Ex Parte Nuijen et al

Patent Trial and Appeal Board

Sep 25, 2017

14173734 (P.T.A.B. Sep. 25, 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.
14/173,734 02/05/2014 Bastiaan Nuijen 1948361.00146 CON 7073
45200 7590 09/27/2017
K&L Gates LLP-Orange County
1 Park Plaza
Twelfth Floor
IRVINE, CA 92614
EXAMINER
PAK, JOHN D
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
09/27/2017 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):
uspatentmail@klgates.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BASTIAAN NUJIEN, ERNIE PFADENHAUER,
JOS H. BEIJNEN, LUIGI LENAZ, SHANTA CHAWLA, and
MARIO BEER1
Appeal 2017-003041
Application 14/173,734
Technology Center 1600
Before ULRIKE W, JENKS, JOHN E. SCHNEIDER,
and RACHEL H. TOWNSEND, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 (a) involving claims to
methods for treating bladder cancer which have been rejected for improper
dependent form and/or as obvious. We have jurisdiction under 35 U.S.C.
§ 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as Spectrum Pharmaceuticals,
Inc. Appeal Br. 3.
Appeal 2017-003041
Application 14/173,743
STATEMENT OF THE CASE
Bladder cancer is one of the most common types of cancer in the
world. Spec. 13. Management of bladder cancer may be achieved by
transurethral resection where all visible lesions are removed. Spec. 1 6.
“Transurethral resection of bladder tumor (TUR-BT) is often followed by a
course of adjuvant intravesical chemotherapy or immunotherapy with the
aim of both eradicating remaining tumor cells and preventing tumor
recurrence.” Id. The Specification describes the use of Apaziquone as a
treatment of bladder cancer following TUR-BT. Spec. H 11—14.
Claims 1—3, 7—11, 13, and 16 are on appeal. Claims 1 and 16 are the
sole independent claims and read as follow:
1. A method of treating bladder cancer comprising
administering a therapeutic composition comprising a
therapeutic amount of Apaziquone immediately after
transurethral resection of bladder tumor (TUR-BT).
16. A method of treating bladder cancer comprising the
steps of:
(a) performing transurethral resection of a bladder tumor
in patients in need thereof; and
(b) administering via intravesical instillation a
therapeutically effective amount of Apaziquone.
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The claims stand rejected as follows:
Claims 1—3, 7—11, 13, and 16 have been rejected under 35 U.S.C.
§ 103(a) as unpatentable over Nuijen2 in view of Oosterlinck3 and Wientjes.4
Claim 3 has been rejected under 35 U.S.C. § 112 fourth paragraph as
being in improper dependent form.5
OBVIOUSNESS
Issue
The issue with respect to this rejection is whether a preponderance of
evidence supports the Examiner’s finding that claims 1—3, 7—11, 13, and 16
would have been obvious over Nuijen combined with Oosterlinck and
Wientjes.
The Examiner finds that Nuijen discloses the use of Apaziquone to
treat superficial bladder cancer following TUR-BT, but does “not specify
administering their compositions ‘immediately after’ TUR-BT.” Final Act.
4—5. Oosterlinck teaches administration of a chemotherapeutic agent
immediately following TUR. Final Act. 5. Wientjes teaches that
administration of a chemotherapeutic agent following TUR reduces the
likelihood of blabber cancer recurring by tumor cells dislodged by resection.
2 Nuijen et al., US 2003/0133954 Al, published July 17, 2003 (“Nuijen”).
3 Oosterlinck et al., Guideline on Bladder Cancer, 41 European Urology 105
(2002) (“Oosterlinck”).
4 Wientjes et al., Bladder Wall Penetration of Intravesical Mitomycin C in
Dogs, 51 Cancer Res. 4347 (1991) (“Wientjes”).
5 Appellants also present arguments relating to a rejection of the claims as
obvious over Mirejovsky et al., US 2007/0185188, published Aug. 9, 2007.
