examiner notes that “the after final amendment of November 21, 2014
has not been entered (see the Advisory action mailed December 19, 2014,
particularly at Box 7). The claims on appeal are thus the finally rejected
claims (claim set of April 3, 2013).” Ans. 12. Specifically, it is noted that
claims 44 and 56 as they appear in the Claims Appendix of the Appeal Brief
do not correspond to the claims under appeal. Id.
2
Appeal 2015-007994
Application 12/880,001
III claims 42—50, 54, and 56 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the enablement requirement; and
IV. claims 29, 42^49, 51—53, and 56 under 35 U.S.C. § 1013 as
being directed to patent ineligible subject matter.
I Indefiniteness
Claim 52
Claim 52 recites the limitation of “a polynucleotide that specifically
hybridizes to a CYP2C8 polynucleotide comprising a G at position 1668 of
SEQ ID NO: 400.” With respect to this claim, the Examiner’s position is
that “[njeither the specification nor the prior art provide a limiting definition
of the term ‘specifically hybridizes,’ and it is thus not clear what types of
polynucleotides are embraced by (and excluded from) claim 52.” Final
Act. 5. As written, the claims “encompass any ‘use’ in ‘detecting’ of a
polynucleotide as recited in claim 52; there is no requirement in the claim
for any type of allele-specific hybridization based assay, for a probe/primer
that shares any particular structure with the recited polynucleotide, etc.”
Ans. 4.
Appellants contend that it was known in the art to design probes “that
hybridize to one form of a biallelic marker and not to the other.” Brief 8.
We find that Appellants have the better position. According to the
Specification:
The term “stringent hybridization conditions” is well known in
the art; see, for example, Sambrook et al., ‘Molecular Cloning,
A Laboratory Manual’ second ed., CSH Press, Cold Spring
3 The Examiner withdrew the 35 U.S.C. § 101 rejections with respect to
claims 50, 54, and 55. Answer 2.
3
Appeal 2015-007994
Application 12/880,001
Harbor, 1989; “Nucleic Acid Hybridisation, A Practical
Approach”, Hames and Higgins eds., IRL Press, Oxford, 1985.
Spec. 30.
We understand the Examiner’s rejection is directed at the possibility
that the claims may encompass nucleic acid probes that do not necessarily
overlap the particular position 1668 of SEQ ID NO: 400. We are not
persuaded by the Examiner’s rationale. Here, the Specification directs us to
generic references that discuss cloning and primer selection generally.
These references in conjunction with knowledge of the 2097 bases that make
up SEQ ID NO: 400 as disclosed in the Specification, in addition to the
knowledge of the particular mutation position 1668, would lead one of
ordinary skill to design a probe that targets the area encompassing position
1668 in order to distinguish mutants at that location. The preponderance of
evidence of record does not support the Examiner’s position that the claim
52 is indefinite.
Claims 42—46 and 49
Claim 42 recites “individualized therapy, wherein the individualized
therapy is different from a conventional CYP2C8 substrate therapy for a
human subject having two copies of a T at said position.” The Examiner’s
position is that claim 42 is indefinite because “the specification does not
teach what might constitute an ‘individualized therapy as specified in the
claims, and particularly does not teach what would be considered
conventional/different from conventional with respect to ‘a human subject
having two copies of a T’ at the claimed position.” Final Act. 5. “[T]he
claims actually require ‘treating’ a subject with a particular type of
‘individualized therapy’ relative to that which is ‘conventional... for a
4
Appeal 2015-007994
Application 12/880,001
human subject having’ a specific CYP2C8 genotype.” Answer 14. With
respect to claim 44 the Examiner finds that “[t]he specification does not
make clear what would/would not be considered a ‘conventional’ dose of
such a substrate and/or a dose that is ‘different from a conventional dose.’”
Final Act. 6. In other words, the Examiner finds that the “required steps of
treating/selecting/administering were not disclosed in the application as
filed.” Answer 14.
Appellants contend that the Specification shows that individuals have
a different enzyme activity based on the presence or absence of G at position
1668 in SEQ ID NO: 400. See Brief 9. Appellants contend that “drugs that
are CYP2C8 substrates are known, as are the common indications that are
treated by those drugs. It is logical to conclude that there are conventional
doses and regimens for each drug and indication.” Brief 10.
