Ex Parte Boccaccio et al

Patent Trial and Appeal Board

Feb 17, 2017

13423830 (P.T.A.B. Feb. 17, 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.
13/423,830 03/19/2012 Carla Boccaccio ES-4636-239 7323
23117 7590 02/22/2017
NIXON & VANDERHYE, PC
901 NORTH GLEBE ROAD, 11TH FLOOR
ARLINGTON, VA 22203
EXAMINER
WU, JULIE ZHEN QIN
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
02/22/2017 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):
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pair_nixon @ firsttofile. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CARLA BOCCACCIO, PAOLO MARIA COMOGLIO,
FIORELLA PETRONZELLI, and RITA DE SANTIS1
Appeal 2015-005635
Application 13/423,830
Technology Center 1600
Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to the use of MET
inhibitors for enhancing the efficacy of radiotherapy in patients suffering
from cancer. The Examiner entered final rejections for obviousness and
nonstatutory obviousness-type double patenting.
We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.
1 Appellants identify the Real Party in Interest as Metheresis Translational
Research SA. Br. 3.
Appeal 2015-005635
Application 13/423,830
STATEMENT OF THE CASE
Background
“The present disclosure concerns the use of MET inhibitors for
enhancing the efficacy of radiotherapy in patients suffering from cancers.”
Spec. 1:5—7.
The Claims
Claims 15—22 and 24—39 are on appeal. Claim 15 is illustrative and
reads as follows:
15. A method of treating a patient suffering from a
tumor comprising:
a) administering to said patient a Met inhibitor, wherein
said Met inhibitor is selected from the group consisting of:
i) DN30 anti-Met monoclonal antibody,
ii) a genetically engineered antibody comprising the six
complementarity determining regions (CDRs) of DN30 anti-
Met monoclonal antibody, said CDRs having the amino acid
sequences set forth in SEQ ID NO.: 12 to 14 and 20 to 22, and
iii) a fragment of (i) or (ii) comprising the six
complementarity determining regions (CDRs) of DN30 anti-
Met monoclonal antibody, said CDRs having the amino acid
sequences set forth in SEQ ID NO.: 12 to 14 and 20 to 22, or
combinations thereof, wherein said DN30 anti-Met monoclonal
antibody is produced by the hybridoma cell line ICLC PD
05006, and
b) subjecting said patient to radiotherapy.
Br. 35 (Claims Appendix).
Independent claim 24 includes the same limitations as claim 15 and
further requires that the Met inhibitor be administered as a nucleotide
sequence encoding the Met inhibitor. Id. at 37.
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Application 13/423,830
Independent claim 38 includes the same limitations as claim 15, but
recites that the method is for enhancing the efficacy of radiotherapy in a
patient being treated for a tumor. Id. at 40.
Independent claim 39 includes the same limitations as claim 38 and
further requires that the Met inhibitor be administered as a nucleotide
sequence encoding the Met inhibitor. Id. at 41.
The Issues
The following rejections are before us to review:
Claims 15—17, 19—22, 24—28, 30-33, 35, 36, 38, and 39 are rejected
under 35 U.S.C. § 103(a) as obvious over Comoglio ’807,2 Morton,3 and
Lai.4 Ans. 2.
Claims 15—17, 19—22, 24—28, 30-33, 35, 36, 38, and 39 are rejected
under 35 U.S.C. § 103(a) as over Comoglio ’807, Morton, and Welsh.5 Ans.
5.
Claims 18, 29, 34, and 37 are rejected under 35 U.S.C. § 103(a) as
obvious over Comoglio ’807, Morton, Lai, and Burgess.6 Ans. 7.
Claims 18, 29, 34, and 37 are rejected under 35 U.S.C. § 103(a) as
obvious over Comoglio ’807, Morton, Welsh, and Burgess. Ans. 9.
2 WO 2007/090807 Al, published Aug. 16, 2007 (“Comoglio ’807”)
3 US 2004/0166544 Al, published Aug. 26, 2004 (“Morton”)
4 Bachchu Lai et al., Targeting the c-METPathway Potentiates
Glioblastoma Responses to y-Radiation, 11(12): Clinical Cancer
Research, 4479-86, (June 15, 2005) (“Lai”)
5 James W. Welsh et al., The c-Met receptor tyrosine kinase inhibitor
MP470 radiosensitizes glioblastoma cells, 4:69 Radiation Oncology, 1—
10 (2009) (“Welsh”)
6 US 2005/0118643 Al, published June 2, 2005 (Burgess”)
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Application 13/423,830
Claims 15—17, 24—28, 33, and 36 are rejected on the ground of
nonstatutory obviousness-type double patenting as obvious over claims 1—7
ofComoglio ’9587. Ans. 12.
