Ex Parte Santin et al

Board of Patent Appeals and Interferences

Jan 24, 2012

11248702 (B.P.A.I. Jan. 24, 2012)

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.
11/248,702 10/12/2005 Alessandro D. Santin Y03-130US 1595
28156 7590 01/25/2012
COLEMAN SUDOL SAPONE, P.C.
714 COLORADO AVENUE
BRIDGE PORT, CT 06605-1601
EXAMINER
GODDARD, LAURA B
ART UNIT PAPER NUMBER
1642
MAIL DATE DELIVERY MODE
01/25/2012 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ALESSANDRO D. SANTIN and FABRIZIO COMPER
__________

Appeal 2010-012332
Application 11/248,702
Technology Center 1600
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and
STEPHEN WALSH, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON REQUEST FOR REHEARING
Appellants request rehearing of our Decision dated September 15,
2011. We have jurisdiction under 35 U.S.C. § 6(b).
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STATEMENT OF THE CASE
The following claims are representative and read as follows:
1. A method of treating cancer in a human comprising:
administering to the human a therapeutically effective amount of
Clostridium perfringens enterotoxin (CPE) or a pharmaceutically effective
salt thereof;
wherein the cancer is ovarian serous papillary carcinoma, ovarian
clear cell carcinoma, or uterine serous papillary carcinoma;
wherein the CPE is native CPE (SEQ ID NO:1) or a variant thereof
comprising a sequence at least 90% identical to residues 45-319 of SEQ ID
NO:1;
wherein the CPE or pharmaceutically acceptable salt thereof is
administered intravenously or intraperitoneally.

2. The method of claim 1, wherein the cancer includes chemotherapy-
resistant malignant cells and chemotherapy-sensitive malignant cells, and the
CPE preferentially binds to chemotherapy-resistant malignant cells over
chemotherapy-sensitive malignant cells.

3. The method of claim 1 wherein the cancer includes metastatic malignant
cells and primary tumor malignant cells, and the CPE preferentially binds to
metastatic malignant cells over primary tumor cells.

5. The method of claim 1 wherein the cancer is uterine serous papillary
carcinoma.

10. The method of claim 1 further comprising administering a protective
agent that protects cells against CPE toxicity;
wherein the protective agent comprises residues 290-319 of SEQ ID
NO:1 or a fragment thereof that binds specifically to claudin-3 and/or
claudin-4.

12. A method of treating cancer in a human comprising:
intraperitoneally administering to the human a therapeutically
effective amount of Clostridium perfringens enterotoxin (CPE) or a
pharmaceutically acceptable salt thereof,
wherein at least some cancerous cells are located in or adjacent to the
peritoneal cavity of the human, and the cells are sensitive to CPE;
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wherein the CPE is native CPE (SEQ ID NO:1) or a variant thereof
comprising a sequence at least 90% identical to residues 45-319 of SEQ ID
NO:1.

13. The method of claim 12 wherein the cancerous cells include
chemotherapy-resistant cells and chemotherapy-sensitive cells, and the CPE
preferentially binds to chemotherapy-resistant cancerous cells over
chemotherapy-sensitive cancerous cells.

40. The method of claim 12 further comprising administering a
protective agent that protects cells against CPE toxicity;
wherein the protective agent comprises residues 290-319 of SEQ ID
NO: l or a fragment thereof that binds specifically to claudin-3 and/or
claudin-4.

42. The method of claim 41 wherein the cancer includes
chemotherapy-resistant malignant cells and chemotherapy-sensitive
malignant cells, and the CPE preferentially binds to chemotherapy-resistant
malignant cells over chemotherapy-sensitive malignant cells.

43. The method of claim 41 wherein the cancer is a recurrent cancer.

45. The method of claim 12 wherein the cancer is a recurrent cancer.

46. The method of claim 2 wherein the CPE comprises residues 45-
319 of SEQ ID NO: l.

Additional References Cited

American Cancer Society – How is Ovarian Cancer Treated?
http://www.cancer.org/docrootfCRIIcontentfCRC2_2_4X_ ...
an_Cancer_Treated_33.asp?sitearea=CRI&viewmode -5 pages printed April
24, 2010.

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Look et al., Long-term results of cytoreductive surgery for advanced and
recurrent epithelial ovarian cancers and papillary serous carcinoma of the
peritoneum, 14 Int. J. Gynecol Cancer 35-41 (2004).

Huh et al., Uterine papillary serous carcinoma: comparisons of outcomes in
surgical Stage I patients with and without adjuvant therapy, 91 Gynecologic
Oncology 470-475 (2003).