We have not considered these arguments as the Examiner has noted that this
rejection was not maintained in the Final Action. Ans. 2.
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Application 14/173,743
which may implant to form secondary tumors. Id. The Examiner concludes
that
the claimed invention, as a whole, would have been prima facie
obvious to one of ordinary skill in the art at the time the
invention was made, because every element of the invention
and the claimed invention as a whole have been fairly disclosed
or suggested by the teachings of the cited references.
Final Act. 6.
Appellants contend that Nuijen does not teach or suggest
administering Apaziquone in any specific time frame. Appeal Br. 9.
Appellants contend that despite the teachings of Oosterlinck, one skilled in
the art would not have been motivated to administer Apaziquone within 6
hours of TUR. Id. Appellants also argue that one skilled in the art would
not have had a reasonable expectation of success that the use of Apaziquone
within six hours of TUR would have been successful. Id. at 9—10.
Appellants contend that the Examiner engaged in improper hindsight in
reaching a conclusion of obviousness. Id. at 10.
Findings of Fact
We adopt the Examiner’s findings as our own, including with regard
to the scope and content of, and motivation to modify or combine, the prior
art. The following findings are included for emphasis and reference
purposes.
FF1. Nuijen discloses the use of Apaziquone for “intravesical
instillation to treat bladder cancer.” Nuijen | 5.
FF2. Nuijen teaches that while Apaziquone was reported to fail in
several clinical trials, Nuijen teaches that the problems encountered using
Apaziquone to treat systemic cancers
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may be advantageous for treating cancers which arise in a third
compartment such as superficial bladder cancer. In this
scenario, drug delivery is not problematical via the intravesical
route and the penetration of E09 into avascular tissue can be
increased by maintenance of therapeutically relevant drug
concentrations within the bladder (using a one hour instillation
period for example). While this method of instilling E09 within
the bladder may be useful, there still remains a need for drug
delivery vehicles that are capable of delivering an effective
amount of E09 within the bladder.
Nuijen 14.
FF3. Nuijen teaches that Apaziquone (E09) can be used in amounts
ranging from 0.5 mg to about 16 mg. Nuijen 112.
FF4. Nuijen states that “[t]he results of this study provide strong
evidence in support of the proposal that intravesical administration of E09
may have activity against bladder tumors.” Nuijen 139.
FF5. Oosterlinck teaches that
Immediate instillation after TUR with a chemotherapeutic
agent should be encouraged in all cases as it is
able to reduce recurrence rate by about 50% [11,12], In
intermediate risk tumours that needs a further instillation,
an early instillation can reduce the need for maintenance
therapy [13]. Low-risk tumours need no further treatment.
Oosterlinck 106, col. 2.
FF6. Oosterlinck goes on to teach that
Tumours with a higher risk of recurrence should be
treated with a 4—8-week-course of bladder instillation.
Severe bladder irritation is a reason to delay or stop the
treatment to avoid invalidating symptoms for the
patient and later bladder contraction. Side effects are
related to the intensity of the treatment regimen.
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Id.
FF7. Wientjes teaches that one type of target cells for intravesical
chemotherapy is tumor cells which become dislodged during resection
which may implant to form secondary tumors. Wientjes 4347.
FF8. Wientjes also teaches that tumor classified as Ta respond more
favorably to intravesical chemotherapy than Ti tumors. Id.
Principles of Law
“[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting a prima facie case of unpatentability. If
that burden is met, the burden of coming forward with evidence or argument
shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
A proper § 103 analysis requires “a searching comparison of the
claimed invention—including all its limitations—with the teaching of the
prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995).
“The consistent criterion for determination of obviousness is whether
the prior art would have suggested to one of ordinary skill in the art that this
process should be carried out and would have a reasonable likelihood of
success, viewed in the light of the prior art. Both the suggestion and the
expectation of success must be founded in the prior art, not in the applicant’s
disclosure.” In re Dow Chemical Co., 837 F.2d 469, 473 (Fed. Cir. 1988).
“Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. . . . [The reference] must be read, not in
isolation, but for what it fairly teaches in combination with the prior art as a
whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
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“Any judgment on obviousness is in a sense necessarily a
reconstruction based upon hindsight reasoning, but so long as it takes into
account only knowledge which was within the level of ordinary skill at the
time the claimed invention was made and does not include knowledge
gleaned only from applicant’s disclosure, such a reconstruction is proper.”
In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971).
“A prima facie case of obviousness typically exists when the ranges of
a claimed composition overlap the ranges disclosed in the prior art.” In re
Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003).
Analysis
We find the Examiner has established that the claims would have been
obvious over Nuijen combined with Oosterlinck and Wientjes. Appellants
have not produced evidence showing, or persuasively argued, that the
Examiner’s determinations on obviousness are incorrect. Only those
arguments made by Appellants in the Briefs have been considered in this
Decision. Arguments not presented in the Briefs are waived. See 37 C.F.R.
§ 41.37(c)(l)(iv) (2015). We have identified claim 1 as representative;
therefore, all claims, except those addressed below, fall with claim 1. We
address Appellants’ arguments below.
Appellants contend that the teachings of Oosterlinck as limited to the
specific agents described in studies cited by Oosterlinck and do not apply to
all chemotherapeutic agents. Appeal Br. 8—9. Appellants argue that
Oosterlinck does not teach that the use of Apaziquone is safe and tolerable
when administered immediately after TUR. Id. To support these arguments,
Appellants point to the portion of Oosterlinck where it states that “[sjevere
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bladder irritation is a reason to delay or stop treatment.” Id. (quoting
Oosterlinck 106.)
We are unpersuaded by Appellants’ arguments. We agree with the
Examiner Ans. 4., that the teachings of Oosterlinck are not limited to the two
agents specifically mentioned in the studies Oosterlinck cites as support for
the statement with respect to treatment guidelines that “[ijmmediate
instillation after TUR with a chemotherapeutic agent should be encouraged
in all cases as it is able to reduce recurrence rate by about 50% [11,12]” FF5.
We find that Oosterlink’s treatment guideline embraces all chemotherapeutic
agents known to treat bladder cancer in light of the fact that. Oosterlinck
recommends treatment with a chemotherapeutic agent and not the specific
agents of the studies that Oosterlinck cites. FF5.
Turning to the lack of teaching in Oosterlinck regarding Apaziquone,
the Examiner does not rely on Oosterlinck to teach that Apaziquone was
known to be used to treat bladder cancer. Appeal Br. 8. Nuijen teaches the
use of Apaziquone to treat bladder cancer FF1, and is the reference the
Examiner relied upon in that regard. Final Act. 4—5.
Appellants’ argument that Oosterlinck teaches that immediate
administration of a chemotherapeutic agent would cause irritation and that
this would lead one skilled in the art not to use Apaziquone is misplaced.
Appeal Br. 9. While Appellants correctly quote a portion of Oosterlinck, the
paragraph from which the quote is taken does not address concerns with the
immediacy of administration of a chemotherapeutic but refers to side effects
which might occur during the course of a 4 to 8 week course of bladder
instillation. FF6. We agree with the Examiner that the discussion of
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possible side effects in Oosterlinck would not dissuade one skilled in the art
from using a chemotherapeutic such as Apaziquone for immediate
instillation following TUR. Ans. 5—7.
Appellants argue that Nuijen is silent as to the time frame for
application of Apaziquone and that one skilled in the art would not consider
using Apaziquone for immediate instillation. We remain unpersuaded.
Appellants’ argument is an attack on the teachings of Nuijen alone and not
in context with teachings of Oosterlinck and Wientjes. We agree with the
Examiner that the combined teachings of the references would lead one
skilled in the art to administer Apaziquone immediately after TUR to
prevent dislodged tumor cells from forming secondary tumor and to
significantly reduce the recurrence of bladder cancer. Ans. 4; FF 4, 5, 7, and
8.