Claims 15—17, 24—28, 33, and 36 are rejected on the ground of
nonstatutory obviousness-type double patenting as obvious over claims 31
and 32 of Application No. 13/373,101.8 Ans. 12.
We adopt and incorporate by reference the Examiner’s findings and
conclusions with respect to these references as presented in the Final Action
and Answer. Final Act. 2—169; Ans. 2—26. The findings of fact set forth
below are provided only to highlight certain evidence of record relevant to
our analysis.
FINDINGS OF FACT
FF1. The Specification teaches “[t]he aminoacid sequences
corresponding to DN30 heavy chain CDR regions are the following: CDR-
Hl: GYTFTSYW (SEQ ID NO.: 12); CDR-H2: INPSSGRT (SEQ ID
NO.: 13); CDR-H3: ASRGY (SEQ ID NO.: 14). Spec. 15:29-32.
FF2. The Specification teaches “[t]he aminoacid sequences
corresponding to DN30 light chain CDR regions are the following: CDR-F1:
QSVDYDGGSY (SEQ ID N0.:20); CDR-F2: AAS (SEQ ID NO.:21); CDR-
L3: QQSYEDPLT (SEQ ID NO. :22). Spec. 16:6-9.
FF3. Comoglio ’807 teaches use of “an anti-Met monoclonal
antibody” or “a genetically engineered antibody containing the epitope
7 US 8,388,958 B2, issued Mar. 5, 2013 (“Comoglio ’958”)
8 The application issued as US 8,729,043 B2 on May 20, 2014.
9 Final Action, mailed April 24, 2014
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Application 13/423,830
binding region or the complementary determining regions (CDRs) of an
anti-Met monoclonal antibody for the preparation of a medicament for the
treatment of tumors and metastases in a subject suffering from a tumor.”
Comoglio ’807 3:6—22.
FF4. Comoglio ’807 teaches “use of a vector comprising at least a
portion of the nucleotide sequence encoding for the epitope binding region
or the CDRs of the anti-Met monoclonal antibody produced by the
hybridoma cell line ICLC PD 05006 for the preparation of a medicament for
the treatment of tumors and metastases in a subject affected by a tumor.”
Comoglio ’807 3:23-29.
FF5. Comoglio ’807 teaches the “aminoacid sequences corresponding
to the CDRregions are . . . CDR-H1: GYTFTSYW (SEQ ID NO.:8); CDR-
H2: INPSSGRT (SEQ ID NO.:9); CDR-H3: ASRGY (SEQ ID NO.: 10). . .
CDR-L1: QSVDYDGGSY (SEQ ID NO.: 11); CDR-L2: AAS (SEQ ID
NO.: 12); CDR-L3: QQSYEDPLT (SEQ ID NO.: 13).” Comoglio ’807
22:23-23:1.
FF6. Comoglio ’807 teaches “the use of a vector comprising at least
a portion of the nucleotide sequence encoding for the epitope binding region
or the CDRs of the anti-Met monoclonal antibody produced by the
hybridoma cell line ICLC PD 05006 for the preparation of a medicament for
the treatment of tumors and metastases in a subject affected by a tumor.”
Comoglio ’807 3:23-29.
FF7. Morton teaches co-administration of an antibody with an
additional therapeutic agent or as “combination therapy” in which
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Application 13/423,830
“administration of the c-Met antibody may be administered prior to or
subsequent to other therapy, such as radiotherapy.” Morton 1273.
FF8. Lai teaches that reduction in c-Met expression leads to increased
sensitivity to radiation therapy. Specifically, Lai manipulated“[e]ndogenous
expression of SF/HGF and c-Met was targeted in U87 MG human malignant
glioma cells and xenografts using chimeric Ul/ribozymes . . . Ul/ribozymes
knocked down SF/HGF and c-Met mRNA and protein levels, sensitized cells
to y-radiation (P < 0.005), and enhanced radiation-induced caspase-
dependent cytotoxicity in vitro (P < 0.005). . . Targeting the SF/HGF/c-Met
pathway markedly potentiates the antiglioma response to y-radiation.” Lai
Abstract.
FF9. Welsh teaches
The small-molecule tyrosine kinase inhibitor MP470 was
designed to target c-Met... To evaluate its effect on
proliferation eight GEM cell lines were used in an MTS assay.
