Ex Parte Orntoft et al

Patent Trial and Appeal Board

Sep 22, 2016

12180321 (P.T.A.B. Sep. 22, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO.
12/180,321
35859 7590
Pierce Atwood LLP
100 Summer Street
Suite 2250
Boston, MA 02110
FILING DATE FIRST NAMED INVENTOR
07/25/2008 Torben Falck Orntoft
09/26/2016
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
Sorge-321 9794
EXAMINER
HIBBERT, CATHERINE S
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
09/26/2016 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):
Patent@pierceatwood.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TORBEN FALCK ORNTOFT,
THOMAS THYKJAER ANDERSEN,
LARS DYRSKJOT ANDERSEN, and
JENS LEDET JENSEN 1
Appeal2014-006792
Application 12/180,321
Technology Center 1600
Before ERIC B. GRIMES, ROBERT A. POLLOCK, and
JACQUELINE T. HARLOW, 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 predicting the likelihood of bladder cancer progression, which have been
rejected as anticipated, lacking adequate written description, and indefinite.
We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm in part and enter a new ground of rejection.
1 Appellants identify the Real Party in Interest as Catalyst Assets LLC and
AAB Patent Holding. (Appeal Br. 3.)
Appeal2014-006792
Application 12/180,321
STATEMENT OF THE CASE
The Specification states that bladder cancer can take the form of either
recurring superficial tumors (stages Ta and T 1 ), or it can progress to a
muscle invasive form (stages T2 and up). (Spec. 2.) "The ability to predict
which tumours are likely to recur or progress would have great impact on the
clinical management of patients with superficial disease, as it would be
possible to treat high-risk patients more aggressively (e.g. radical
cystectomy or adjuvant therapy)." (Id.)
Claims 1, 5, 10, 12, 13, 19, 20, 24--26, 30, 31, 33, 34, 55, 77, 78, and
86 are on appeal. Claims 1 and 55 are the independent claims and read as
follows:
1. A method of using a quantitative PCR ("QPCR") machine to
determine gene expression levels of at least one progressor gene
and at least one non-progressor gene to predict the prognosis of
an individual with an early-stage bladder cancer of epithelial
urinar; bladder tissue, comprising;
(a) collecting a sample including cells from the tissue or
expression products from the cells,
(b) using QPCR to assay the expression level of at least one
progressor gene in the sample, selected from gene Nos. 383,
346, 300, 365, 437, 364, 417, 444, 317, 427, and 287, to obtain
a value representing the gene expression level of the progressor
gene( s) and determining whether the expression level of said
progressor gene(s) is increased compared to at least one
standard expression level by comparing said value to another
value associated with a standard expression level, and
predicting an increased likelihood of bladder cancer progression
for said individual if said comparison indicates said increased
expression of said progressor gene(s); and
( c) using QPCR to assay the expression level of least one non-
progressor gene in the sample selected from gene Nos. 445,
349,280,436,373,255,426,273,320,442,440,414,333,
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Application 12/180,321
407,439,281,438,433,390,435,311,394,443,441,282,
401, 434, 352, 295, 386, 279, and 428, to obtain a value
representing the gene expression level of the non-progressor
gene( s) and determining whether the expression level of said
non-progressor gene(s) is increased compared to at least one
standard expression level by comparing said value to another
value associated with a standard expression level, and
predicting a decreased likelihood of bladder cancer progression
for said individual if said comparison indicates said increased
expression of said non-progressor gene(s).
55. A method of using a quantitative PCR ("QPCR") machine
to determine gene expression levels of certain progressor genes
and non-progressor genes to predict the prognosis of an
individual with an early-stage bladder cancer of epithelial
urinary bladder tissue comprising,
collecting a sample comprising cells from the tissue or
expression products from bladder cells from the tissue,
determining an expression pattern of a bladder cell sample, by
using QPCR to assay the expression level of gene Nos. 383,
346,300,365,437,364,417,444,317,427,287,445,349,
280,436,373,255,426,273,320,442,440,414,333,407,
439,281,438,433,390,435,311,394,443,441,282,401,
434, 352, 295, 386, 279, and 428, comparing the expression
pattern determined to a reference pattern, thereby predicting the
prognosis of the bladder cancer.
App. Br. 19 and 21 (Claims Appendix).