We are not persuaded. Even with the understanding that allelic
variants process their substrates at different rates, this does not clarify what
is encompassed by “conventional therapies.” Because “conventional
therapies” associated with CYP2C8 are neither disclosed in the Specification
nor readily understood from the art generally, we agree with the Examiner’s
position that the metes and bounds of these claims is not clear. Accordingly,
we affirm the Examiner’s rejection of claims 42 46 and 49 as being
indefinite.
Claim 46
The Examiner finds that the claim lacks antecedent basis for the
limitation ‘the xenobiotic CYP2C8 substrate.’” Final Act. 6.
5
Appeal 2015-007994
Application 12/880,001
Appellants do not identify any error in the Examiner’s indefiniteness
rejection. We therefore summarily affirm the indefmiteness rejection based
upon the Examiner’s explanation and reasoning. Id.
Claims 4 7, 48, and 56
The Examiner finds that the claims are indefinite because the
Specification does not disclose “the types of dosages/dosage regimens that
are embraced by (and excluded from) the claims.” Final Act. 6.
Appellants contend that the Specification shows that individuals have
a different enzyme activity based on the presence or absence of G at position
1668 in SEQ ID NO: 400. See Brief 11. Appellants contend that “drugs that
are CYP2C8 substrates are known, as are the common indications that are
treated by those drugs. It is logical to conclude that there are conventional
doses and regimens for each drug and indication.” Id. at 10.
We are not persuaded. Even with the understanding that allelic
variants process their substrates at different rates, this does not clarity what
is encompassed by “conventional dosage regimen.” Because conventional
dosages of CYP2C8 substrates are neither disclosed in the Specification nor
readily understood from the art generally, we agree with the Examiner’s
position that the metes and bounds of these claims are not clear.
Accordingly, we affirm the Examiner’s rejection of claims 47, 48, and 56 as
being indefinite.
Claims 50, 54, and 56
The Examiner finds that the claims are indefinite because “defining
the dosages as ‘different’ from one another does not make clear what is
actually embraced by the claims.” Final Act. 8. The Examiner finds that the
claims are indefinite because it is unclear as to “what actually constitutes a
6
Appeal 2015-007994
Application 12/880,001
first and second dosage embraced” by the claims. Id. “Additionally (and as
discussed in the original rejection), the claims are directed to a method of
treating a single human subject, and thus would require administering either
the first or second dosage referenced in claim 50 (but not both).” Ans. 11.
Appellants contend that the Specification shows that individuals can
have different enzyme activity based genotype of CYP2C8. See Brief 12.
Appellants contend that “the individual with at least one G at position 1668
will likely receive a different dosage regimen than the individuals that are
homozygous T at position 1668, for that substrate to be effective, i.e., the
first and second dosage regimens are different.” Id.
We are not persuaded. Even with the understanding that allelic
variants process their substrates at different rates, this does not clarity “what
might constitute an appropriate dosage regimen with respect to either type of
individual specified in the claim.” Ans. 11. Because therapies associated
with CYP2C8 are neither disclosed in the Specification nor readily
understood from the art generally, we agree with the Examiner’s position
that the metes and bounds of these claims are not clear. Accordingly, we
affirm the Examiner’s rejection of claims 50, 54, and 56 as being indefinite.
II. New Matter
The Examiner’s position is that the originally filed “specification does
not disclose what might constitute an ‘individualized therapy’ as specified in
the claims, and particularly does not teach what would be considered
conventional/different from conventional with respect to ‘a human subject
having two copies of a T’ at the claimed position.” Final Act. 9, see also id.
at 11. “[T]he specification as filed [also] does not disclose what might
7
Appeal 2015-007994
Application 12/880,001
constitute a ‘dosage regimen is different from a conventional dosage
regimen of the xenobiotic CYP2C8 substrate for a human subject having two
copies of a T at said position.’” Final Act. 11. Therapies directed at the use
“of ‘first’ and ‘second’ dosages set forth in the claims [also] lack basis in the
original application.” Id. at 12. The claims “embrace administering any non
CYP2C8 substrate to a subject with one particular genotype and
administering any xenobiotic CYP2C8 substrate to a subject having a
different particular genotype, [this too was] not disclosed in the application
as filed.” Id. at 13. Because the claimed subject matter identified by the
Examiner does not find support in the original application the claims are
rejected as containing new matter.
