Ex Parte Klingemann

Patent Trial and Appeal Board

Oct 24, 2013

10008955 (P.T.A.B. Oct. 24, 2013)

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.
10/008,955 12/07/2001 Hans Klingemann 105910-0452 5420
30542 7590 10/25/2013
FOLEY & LARDNER LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
EXAMINER
SCHWADRON, RONALD B
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
10/25/2013 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 PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HANS KLINGEMANN1
__________

Appeal 2012-003936
Application 10/008,955
Technology Center 1600
__________

Before LORA M. GREEN, MELANIE L. McCOLLUM, and
ANNETTE R. REIMERS, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a cancer
treatment method. The Examiner has rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.

1 Appellant identifies the real party in interest as Conkwest, Inc. (App.
Br. 1).
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Application 10/008,955

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STATEMENT OF THE CASE
Claims 20, 26, 27, and 30 are on appeal (App. Br. 1).2 Claim 20 is
illustrative and reads as follows:
20. A method of treating a cancer in vivo in a mammal comprising
the step of administering to the mammal a medium comprising an NK-92
cell line ATCC Deposit No. CRL-2407, wherein said cancer is recognized
and lysed by said NK-92 cell line.
Claims 20, 26, 27, and 30 stand rejected under 35 U.S.C. § 103(a) as
obvious over Gong3 in view of Santoli4 (Ans. 5).5
The Examiner relies on Gong for teaching the “use of NK-92 cells to
lyse leukemic tumor cells” (id.). The Examiner relies on Santoli for
teaching “that lytic human derived cell lines can be used in vivo to treat
disease/cancer or in preclinical in vivo studies” (id.). The Examiner
concludes that it would have been prima facie obvious, in view of Gong and
Santoli, to have created the claimed invention in order to use NK-92 cells
“in vivo to treat disease or in preclinical in vivo studies” (id. at 6).

2 Claims 1-19, 21, 23-25, 28, 29, and 31 are also pending but have been
withdrawn from consideration (App. Br. 1).
3 Gong et al., Characterization of a Human Cell Line (NK-92) with
Phenotypical and Functional Characteristics of Activated Natural Killer
Cells, 8 LEUKEMIA 652-658 (1994).
4 Santoli et al., US 5,272,082, Dec. 21, 1993.
5 Claims 20, 26, 27, and 30 also stand provisionally rejected on the ground
of nonstatutory obviousness-type double patenting over claims 30-35, 46,
48, 50, and 53 of copending Application No. 10/701,359 (Ans. 4-5).
However, an Express Abandonment has been filed in Application
No. 10/701,359, rendering the rejection moot.
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Application 10/008,955

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ANALYSIS
Santoli relates “to genetically modified cytotoxic T lymphoblastic
leukemia cell lines (T-ALL)” (Santoli, col. 1, ll. 11-13). In particular,
Santoli discloses two leukemia T cells lines designated TALL-104 and
TALL-107 (id. at col. 2, ll. 41-43). Santoli also discloses that the “cell lines
may be used in a therapeutic regimen in the treatment of cancers” (id. at
col. 10, ll. 9-11). In addition, Santoli discloses that “it is preferred that the
method of this invention be performed in vivo by administering directly to
the patient the modified cytotoxic T cell line” (id. at col. 10, ll. 43-45).
Gong discloses:
Figure 4 summarizes the results of 51CR-release assays using
NK-92 cells as effectors against different human leukemic
target cell lines. NK-92 cells spontaneously kill K562
[erythroleukemia] and Daudi [Burkitt lymphoma] cells with
high efficiency. Even at low E : T [effector : target] cell ratio
of 1 : 1, 83% of K562 cells and 76% of Daudi cells were killed
by NK-92 cells, whereas cytotoxicity against TF-1 cells (23%)
and AML-193 cells (6%), was lower.
(Gong 653-654.) We conclude that the Examiner has set forth a prima facie
case that it would have been obvious to administer NK-92 in vivo to a
mammal to treat cancer.
Appellant argues, however, that “the Examiner has failed to provide
any evidence of a suggestion or motivation in Gong et al. or Santoli et al. or
from generally available knowledge that would have led one skilled in the
art to combine the teachings of Gong et al. and Santoli et al.” (App. Br. 11).
We are not persuaded.
We understand Appellant’s argument that “Santoli et al.’s teaching is
limited to T-ALL cell lines” and that there “is nothing in Santoli et al. to
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suggest that the teachings therein may be extended to any other cell lines”
(App. Br. 11). However, as noted by the Examiner (Ans. 5), Gong discloses
that “NK-92 cells spontaneously kill K562 [erythroleukemia] and Daudi
[Burkitt lymphoma] cells with high efficiency” (Gong 653-654). As also
noted by the Examiner (Ans. 8-9), the Specification discloses that
“[a]ctivated and expanded (i.e., cultured to proliferate) NK cells . . . have
been used in . . . in vivo treatment in patients with advanced cancer”
(Spec. 2: 24-26). Thus, we conclude that the evidence supports the
Examiner’s conclusion that one of ordinary skill in the art would have had
reason to administer Gong’s cytotoxic cell line by the in vivo method
disclosed in Santoli (Ans. 7-8).
We note Appellant’s reliance on the Klingemann Declaration,6 which
states that “there is no teaching, suggestion, or motivation in Gong et al. that
would lead one skilled in the art to use the NK-92 cell line in vivo to lyse
tumor cells or as a cancer treatment, much less successfully reduce such a
use to practice as a method of treating mammals” (Decl. 7, ¶ 24c).
However, “Appellant’s opinion on the ultimate legal issue is not evidence in
the case.” In re Lindell, 385 F.2d 453, 456 (CCPA 1967). In addition, we
conclude that Appellant has not provided adequate reasoning to persuasively
support this statement. See id.
Appellant also argues that there was not a reasonable expectation that
the claimed method would be successful (App. Br. 20). In particular,
Appellant relies on the Klingemann Declaration, which states that “[m]ost
certainly one skilled in the art would not have had a reasonable expectation