In response to an election of species requirement, Appellants elected
gene No. 437 as the species of progressor gene and gene No. 295 as the
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Application 12/180,321
species of non-progressor gene. (Ans. 3.) Examination has been limited to
the elected species. (Id.)
The claims stand rejected as follows:
Claims 1,5, 10, 12, 13, 19,20,24-26,30,31,33,34,55, 77, 78,and
86 (Ans. 4);
Claims 1, 5, 10, 12, 13, 19, 20, 24--26, 30, 31, 33, 34, 55, 77, 78, and
86 (Ans. 7); and
Claims 1, 5, 10, 12, 13, 24--26, 30, 31, and 55 under 35 U.S.C.
§ 102(b) as anticipated by Altieri2 (Ans. 2).
I
The Examiner has rejected all of the claims on appeal for lack of
adequate written description. The Examiner finds that the Specification does
not adequately describe the recited genes because "the genes numbering
from gene No. 1 to gene No. 562 in the instant specification in Table A are
described by their Unigene accession number." (Ans. 6.) The Examiner
reasons that identifying the genes by reference to the Unigene database
"does not provide adequate written description support for the claimed
invention as the content and numbering in Unigene database record can
change over time as the records can be updated and thus the accession
number does not represent a fixed disclosure of a sequence." (Id.)
Appellants argue that the genes recited in the claims are listed in the
Specification's Table 3, which identifies the genes in five ways: 1) the Eos
Hu03 ID from the Affymetrix microarray, 2) the Unigene ID, 3) the written
2 Altieri et al., US 2002/0160395 Al, Oct. 31, 2002.
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Application 12/180,321
description of the gene, 4) the Gene Name, and 5) the Exemplar GenBank
Accession Number. (Appeal Br. 16.) Appellants argue that "[e]ach named
gene in the Gene Name column has one or more particular sequences
(representing transcript variants) in the NCBI Nucleotide database, and the
sequence(s) which were available in the NCBI Nucleotide database in 2003
can be found in the NCBI database as well." (Id.)
We agree with Appellants that the Examiner has not shown that the
Specification fails to adequately describe the claimed method. A description
adequate to satisfy 35 U.S.C. § 112, first paragraph,
must "clearly allow persons of ordinary skill in the art to
recognize that [the inventor] invented what is claimed." In other
words, the test for sufficiency is whether the disclosure of the
application relied upon reasonably conveys to those skilled in the
art that the inventor had possession of the claimed subject matter
as of the filing date.
Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010)
(citation omitted, alteration in original).
Here, the claims are directed to a method of predicting the likelihood
of progression of bladder cancer based on the expression levels of certain
genes. The Specification describes the genes to be assayed in several ways.
For example, Table A of the Specification includes the following entries for
gene numbers 295 and 437:
GGflS GeneCh!p
#
295 EOS Hu03
4-37 EQS Hu03
Prabooe\ Unlg@ne Unlgene
a,111cJ
421311 133 Hs.283609
ciescripllon Classi-
fier
hypothetlca~ proreln Pf102032 progrn.s~
slon
422765 133 Hs.1578 tiaculoviral !AP mpeat-contain~!1Q 5 (surviviri) progres-
sion
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Table A describes the genes by, among other things, the Unigene
identification number (including Unigene Build) and a description of gene
295 as "hypothetical protein PR02032" and of gene 437 as "baculoviral IAP
repeat-containing 5 (survivin)." (Spec. 11, 15, 24.)
The Specification also describes gene numbers 295 and 437 in its
Table 3, which includes the same Unigene build 133 identification number
as Table 1, together with a description of the genes, gene names, and
exemplar accession numbers. 3 (Id. at 76-77 .)
Thus, the Specification demonstrates that the genes referred to in
claim 1 as gene numbers 295 and 437 were previously known in the art and
included in databases such as Unigene build 133 at the time the application
was filed. Appellants do not claim the genes themselves, only a method of
using the expression level of the genes to predict the likelihood of
progression of bladder cancer.
The fact that the entries for the relevant genes can be updated over
time does not mean that Appellants were not in possession of the claimed
method as of the filing date, as the claims would have been understood at
that time. See Plant Genetic Systems, N. V. v. DeKalb Genetics Corp., 315
F.3d 1335, 1345 (Fed. Cir. 2003) ("Claims are to be given their ordinary and
objective meaning as of the time of the invention."). The Examiner has not
shown that a person of ordinary skill in the art would not have recognized
possession of the claimed method, based on the knowledge in the art at the
3 In Table 3, the gene relevant to gene number 295 is identified as
"muscleblind-like protein MBLL39," but the Unigene identification number
is the same as for gene number 295 (hypothetical protein PR02032).