We have reviewed, but are not persuaded by, Appellants’ contention
that the Specification provides sufficient descriptive support for the
invention as presently claimed including the recited therapies. See Brief 13—
16. Appellants contend that they need only supply detail of those elements
that are “new and not conventional.” Id. at 15. We agree with the Examiner
that the as-filed the Specification does not provide sufficient description of
the claim limitations of “individualized” and “conventional” therapies.
Appellants contend that “[t]he concept of individualized therapies
(e.g., personalized medicine) based on genotyping was recognized by the
art.” Br. 15. “In the context of population variability with regard to drug
therapy, pharmacogenomics has been proposed as a tool useful in the
identification and selection of patients which can respond to a particular
drug without side effects.” Spec. 11; Brief 13. Specifically, the
Specification explains that “suitable individual therapy can be designed
based on the knowledge of the individual genetic makeup of a subject with
8
Appeal 2015-007994
Application 12/880,001
respect to the polynucleotides of the invention and improved therapeutics
can be developed.” Spec. 13—14.
A showing that the concept of individual therapy is known and
recognized in the art is not sufficient to establish that the Specification
contains a description of the subject matter as claimed. As explained by the
Examiner “the claims actually require ‘treating’ a subject with a particular
type of ‘individualized therapy’ relative to that which is ‘conventional. . . for
a human subject having’ a specific CYP2C8 genotype.” Answer 14. It is
“[tjhese required steps of treating/selecting/administering [that] were not
disclosed in the application as filed.” Id.
We agree with the Examiner that a showing “that certain therapies
were known to be ‘conventional’ in a subject having one genotype with
respect to a previously unknown variant is not persuasive.” Answer 15. In
other words, showing that such individualized therapy has been established
for a different gene variant has no bearing on what is disclosed in the
Specification with respect to CYP2C8. It is the lack of description in the
Specification of therapies associated CYP2C8 that is the basis for the new
matter rejection. The presently claimed treatment for different CYP2C8
genotypes is not disclosed. Establishing that it is possible to test substrates
is not sufficient to establish treatment for the subjects. “[I]t is the
specification itself that must demonstrate possession. And while the
description requirement does not demand any particular form of disclosure, .
. . or that the specification recite the claimed invention in haec verba, a
description that merely renders the invention obvious does not satisfy the
requirement.” Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d
1336, 1352 (2010).
9
Appeal 2015-007994
Application 12/880,001
The preponderance of the evidence of record supports the Examiner’s
conclusion that the Specification does not disclose treatment regimens and
therefore adding limitations to “individualized therapy” is new matter. We
thus affirm the rejection of claims 42—50 and 54—56 under 35 U.S.C.
§ 112(a) as containing new matter.
III. Enablement
The Examiner rejects claims 42—50, 54, and 56 as failing to comply
with the enablement requirement of 35 U.S.C. 112, first paragraph. Final
Act. 13—15. “The specification is silent with regard to what types of
therapies, dosages, etc., are actually required by the claims (and this
information is not provided in the claims themselves).” Final Act. 14.
“[N]o quantity of experimentation would be sufficient to enable the use of
applicant’s claims.” Id. at 15. “[Wjhile the specification is enabling with
regard to the use of the ‘detecting’ of the claims in a variety of ways, it is not
enabling with regard to methods requiring the specific
treating/administering/selecting/etc. steps of the claimed invention.”
Answer 17.
We find that Appellants have the better position. Appellants contend
that is was known in the art “that certain polymorphisms can affect the
toxicity of drugs or the half-life of a drug with the result that a much lower
dose may be required in certain subpopulations.” Brief 16. “The
enablement requirement is often more indulgent than the written description
requirement. The Specification need not explicitly teach those in the art to
make and use the invention; the requirement is satisfied if, given what they
already know, the Specification teaches those in the art enough that they can
10
Appeal 2015-007994
Application 12/880,001
make and use the invention without ‘undue experimentation.’” Amgen, Inc.
v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1334 (Fed. Cir. 2003).