6 Declaration of Hans Klingemann, M.D., Ph.D., submitted Oct. 15, 2008.
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of success” (Decl. 11, ¶ 30). However, we conclude that this statement is
not persuasively supported by the evidence of record.
In particular, Appellant argues that there was no reasonable
expectation for success “because even the inventor did not initially
recognize the importance or utility of the NK-92 cells in a clinical setting”
(App. Br. 20). However, we do not agree that Appellant’s failure to
“recognize the importance or utility of the NK-92 cell line in a clinical
setting” (Decl. 7, ¶ 24c) demonstrates that one of ordinary skill in the art,
who was aware of the disclosures of both Gong and Santoli,7 would fail to
recognize the potential importance of the NK-92 cell line in a clinical
setting, nor do we agree with Appellant that this demonstrates that there
would not have been a reasonable expectation for success.
In addition, Appellant notes in the Declaration:
[K]now-how with respect to one cell line cannot automatically
be transferred or applied to another cell line, even where the
cells are closely related, including with respect to culture
conditions, requirements for growth factors such as IL-2,
survival and signaling patterns following adoptive transfer,
ability to migrate to tumor sites, sensitivity to chemotherapeutic
agents, response to staining with vital dyes, ability to maintain
their cytotoxic activity following radiation, and susceptibility to
gene transfer.
(Decl. 7-8, ¶ 27.)