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time of filing, from the Specification's written description. We therefore
reverse the rejection under 35 U.S.C. § 112, first paragraph, for lack of
adequate written description.
II
The Examiner has rejected all of the claims on appeal as indefinite.
The Examiner concludes that
the genes shown in Table A are indefinite because there are
alternatives provided in the table such as being represented by a
gene name (which encompasses variants to any particular
sequence such as pertaining to variant species) or as being
represented by a Unigene Accession number (which may
represent a narrower sequence than sequences encompassed by a
gene name and which Unigene sequence is unclear [] because the
Unigene database is not a fixed numbering system.
(Ans. 7.)
The Examiner states that
[t]he gene for the elected species of gene No. 437, for example,
is recited in Table A as a Unigene accession number, followed
by the descriptive term "baculoviral IAP repeat-containing 5"
followed by the term "survivin" in parenthesis. It is unclear
whether applicants are claiming the broader breadth of
"survivin" or of the narrower scope of the sequence of the
Unigene accession number.
(Id. at 8.)
Appellants argue that this rejection should be reversed for the reasons
discussed above regarding the written description rejection and in view of
the revised Table 3 that is presented in the Evidence Appendix of the Appeal
Brief. (Appeal Br. 17.)
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Application 12/180,321
We agree with Appellants. As discussed above, claim language is
interpreted in view of its ordinary and objective meaning at the time of the
invention. See Plant Genetic Systems, 315 F.3d at 1345. The fact that the
Unigene database can be updated over time is not an adequate basis for
concluding that a skilled worker would not have known which sequence(s)
were encompassed by the gene numbers recited in the claims, at the time the
application was filed.
Because the Examiner has not shown that the scope of the claims
would have been ambiguous to a person of ordinary skill in the art as of the
filing date, we reverse the rejection under 35 U.S.C. § 112, second
paragraph.
III
The Examiner has rejected claims 1, 5, 10, 12, 13, 24--26, 30, 31, and
55 as anticipated by Altieri. (Ans. 2.) The Examiner finds that Altieri
discloses all of the limitations of claim 1, including "collecting a sample
comprising cells and expression products from the cells," and therefore
anticipates the claimed method. (Id. at 3.)
Appellants raise only one issue in their appeal of the rejection of claim
1, and so that is the only issue we will address. See 37 C.F.R.
§ 41.37(c)(l)(iv): "The arguments shall explain why the examiner erred as
to each ground of rejection contested by appellant. Except as provided for in
§§ 41.41, 41.47 and 41.52, any arguments or authorities not included in the
appeal brief will be refused consideration by the Board for purposes of the
present appeal." See also Ex parte Frye, 94 USPQ2d 1072, 1075 (BPAI
2010) (precedential) ("If an appellant fails to present arguments on a
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Application 12/180,321
particular issue ... the Board will not, as a general matter, unilaterally
review those uncontested aspects of the rejection.").
Appellants argue that Altieri does not disclose collecting a sample that
includes cells or expression products from the cells, as recited. (Appeal Br.
10.) Rather, Appellants argue, Altieri "only discusses detecting survivin in
bodily fluids and most preferably urine." (Id.) Appellants argue that Altieri
teaches not to use tissue samples because it points out the disadvantages
associated with biopsies. (Id. at 11.)
However, we agree with the Examiner that "the bodily fluid and urine
samples comprising survivin as disclosed by Altieri et al explicitly read on a
sample including an expression product from the cells (i.e., survivin is an
expression product from the cells)." (Ans. 8.) That is, survivin is expressed
by cells, and Altieri discloses detecting survivin in its samples from patients
with bladder cancer. (See, e.g., Altieri i-f 102.) Thus, Altieri's samples
contained either urinary bladder cells or expression products (e.g., survivin)
from the cells.