Here, the art establishes that genetic polymorphisms in the human
CYP2C subfamily have been shown to affect the metabolism of a variety of
drugs. Brief 16. Goldstein4 classifies patients into poor drug metabolizers
and efficient drug metabolizers depending on their genetic makeup, so the
drug dose can be adjusted so that toxic levels do not accumulate. Goldstein
explains that “the clinical consequences of these rarer polymorphisms can be
severe. Severe and life-threatening bleeding episodes have been reported in
CYP2C9 PMs [(poor metabolizers)] exposed to warfarin.” Goldstein,
Abstract. As pointed out by Appellants, “[t]he specification discloses that
individuals with at least one G at position 1668 have increased CYP2C8
substrate metabolizing activity (IM/EM) relative to individuals that are
homozygous T at position 1668 (they have reduced CYP2C8 substrate
metabolizing activity (PM)).” Brief 16. The Specification also provides a
list of known substrates for CYP2C8. See Spec. 2. We agree with
Appellants’ position that, based on the combination of what is known in the
art with respect to other CYP2C polymorphisms in conjunction with what is
disclosed in the Specification, one of skill in the art would know “to monitor
patients such as those with at least one G at position 1668, that are
administered a drug that may be metabolized by CYP2C8, or to adjust the
dose or dosages of that drug so that the treatment will be more efficacious.”
Brief 16-17. “That some experimentation may be required is not fatal; the
4 Goldstein, Clinical relevance of genetic polymorphisms in the
human CYP2C subfamily, 52 Br. J. Clin. Pharmacol. 349-355 (2001).
11
Appeal 2015-007994
Application 12/880,001
issue is whether the amount of experimentation required is ‘undue.’” In re
Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (emphasis in original).
In sum, as we are not persuaded, for the reasons discussed, that the
Examiner has adequately established that the claims are not enabled for the
recited treating/administering/selecting/etc. steps as claimed. Accordingly
we reverse the rejection of claims 42—50, 54, and 56 under 35 U.S.C. § 112,
first paragraph, as not being enabled.
IV. Claims Directed to Patent Ineligible Subject Matter
The Examiner has rejected claims 29, 42-49, 51—53, and 56 on appeal
as directed to patent-ineligible subject matter. The Examiner finds that the
claims are “not directed to patent eligible subject matter . . . [because they
are] directed to a law of nature/natural principle.” Final Act. 15. The
Examiner analyzes the claims based on the USPTO’s guidance on subject
matter eligibility {id. at 15—18) and concludes that “the claims encompass
general categories of well-known, conventional methodologies, and thus do
not add any elements/steps that amount to significantly more than a natural
principle.” Id. at 16. “The claim[s] lack[] any active steps related to
detecting/determining the genotype in question (which steps might result in
the claim amounting to ‘significantly more’ than a natural principle).” Id. at
18.
Appellants do not contest that “[t]he occurrence of genetic variation,
e.g., in a CYP2C8 gene, is a naturally occurring phenomenon.” Brief 18.
With respect to the independent claims Appellants contend that the claimed
subject matter “is significantly more than the exception itself and has
meaningful limitations beyond generally linking the use of the judicial
12
Appeal 2015-007994
Application 12/880,001
exception to a particular technological environment.” Brief 19, see 20—23.
Appellants contend that “by identifying a certain specific genetic variation at
a particular position in a CYP2C8 gene relative to a different genetic
composition at that position, [each independent claim] is directed to subject
matter that is more than well-understood, routine or conventional in the
relevant art.” Brief 19, see 20-23.
We agree with the Examiner that the claims are directed to a patent-
ineligible method for the reasons set out in the Final Action mailed
December 30, 2013 and Answer which we adopt and incorporate herein by
reference. We provide the following additional comment to argument set
forth in the Appeal Brief. In Mayo Collaborative Services v. Prometheus
Labs., Inc., 132 S. Ct 1289 (2012), the Court considered a claimed method
that required administering a drug, determining the level of a metabolite of
the drug in the subject, and using certain thresholds of metabolite level to
indicate a need to increase or decrease dosage of the drug. Id. at 1295.