All eight cell lines proved to be sensitive to MP470 alone, with
IC50 values ranging from 1 /uM to 10 /uM (median 5 /uM). To
test its potential as a radiosensitizer, we assessed clonogenic
survival after 4 Gy of the same eight GEM cell lines after a 1-
hour treatment with MP470 followed by a single radiation dose
(Fig. 1). Various levels of response were seen in the different
cell lines, with 3 of the 8 GEM lines appearing to have a greater
then additive response when MP470 was combined with XRT.
SF767 cells were chosen to assesses for clonogenic survival in
response to increasing doses of radiation (0 to 8 Gy) and
MP470 had a radio sensitizing effect at all radiation doses
tested, MP470 increased cell kill by 0.5 log compared to 4 Gy
alone (Fig. 2).
Welsh 4—5.
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Application 13/423,830
FF10. Welsh teaches
In order to confirm MP470’s mechanism of action we evaluated
a known downstream pathway of cMet, phosphatidylinositol 3-
kinase/Akt, in SF767 cells . . . MP470 alone had no effect on
cell death, and radiation alone induced a mild increase in cell
death (this stands in contrast to the percent of death seen in a
clonogenic assay, since the majority of radiation induced cell
death is from mitotic division and not apoptotic). The
combination of MP470 followed by radiation (8 Gy), however,
killed 75% of the cells.
Welsh 5.
FF11. Comoglio ’958 teaches the “nucleotidic and am[]inoacid
sequences corresponding to the CDR regions are [provided]; their
am[]inoacid sequences are: CDR-H1: GYTFTSYW (SEQ ID NO.:8); CDR-
H2: INPSSGRT (SEQ ID NO.:9); CDR-H3: ASRGY(SEQ ID NO.:10). . .
CDR-L1: QSVDYDGGSY (SEQ ID NO.: 11); CDR-L2: AAS (SEQ ID
NO.: 12); CDR-L3: QQSYEDPLT (SEQ ID NO.: 13).” Comoglio ’958
11:29-41.
FF12. Comoglio ’043 teaches the “nucleotidic and am[]inoacid
sequences corresponding to the CDR regions are [provided]; their
am[]inoacid sequences are: CDR-H1: GYTFTSYW (SEQ ID NO.:8);
CDR-H2: INPSSGRT (SEQ ID NO.:9); CDR-H3: ASRGY(SEQ ID NO.: 10)
. . . CDR-L1: QSVDYDGGSY (SEQ ID NO.:l 1); CDR-L2: AAS (SEQ ID
NO.: 12); CDR-L3: QQSYEDPLT (SEQ ID NO.: 13).” Comoglio ’043
11:29-41.
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Application 13/423,830
OBVIOUSNESS
The Examiner has set forth a prima facie case that the claims would
have been obvious over the cited prior art combination(s). We address
Appellants’ arguments below.
Rejection over Comoglio ’807, Morton, and Lai
Appellants argue that Comoglio ’807 “does not teach a method of
treating tumors comprising the use of MET inhibitors and radiotherapy,”
Morton “is silent to the particular antibody of the present invention, DN30,
and additionally is silent to the specific engineered antibodies, antibody
fragments and in particular cell-line (ICLC PD 05006) used to produce the
DN30 of the present invention,” and that Lai “at most discloses an siRNA
(ribozyme) inhibitor of HGF and c-MET that reduces resistance to
radiotherapy and goes on to suggest that other inhibitors of c-MET
activation could be useful in reducing or preventing a subject’s resistance to
radiotherapy.” Br. 13—14. According to Appellants, “nothing in the cited art
would have provided basis for a reasonable expectation of success.” Id. at
14.
Appellants’ arguments are unpersuasive as the Examiner’s rejection is
based on the combined teachings of Comoglio ’807, Morton, and Lai. See
Ans. 2—5. Nonobviousness cannot be established by attacking the references
individually when the rejection is predicated upon a combination of prior art
disclosures. In re Merck & Co. Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986);
see also In re Keller, 642 F.2d 413, 426 (CCPA 1981) (finding “one cannot
show nonobviousness by attacking references individually where, as here,
the rejections are based on combinations of references” (citations omitted)).
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Thus, whether Comoglio ’807, Morton, or Lai individually fails to teach
treating a tumor patient by administering the claimed antibody or
complementary determining regions (CDRs) and subjecting the patient to
radiotherapy is not dispositive. As stated by the Examiner, Comoglio ’807
teaches use of an anti-Met monoclonal antibody or a genetically engineered
antibody containing the CDRs in the preparation of a treatment for tumors.
FF3; Ans. 3. The nucleotide and amino acid sequences provided in
Comoglio ’807 for the CDR regions are identical to those provided for the
DN30 CDR regions. FF5; Ans. 3. (