In addition, we note that Altieri's RT-PCR example started with
"[t]otal RNA ... isolated from urine pellets." (Id. at i-f 101.) Altieri also
refers to those pellets as "urine cell pellets," in an experiment that
"suggest[ ed] that exfoliated cancer cells passively release survivin in the
extracellular milieu." (Id. at i-f 107.) It is reasonable to conclude, therefore,
that Altieri's samples contained urinary bladder cells in addition to
expression products from the cells.
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Claims 5, 10, 12, 24--26, 30, and 31 have not been argued separately
and therefore fall with claim 1. 4 37 C.F.R. § 41.37(c)(l)(iv).
Appellants also argue that "Claim 13 requires mucosal tissue or cells,
which are not discussed in paragraph 12 of Altieri et al. as sources for
samples." (Appeal Br. 12.)
We agree with Appellants that the Examiner has not pointed to
sufficient evidence to support a finding of anticipation of claim 13. The
Examiner points to Altieri's paragraph 12, which states that bladder
"carcinoma in situ" is "limited to the bladder mucosa." However, claim 13
is directed to a PCR-based method that requires using a sample that
"comprises substantially only cells from mucosa or tumors derived from said
mucosa cells." (Appeal Br. 20 (Claims App'x).) The Examiner has not
shown where such a sample is used in Altieri's PCR-based method.
Finally, Appellants argue that "Claim 55 is not anticipated by Altieri
et al. is because it recites determining the expression levels of 43 genes, and
'comparing the reported expression pattern to a reference pattern.'" (Appeal
Br. 12.)
We agree with Appellants that the Examiner has not shown
anticipation of claim 55, which (as Appellants point out), requires assaying
the expression level of forty-three specific genes and comparing the
expression pattern to a reference pattern.
4 Appellants list claims 5 and 12 along with claim 13 as being the subject of
a separate argument, but the argument presented pertains only to claim 13.
(Appeal Br. 12.) No substantive arguments were presented with regard to
claims 5 and 12, which therefore fall with claim 1.
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The Examiner responds that claim 55 is only being examined to the
extent that it reads on the elected species (gene Nos. 295 and 437). (Ans. 9.)
That reasoning, however, misapprehends the effect of an election of species.
"In applications containing a Markush-type claim that encompasses at least
two independent or distinct inventions, the examiner may require a
provisional election of a single species prior to examination on the merits .
. . . Following election, the Markush-type claim will be examined fully with
respect to the elected species and further to the extent necessary to determine
patentability." MPEP § 803.02 (emphasis added).
Thus, an election of species is a procedural device that allows an
Examiner to begin examination of a claim that includes a Markush group
with only one of the recited species. An election of species, however, does
not allow examination of an invention different from what is defined by a
claim, including examination of a method based on the expression levels of
two genes when the claim recites a method based on the expression levels of
forty-three genes.
Because the Examiner has not shown that Altieri discloses the method
defined by claim 55, we reverse the anticipation rejection of that claim.
IV
Under the provisions of 37 C.F.R. § 41.50(b ), we enter the following
new ground of rejection: Claim 1 is rejected under 35 U.S.C. § 103(a) as
obvious based on Altieri and Mack. 5 Claim 1 is directed to a method that
comprises collecting a sample that includes cells, or expression products of
5 Mack et al., U.S. 2004/0076955 Al, Apr. 22, 2004.
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cells, from epithelial urinary bladder tissue, using quantitative PCR (QPCR)
to assay the expression level of gene numbers 437 (survivin) and 295
(PR02032), and predicting the likelihood of bladder cancer progression
based on the expression levels.
Altieri discloses that bladder cancer "usually arises from the urothelial
cells, (transitional cells) that line the bladder." (Altieri i-f 5.) Altieri
discloses assaying a fluid sample (e.g., urine) for the presence of survivin,
where the presence of survivin indicates the patient has bladder cancer. (Id.
at i-f 22.) Altieri also discloses "determining the prognosis of a patient by
detecting or quantitating the amount of survivin in the biological fluid of the
patient. In some instances, the presence of survivin indicates a poor
prognosis." (Id. at i-f 24.)
Altieri's Example 3 states that RNA was isolated from urine pellets
and subjected to RT-PCR, and the amplified cDNA was visualized. (Id. at
i-f 101.) Altieri also refers to urine pellets as "urine cell pellets." (Id. at
i-f 107.) Survivin was not found in the urine of normal volunteers but was
found in all patients with bladder cancer. (Id. at i-f 102.)