The Court noted that the claims “set forth laws of nature—namely,
relationships between concentrations of certain metabolites in the blood and
the likelihood that a dosage of a thiopurine drug will prove ineffective or
cause harm.” Id. at 1296. The Court held that the dispositive question was:
“do the patent claims add enough to their statements of the correlations to
allow the processes they describe to qualify as patent-eligible processes that
apply natural laws?” Id. at 1297.
The Court held that the claim’s “administering” step, “determining”
step, and “wherein” clauses did not transform the claim into a patentable
application of a natural law, id. at 1297—98: “The upshot is that the three
13
Appeal 2015-007994
Application 12/880,001
steps simply tell doctors to gather data from which they may draw an
inference in light of the correlations.” Id. at 1298.
The Court’s analysis in Mayo is directly applicable to any one of the
independent claims 29, 42, 47, and 49, which only require detecting a
nucleotide at the position corresponding to position 1668 of SEQ ID
NO: 400. Just as in Mayo, the claims inform a relevant audience of a law of
nature and “any additional steps consist of well-understood, routine,
conventional activity already engaged in by the scientific community.” Id.
Thus, the claims are directed to a patent-ineligible natural phenomenon or
law of nature.
Appellants argue that “by identifying a certain specific genetic
variation at a particular position in a CYP2C8 gene relative to a different
genetic composition at that position, [each independent claim] is directed to
subject matter that is more than well-understood, routine or conventional in
the relevant art.” Brief 19, see 20-23.
This argument is unpersuasive. The detecting step of any one of
claims 29, 42, 47, and 49 is directed to determining a specific genetic
variation at a particular position in CYP2C8, namely determining the
nucleotide at the position corresponding to position 1668 of SEQ ID
NO: 400. This assay step is narrower than the one recited in the claimed
method in Mayo, which encompassed “determining] the level of the
relevant metabolites in the blood, through whatever process the doctor or the
laboratory wishes to use.” Mayo, 132 S.Ct at 1297. We conclude, however,
that this distinction does not make any one of claims 29, 42, 47, and 49
patent-eligible. The Mayo Court noted that “methods for determining
metabolite levels were well known in the art. . . . Thus, this step tells
14
Appeal 2015-007994
Application 12/880,001
doctors to engage in well-understood, routine, conventional activity
previously engaged in by scientists who work in the field.” Id. at 1297—98.
The Court concluded: “Purely ‘conventional or obvious’ ‘[pre]-
solution activity’ is normally not sufficient to transform an unpatentable law
of nature into a patent-eligible application of such a law.” Id. at 1298,
alteration in original. The same analysis applies here. Detecting the
presence of a polynucleotide substitution at a particular location requires
only conventional and routine assays. Appellants’ Specification, in fact,
acknowledges that “[t]he methods of the mutation analysis followed
standard protocols and are described in detail in the Examples.” Spec. 12.
The “methods encompass for example haplotype analysis, single-strand
conformation polymorphism analysis (SSCA), PCR and direct sequencing.”
Spec. 12—13. Thus, the inclusion of the detecting step in the claimed method
does not transform the claim into a patent-eligible application of a law of
nature.
For the reasons discussed above, we affirm the rejection of
independent claims 29, 42, 47, and 49 under 35 U.S.C. § 101. Claims 43—
46, 48, 51—53, and 56 fall with claim the independent claims. 37 C.F.R.
§ 41.37(c)(l)(iv).
15
Appeal 2015-007994
Application 12/880,001
SUMMARY
We affirm the rejection of claims 29, 42—50, 54, and 56 under
35 U.S.C. § 112, second paragraph, as being indefinite.
We reverse the rejection of claim 52 under 35 U.S.C. § 112, second
paragraph, as being indefinite.
We affirm the rejection of claims 42—50 and 54—56 under 35 U.S.C.
§112, first paragraph, as containing new matter.
We reverse the rejection of claims 42—50, 54, and 56 under 35 U.S.C.
§112, first paragraph, as not being enabled.
We affirm the rejection of claims 29, 42-49, 51, 52, 53, and 56 under
35 U.S.C. § 101 as being directed to patent ineligible subject matter.
TIME PERIOD FOR RESPONSE
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
16