Appellants argue that one skilled in the art would not have a
reasonable expectation of success in using Apaziquone for immediate
instillation following TUR. Appeal Br. 9—10. This argument is
unpersuasive. Nuijen clearly teaches the efficacy of Apaziquone against
bladder tumors and recommends its use. FF4. Oosterlinck teaches that
administration of a chemotherapeutic agent immediately after TUR has
significant benefits. FF5. Moreover, as the Examiner points out, Nuijen
teaches that Apaziquone is effective at reduced doses which reduces toxicity
and the risk of adverse side effects. Ans. 5; Nuijen 139. In light of these
facts, we agree with the Examiner that there would have been a reasonable
probability of success. Id.
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Appellants contend that the Examiner has engaged in impermissible
use of hindsight. Appeal Br. 10. Appellants argue that since Oosterlinck
only describes the use of two agents for immediate instillation, the
motivation to use Apaziquone for immediate instillation came from
Appellants’ Specification. Appeal Br. 10. We find this argument
unpersuasive. As discussed above, the recommendation in Oosterlinck is
not limited to the two agents used in the studies referenced but is directed to
using chemotherapeutic agents generally. Nuijen teaches that Apaziquone is
an effective chemotherapeutic agent for treating bladder cancer. FF3. Thus,
the motivation to use Apaziquone stems from the references not from
Appellants’ disclosure.
Claim 2
Appellants argue that claim 2 is separately patentable for the reasons
argued above and because the references do not teach or suggest intravesical
installation as required by claim 2. Appeal Br. 11. We are unpersuaded.
Nuijen specifically teaches intravesical instillation. Nuijen | 5 (“the
compositions of the present invention comprise pharmaceutical products
formulated for intravesical instillation to treat bladder cancer”) and ]fl 2
(“The embodiments of the present invention are directed to compositions for
treating bladder cancer via intravesical instillation. . . . instillation doses
range from. . . .).
Claims 7—10
Appellants contend that claims 7—10 are separately patentable in that
the references do not teach or suggest treating bladder cancer where the
cancer is non-invasive cancer, a transition cell carcinoma, TNM stage Ta or
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Tl, or histologic grade G1 or G2. Appellants’ argument is unpersuasive. As
the Examiner points out, treatment of these types of bladder cancer is
specifically taught by Oosterlinck. Ans. 9—11; Oosterlinck 106 section 3
(referring to treating non-invasive bladder cancer with instillation of a
chemotherapeutic), 106 (disclosing treatment of TNM stage Ta and Tl
lesions and histologic Gl, G2, and G3 tumors), 105—106 (disclosing
immediate instillation of a chemotherapeutic agent after TUR-BT is
encourage in transitional cell carcinoma bladder cancers)..
Claims 11 and 13
In addition to the arguments discussed above, Appellants argue that
claims 11 and 13 are patentable in that the references do not teach the
specific dosage ranges recited in the claims. Appeal Br. 13. We are not
persuaded. The claims recite dosage limits of from 1 to 8 mg (claim 11) and
3 to 5mg (claim 13). Appeal Br. 18 (Claims App’x). These values fall
within the range taught by Nuijen of .5 to 13mg (FF3). Thus, the claimed
ranges are prima facie obvious. In re Peterson, 315 F.3d at 1329.