In sum, Altieri would have made obvious a method of using QPCR
(RT-PCR) to determine the expression level of survivin (gene No. 437) in a
sample that includes bladder epithelial cells or expression products of them,
and predicting likelihood of cancer progression (prognosis) based on the
expression level.
Mack discloses "genes that are up- and down-regulated in bladder
cancer cells." (Mack i-f 8.) Mack states that "[t]he identification of
sequences that are differentially expressed in bladder cancer versus non-
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bladder cancer tissue allows the use of this information in a number of
ways." (Id. at i-f 103.) Mack states that its invention relates to "the use of
such expression profiles and compositions in the diagnosis, prognosis, and
therapy of bladder cancer." (Id. at i-f 2.) Mack discloses that differential
expression can be determined, among other ways, by "quantitative reverse
transcriptase PCR." (Id. at i-f 208.)
Mack states that its "Table 8A shows about 1440 genes up regulated
in Ta or Ti [sic, T 1] bladder tumors from patients who later presented with
muscle-invasive bladder tumors (stage T2-T4)." (Id. at i-f 355.) Table 8A is
headed "Genes predictive of bladder cancer progression." (Id. at i-f 382)
Table 8A includes "hypothetical protein PR02032" (i.e., gene No. 295). (Id.
at page 133, seventh entry.)
Thus, Mack discloses using QPCR to determine PR02032 expression
levels in bladder cancer cells and comparing them with expression in
nonbladder cancer cells to determine genes that are up- or down-regulated.
Mack discloses that PR02032 is a gene that is useful in determining a
patient's prognosis because it is predictive of bladder cancer progression.
Thus, it would have been obvious, based on Altieri and Mack, to
determine the expression level of both survivin (gene No. 437) and
PR02032 (gene No. 295), in order to predict the likelihood of bladder
cancer progression. One skilled in the art would reasonably expect that a
prediction based on expression of both genes would be more accurate than a
prediction based on either one alone, because both genes were known in the
art to be useful in determining prognosis of bladder cancer. Thus, the
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method of claim 1 would have been obvious to a person of ordinary skill in
the art.
Mack does not disclose the specific interpretation given to PR02032
expression levels that is recited in claim 1. However, the interpretation of
data is a purely mental step; whether a user interprets data in a particular
way does not change the actual steps of generating those data. See, e.g., In
re Kao, 639 F.3d 1057 (Fed. Cir. 2011). One of the claims in Kao recited
"providing information" that the bioavailability of oxymorphone was
increased in subjects with renal impairment. Id. at 1064. The court held that
"[t]hough the correlation between the renal impairment and bioavailability
was not known, informing someone of the correlation cannot confer
patentability absent a functional relationship between the informing and
administering steps." Id. at 1072.
The same is true here: interpreting the meaning of an increase or
decrease in PR02032 expression does not confer patentability absent a
functional relationship between the interpretation of the data and some
active step carried out as a consequence of the interpretation.
SUMMARY
We reverse the rejections under 35 U.S.C. § 112, first paragraph, and
35 U.S.C. § 112, second paragraph.
We affirm the rejection under 35 U.S.C. § 102(b) with respect to
claims 1, 5, 10, 12, 24--26, 30, and 31 but reverse it with respect to claims 13
and 55.
We enter a new ground of rejection of claim 1 under 35 U.S.C.
§ 103(a) based on Altieri and Mack. We have only applied the rejection to
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independent claim 1, but we leave it to the Examiner to determine which, if
any, of the dependent claims should also be rejected on this basis.
TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b). Section 41.50(b) provides "[a] new ground of rejection
pursuant to this paragraph shall not be considered final for judicial review."
Section 41.50(b) also provides:
When the Board enters such a non-final decision, the appellant,
within two months from the date of the decision, must exercise
one of the following two options with respect to the new ground
of rejection to avoid termination of the appeal as to the rejected
claims:
( 1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating to
the claims so rejected, or both, and have the matter reconsidered
by the examiner, in which event the prosecution will be
remanded to the examiner. The new ground of rejection is
binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the opinion
of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the claims,
appellant may again appeal to the Board pursuant to this subpart.
(2) Request rehearing. Request that the proceeding be
reheard under§ 41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.
Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure§ 1214.01.
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AFFIRMED-IN-PART, 37 C.F.R. § 41.50(b)
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