Grounds of Rejection on Rehearing
3. Claims 12-15, 17, 38, 39, 44 and 45 are rejected under 35 U.S.C. §
103(a) over Sukumar,
1
in view of Redlich
2
and Pusztai.
3

4. Claims 1-4, 6-9, 16, 37, 41-43 and 46 are rejected under 35 U.S.C. §
103(a) over Sukumar, in view of Redlich, Pusztai, Hibbs,
4
and Hough.
5

Discussion
3. Claims 12-15, 17, 38, 39, 44 and 45 are rejected under 35 U.S.C. §
103(a) over Sukumar, in view of Redlich and Pusztai.

1
Sukumar et al., WO 03/069307 A2, published August 21, 2003.
2
Redlich et al., Clostridium difficile Toxin A Therapy for HCT 116 Human
Colon Cancer in Nude Mice, 57 Journal of Surgical Oncology 191-195
(1994).
3
Pusztai et al., Physiologic and Pathologic Drug Resistance in Ovarian
Carcinoma, 37 Acta Oncologica 629- 640 (1998).
4
Hibbs et al., Differential Gene Expression in Ovarian Carcinoma, 165
American Journal of Pathology 397- 414 (2004).
5
Hough et al., Large-Scale Serial Analysis of Gene Expression Reveals
Genes Differentially Expressed in Ovarian Cancer, 60 Cancer Research
6281-6287 (2000).
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ISSUE
Appellants contend that the Board did not correctly consider evidence
of nonobviousness and Appellants‟ arguments of unexpected results. (Req.
Reh‟g. 8.) With respect to Rejection 3, Appellants separately argued claims
13 and 45 in the Brief, pages 17 and 20.
Appellants argue that they pointed to unexpected results throughout
the Brief, particularly that the recurrent and metastatic tumors and
chemotherapy resistant-tumors each have more claudin 3 and claudin 4
receptors than nonrecurrent tumors, or primary tumors, or chemotherapy-
sensitive tumors in ovarian serous papillary carcinoma. (See Specification
page 60, first and second full paragraphs and Figures 7 and 8.) Thus, “CPE
preferentially binds to chemotherapy-resistant malignant cells over
chemotherapy-sensitive malignant cells” as is recited in claims 2, 13, and 46,
“CPE preferentially binds to metastatic malignant cells over primary tumor
malignant cells” as is recited in claim 3, and CPE is unusually suited to treat
recurrent cancer, as is recited in claims 4,43, and 45. This means one would
expect that CPE is actually more effective at killing metastatic malignant
cells than primary tumor cells, is more effective against chemotherapy-
resistant cells than chemotherapy-sensitive cells, and is more effective
against recurrent cancers than against nonrecurrent cancers. That expectation
is confirmed by the data in Figure 9 of the Specification, discussed in the
paragraph bridging pages 61-62, showing that “The cytotoxic effect was
dose dependent and was positively correlated to the levels of either claudin-3
or claudin-4 expression as tested by RT-PCR in tumor samples.” These are
wonderful results. These are exactly the most difficult cancers to treat, and
yet CPE is more effective against these cancers - metastatic, recurrent, and
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chemotherapy resistant –than against the easier to treat primary, non-
recurrent, and chemotherapy sensitive cancers. Nothing in the prior art
suggests this, and the Board has not alleged that it does. (Req. Reh‟g. 8-9.)
The issue is: Did the Board overlook Appellants‟ evidence of
unexpected results?