7 Appellant acknowledges that he “was not aware of Santoli et al.’s T-ALL
cell lines at the time that [he] created the unmodified NK-92 cell line . . .
disclosed in Gong et al. or at the time that [he] arrived at the method of
treating a pathology in vivo in a mammal by administering NK-92 cells”
(Decl. 7, ¶ 26).
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However, we are not relying on Santoli to teach culture conditions,
requirements for growth factors such as IL-2, survival and signaling patterns
following adoptive transfer, sensitivity to chemotherapeutic agents, response
to staining with vital dyes, ability to maintain their cytotoxic activity
following radiation, or susceptibility to gene transfer. With regard to the
ability to migrate to tumor sites, we conclude that Appellant has not
adequately explained why there would not have been a reasonable
expectation that Gong’s cell line would migrate to tumor sites.
Appellant also states in the Declaration that, “[i]f one skilled in the art
were to have applied the teachings of Santoli et al to the NK-92 cells
disclosed in Gong et al, they would not have had successful results because
of the unique characteristics and requirements of these cells” (Decl. 11,
¶ 30). However, as discussed above, we do not agree that the Examiner is
applying, for example, the culture conditions of Santoli to the NK-92 cells.
Instead, Santoli is being relied upon to teach in vivo administration (Ans. 5).
We conclude that the Appellant has not adequately explained why in vivo
administration, as disclosed in Santoli, of NK-92 cells “would not have
[provided] successful results” (Decl. 11, ¶ 30), nor has Appellant adequately
explained why in vivo administration of NK-92 cells would not have been
reasonably expected to provide successful results.
Moreover, we do not agree that Appellant has provided sufficient
evidence of secondary considerations to overcome the prima facie case of
obviousness. In particular, Appellant argues:
Applicant recognized in the ‘955 application that “[t]here thus
remains a need for a method of treating a pathology related to
cancer or a viral infection with a natural killer cell line that
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maintains viability and therapeutic effectiveness against a
variety of tumor classes.” See ‘955 Application, 4:24-26. The
Examiner has failed to recognize or consider that Applicant’s
claimed method, as set forth in claim 20, meets this need.
(App. Br. 27.) However, “long-felt need is analyzed as of the date of an
articulated identified problem and evidence of efforts to solve that problem.”
Texas Instruments, Inc. v. Int’l Trade Comm’n, 988 F.2d 1165, 1178 (Fed.
Cir. 1993). Appellant has not provided sufficient objective evidence that the
method of claim 20 solves a long-felt but unresolved need.
Appellant also argues that “data disclosed in the ‘955 Application
demonstrate that NK-92 cells are more cytolytic than T-ALL 104 cells or
YT cells” (App. Br. 28). Specifically, Appellant relies on the data set forth
in Examples 9, 10, and 14 of the Specification (id.). We note initially that
Examples 9 and 10 are both directed to in vitro data. However, Gong
teaches that, in vitro, “NK-92 cells spontaneously kill K562 and Daudi cells
with high efficiency” (Gong 654). In addition, “[m]ere recognition of latent
properties in the prior art does not render nonobvious an otherwise known
invention.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir.
1991). Thus, we agree with the Examiner that evidence that NK-92 cells are
more cytolytic in vitro than TALL-104 cells or YT cells is insufficient to
demonstrate that the present method provides an unexpected result
(Ans. 17).
Example 14 does provide some in vivo data, the results of which are
depicted in Figure 9B (Spec. 11: 1-9, & 44: 1-28). In addition, this data does
show a decreased surface area of leukemic cells 10 weeks post-inoculation
with NK-92 as compared to TALL-104 (id. at Fig. 9B). However, Appellant
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has not provided sufficient evidence that this difference is unexpected,
particularly in view of the in vitro data indicating that NK-92 cells are more
cytolytic than TALL-104 cells.
Claim 26 depends from claim 20 and recites that “the route of
administration of the cells to the mammal is intravenous and the mammal is
human.” Appellant argues:
The Examiner here has provided no such “articulated
reasoning” to support his finding that dependent claim 26 is
obvious. Any teaching in Santoli et al. with respect to
intravenous injection is rendered moot because, as discussed
above, the Examiner has failed to articulate the reasons why
one skilled in the art would look to the teachings of Santoli et
al. as a teaching with respect to a method of treating cancer
comprising the step of administering the NK-92 cell line.
(App. Br. 35.) We are not persuaded.
As noted by the Examiner (Ans. 5), Santoli discloses that, “[f]or
human patients, the T-ALL cells may be injected intravenously (i.v.)”
(Santoli, col. 10, ll. 52-54). In addition, we conclude that Appellant has not
adequately explained why one of ordinary skill in the art would not look to
Santoli to teach how to inject cytotoxic cells into a human.
Claim 27 depends from claim 20 and recites that the method further
comprises “administering to said mammal a cytokine that promotes the
growth of said NK-92 cell line.” Appellant argues:
Santoli et al. do not teach that T-ALL cells “can be
administered with the cytokine IL-2.” . . . Rather, Santoli et al.
teach “incorporating into the cell line a selected lymphokine
gene.” . . . Incorporation of a gene into the cell line is simply
not a teaching of “administering to the mammal a cytokine that
promotes the growth of the NK-92 cell line,” as is claimed in
Applicant’s dependent claim 27. Accordingly, the Examiner
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has again failed to articulate the reasons why one skilled in the
art would look to the teachings of Santoli et al. as a teaching
with respect to the NK-92 cell line.
(App. Br. 36.) We are not persuaded.
As noted by the Examiner (Ans. 5), Gong discloses that
“[p]roliferation of NK-92 cells is strongly dependent on the presence of
IL-2” (Gong 658). In addition, Gong discloses that “NK and A-NK
[activated NK] cells have been utilized in several clinical trials in cancer
patients, mostly in conjunction with IL-2” (id. at 652). Thus, we agree with
the Examiner that it would have been obvious to administer NK-92 cells
with IL-2.
Claim 30 depends from claim 20 and recites that “the cancer is a solid
tumor.” Appellant argues that “the Examiner has failed to provide ‘some
articulated reasoning with some rational underpinning to support the legal
conclusion of obviousness’” (App. Br. 37). We agree.
The Examiner finds that Santoli teaches that its “cells can be modified
to bind solid tumors” (Ans. 6). However, we conclude that the Examiner
has not set forth a prima facie case that it would have been obvious to use
NK-92 cells to treat solid tumors, as Gong uses the NK-92 cells to kill
erythroleukemia and Burkitt lymphoma cells.
CONCLUSION
The evidence supports the Examiner’s conclusion that Gong and
Santoli suggest the methods of claims 20, 26, and 27. We therefore affirm
the obviousness rejection of claims 20, 26, and 27.
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However, the Examiner has not set forth a prima facie case that Gong
and Santoli suggest the method of claim 30. We therefore reverse the
obviousness rejection of claim 30.
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-IN-PART

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