Claim 16
In addition to the arguments presented above, Appellants argue that
claim 16 is patentable as Nuijen raises doubts about the efficacy of
Apaziquone. Appeal Br. 14. In support of their argument, Appellants cite to
paragraph 4 of Nuijen where the reference discusses failures that have
occurred in clinical trials using Apaziquone. Id. We find this argument
unpersuasive. Once again, we find Appellants have taken a quote out of
context. While Nuijen does note there have been failures to treat some
cancers using systemic delivery of Apaziquone, it points out the failures
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“may be the result of poor drug delivery” to those tumors, rapid plasma
elimination, and poor penetration through multicell layers (Nuijen 14), not
that Apaziquone is ineffective as a general matter. Nuijen states that
“[wjhile these undesirable characteristics are a serious setback for the
treatment of systemic disease,. . . they may be advantageous” for treating
cancers such as superficial bladder cancer. FF2. Nuijen explains that “drug
delivery is not problematical via the intravesical route” for such a “third
compartment cancer” and that, in such cancers, penetration into avascular
tissue “can be increased by maintenance of therapeutically relevant drug
concentrations within the bladder.” Nuijen 14. Moreover, Nuijen goes on
to state that “The results of this study provide strong evidence in support of
the proposal that intravesical administration of E09 may have activity
against bladder tumors.” FF4. Thus, Nuijen sternly encourages the use of
Apaziquone to treat balder cancer. It does not raise doubts about its
efficacy.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner’s conclusion that claims 1, 2, 7—11, 13, and 16 would have been
obvious over Nuijen combined with Oosterlinck and Wientjes.
Claim 3 has not been argued separately and therefore falls with claim
1. 37C.F.R. §41.37(c)(l)(iv).
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IMPROPER DEPENDENT FORM
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that claim 3 is in improper
dependent form.
The Examiner finds that claim 1 calls for the administration of
Apaziquone “immediately after” TUR whereas claim 3 calls for
administration within 6 hours of TUR. Final Act. 3. Using a dictionary
definition, the Examiner defines immediately as not separated in time or
without delay. Id at 4. The Examiner finds that a period of 6 hours later
does not meet either condition and thus is not immediate. Id. Consequently,
the Examiner concludes that claim 3 does not properly depend from claim 1.
Id.
Appellants contend that the Examiner has improperly ignored the
teaching of the Specification where it teaches that immediate means within 6
hours. Appeal Br. 16.
Findings of Fact
FF9. The instant Specification states
This study assessed the tolerability and safety of administering
EOQUIN® immediately (i.g. [sic] within about 6 hours)
following TUR-BT in patients with superficial bladder cancer.
Plasma levels were measured in patients at selected sites to
assess the degree of systemic absorption of EOQUIN®
following intravesical instillation immediately (i.e. within about
6 hours) following TUR-BT.
Spec. 1119.
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Principles of Law
“[T]he specification is always highly relevant to the claim
construction analysis. Usually, it is dispositive; it is the single best guide to
the meaning of a disputed term.” Vitronics Corp. v. Conceptronic, Inc., 90
F.3d 1576, 1582 (Fed. Cir. 1996).
“[DJuring examination proceedings, claims are given their broadest
reasonable interpretation consistent with the specification.” In re Hyatt, 211
F.3d 1367, 1372 (Fed. Cir. 2000).
Analysis
We find that Appellants have the better argument. When read in light
of the Specification, one skilled in the art would understand the term
immediate as used in the claimed method of treating bladder cancer to mean
within 6 hours. The Specification clearly equates immediate administration
of Apaziquone with administration within 6 hours of TUR-BT.
The Examiner contends that since Appellants do not recite a specific
definition of immediate in the Specification, there is no basis for interpreting
the term to embrace delay of up to six hours. Ans. 13—14. We are
unpersauded. The Specification clearly coveys to one skilled in the art that a
period of up to six hours is within the meaning of immediate as used in the
claims. FF9. To hold otherwise would be inconsistent with the teachings of
the Specification.
Conclusion of Law
We conclude that a preponderance of the evidence does not support
the Examiner’s conclusion that claim 3 improperly depends from claim 1.
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SUMMARY
We affirm the rejection under 35 U.S.C. § 103(a).
We reverse the rejection under 35 U.S.C. § 112, fourth paragraph.
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
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