ANALYSIS

Appellants contend that the Board did not correctly consider evidence
of nonobviousness and Appellants‟ arguments of unexpected results. (Req.
Reh‟g. 8.) We find Appellants‟ argument unconvincing. To begin, the
Decision page 12, adopted the Examiner‟s responses to Appellants‟
arguments set forth in the Answer. The Answer addressed Appellants‟
arguments of unexpected results in numerous locations. Moreover, the
Decision pages 13-14 further addressed Appellants‟ evidence of unexpected
results.
With respect to claim 12, we stand by our original decision and are
not persuaded by Appellants‟ evidence of unexpected results.
Claim 12 is not limited to a particular type of cancer but does require
the CPE to be administered intraperitoneally. Importantly, claim 12 is not
limited to cancer including chemotherapy-resistant malignant cells and
chemotherapy-sensitive malignant cells, and the CPE preferentially binds to
chemotherapy-resistant malignant cells over chemotherapy-sensitive
malignant cells; ovarian serous papillary carcinoma; or recurrent cancer.
These are the limitations which Appellants argue are supported by
unexpected results. (See Req. Reh‟g. 8.) Further, on page 11 of the Request
for Rehearing Appellants argue that claim13 regarding chemotherapy
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resistant cells and intraperitoneal injection, but provide no evidence of
unexpected results with respect to the scope of claim 12, which is not so
limited.
Sukumar treats breast cancer cells known to express claudins 3 and 4
and mentions that CPE can also be used to treat ovarian cancer. “„If a
reference's disclosure relates to the same problem as the claimed invention,
“that fact supports use of that reference in an obviousness rejection.‟” In re
Clay, 966 F.2d 656, 659 Cir. 1992).” Princeton Biochemicals Inc. v.
Beckman Coulter Inc., 411 F.3d 1332 (Fed. Cir. 2005). Sukumar indicates
that CPE can be administered by several means known to those of ordinary
skill in the art. (See Sukumar 13.) Intraperitoneal injection is a method of
administration known to those of ordinary skill in the art. Redlich further
supports that it is conventional, and known to those of ordinary skill in the
art to administer bacterial toxins intraperitoneally. Thus, in view of
Sukumar and Redlich, one of ordinary skill in the art would have expected a
benefit associated with the treatment of cancer known to express claudins 3
and 4 with CPE by any mode of administration. Appellants have come forth
with no comparative evidence showing unexpected results to show
otherwise, for the scope of claim 12.
With respect to claim 13, Appellants argue that they treated a more
dangerous cancer, ovarian serous papillary carcinoma and achieved better
results. Claim 13 is not limited to ovarian serous papillary carcinoma.
Appellants argue that Sukumar achieved a reduction in tumor volume but
not extension of life. (Req. Reh‟g. 11-12.) This statement is unsupported by
the evidence of record. While Sukumar does not indicate extension of life
occurred, it does not indicate that extension of life did not occur. Appellants
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have come forth with no evidence to show that Sukumar did not achieve
extension of life, and therefore Appellants‟ alleged extension of life
unexpected result is inconclusive. No comparative data is presented by
Appellants.
With respect to the chemotherapy-resistant cells of claim 13, the
Examiner provided evidence that the ovarian cancer cells of Sukumar
included chemotherapy resistant and chemotherapy sensitive cells in view of
Pusztai. (See Ans. 43.) Appellants have provided no evidence of unexpected
results comparing the treatment of ovarian cancer cells of Sukumar, or
showing that the cells of Sukumar do not include chemotherapy resistant and
chemotherapy sensitive cells.
With respect to claim 45, the Examiner found that the Specification
page 60 evidenced that recurrent cancer is the same as chemotherapy
resistant cancer. (See Ans. 53.) Appellants do not dispute this finding. As
argued with respect to claim 13, Appellants have provided no evidence of
unexpected results or long-felt need comparing the treatment of the ovarian
cancer cells of Sukumar which include chemotherapy resistant cells and thus
are recurrent cancer cells.
Appellants argue that inherency does not apply to an obviousness
rejection. However, the express, implicit, and inherent disclosures of a prior
art reference may be relied upon in the rejection of claims under 35 U.S.C.
102 or 103. “The inherent teaching of a prior art reference, a question of
fact, arises both in the context of anticipation and obviousness.” In re
Napier, 55 F.3d 610, 613 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103
rejection based in part on inherent disclosure in one of the references).
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We have therefore, considered Appellants‟ unexpected results and
long-felt need and have found them unconvincing on the evidence before us.
For the reasons indicated in the Decision, the evidence of long-felt need is
not persuasive. The request for reconsideration is denied.

4. Claims 1-4, 6-9, 16, 37, 41-43 and 46 are rejected under 35 U.S.C.
§ 103(a) over Sukumar, in view of Redlich, Pusztai, Hibbs, and Hough.
Appellants separately addressed claims 2, 3, and 5 in the Brief, pages
21-22, and claim 4 in the Reply Br. 11.
With respect to claims 2 and 3, the Examiner found that the prior art
treated with the instantly claim CPE and thus would inherently be expected
to preferentially bind to chemotherapy resistant malignant cells and
metastatic malignant cells. Appellants provided no evidence that the CPE
claimed differs from the prior art CPE and its ability to preferentially bind to
chemotherapy resistant malignant cells and metastatic malignant cells.
The Examiner addressed Appellants‟ arguments with respect to claims
2, 5, 42, 43 and 46 on pages 56-58 of the Answer, which we adopted in the
Decision. We stand by our original Decision with respect to these claims.

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CONCLUSION OF LAW
The request for rehearing is denied and we stand behind our original
decision.
DENIED

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