Ex Parte Chokri et al

Board of Patent Appeals and Interferences

Jun 18, 2009

10195065 (B.P.A.I. Jun. 18, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_________________

Ex parte MOHAMED CHOKRI, JACQUES BARTHOLEYNS,
and JEAN-LOUP ROMET-LEMONNE

Appellants
_________________

Appeal 2009-001302
Application 10/195,065
Technology Center 1600
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Decided1: June 19, 2009
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Before RICHARD TORCZON, SALLY GARDNER LANE, and
MICHAEL P. TIERNEY, Administrative Patent Judges.

LANE, Administrative Patent Judge.

DECISION ON APPEAL

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

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I. STATEMENT OF THE CASE
The appeal, under 35 U.S.C. § 134, is from a Final Rejection of claims
23-31. Claims 1-22 were cancelled. (App. Br. 12). We affirm.
Appellants claim a method of isolating mononuclear cells and
culturing them in IL2-13 and GM-CSF3 to obtain differentiated monocyte-
derived antigen presenting cells (“MD-APCs”).
The Examiner relied on the following references:
• Chokri et al., “Production of Human Macrophages with Potent
Antitumor Properties (MAK) by Culture of Monocytes in the
Presence of GM-CSF and 1,25-Dihydroxy Vitamin D3,” 12
Anticancer Res. 2257-60 (1992) (“Chokri”).
• Jacobsen et al., “Interleukin 13: Novel Role in Direct
Regulation of Proliferation and Differentiation of Primitive
Hematopoietic Progenitor Cells,” 180 J. Exp. Med. 75-82
(1994) (“Jacobsen”).
The Examiner rejected claims 23-31 under 35 U.S.C. § 103(a) over
Chokri and Jacobsen. Appellants did not argue for the separate patentability
of any of the claims. We focus on claim 23 as a representative claim. See
37 C.F.R. § 41.37(c)(1)(vii).
The Examiner also rejected claims 23-31 under 35 U.S.C. § 112, first
paragraph, for lack of a written description to support certain elements in
these claims.

2 Interleukin.
3 Granulocyte/macrophage colony stimulating factor.
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II. LEGAL ANALYSIS
“When there is a design need or market pressure to solve a problem
and there are a finite number of identified, predictable solutions, a person of
ordinary skill has good reason to pursue the known options within his or her
technical grasp. If this leads to the anticipated success, it is likely the
product not of innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might show that it
was obvious under § 103.” KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 421
(2007).
III. FINDINGS OF FACT
1. Appellants’ claim 23 recites4:
A method of preparing monocyte-derived antigen presenting
cells (MD-APCs), comprising:
isolating leukocytes from peripheral blood of an individual, by
apheresis and reducing platelet contamination and anticoagulants from
the apheresis product,
isolating mononuclear cells comprising monocytes and
lymphocytes from red cells and granulocytes of the apheresis product
in order to have less than 10% granulocytes and less than 5% red
cells, and
culturing said mononuclear cells in hydrophobic bags in a
culture medium containing IL-13 and GM-CSF, for a time sufficient
to obtain differentiated MD-APCs, and recovering the MD-APCs and
lymphocytes.

(App. Br. 12, Claims Appx.).

4 Claim 23 has been reformatted to add indentations. (See 37 C.F.R. §
1.75(i)).
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2. Appellants’ specification provides that “the expression
‘macrophages’ designates not only macrophages but antigen presenting cells
which derive from monocytes and which will be hereafter designated by
MD-APC.” (Spec. 4, ll. 28-30).
3. Chokri teaches that “[a]ntitumoral macrophages (MAK) were
obtained by the culture of human mononuclear cells in hydrophobic bags.”
(Chokri abstract).
4. Chokri teaches that “[l]eukocytes from normal thrombocyte
donors were isolated from peripheral blood by cytapheresis5. . . . After
collection of platelets for transfusion purposes, the concentrated leukocyte
apheresis residue was resuspended. Human mononuclear cells were
collected by 15 min centrifugation at 1000g . . . .” (Chokri 2257, right col.).
5. Chokri teaches that “[t]he addition of GM-CSF [to isolated
mononuclear cells] increased significantly (p<0.001) the macrophage
recovery (result of 12 different cultures).” (Chokri 2259, left col.).
6. Chokri does not teach culturing mononuclear cells in a culture
medium containing IL-13.
7. Chokri was authored by two of the named inventors, Mohamed
Chokri and Jacques Bartholeyns, of the instant application.
8. Jacobsen teaches that
IL-13, but not IL-4 synergistically enhanced colony formation
of Lin-Sca-1+ progenitors in response to granulocyte/macrophage
colony-stimulating factor (GM-CSF)(threefold) . . . . the
addition of IL-13 resulted in the production of macrophages
exclusively. This novel effect on differentiation was directly

5 We understand cytapheresis to be a type of apheresis.
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mediated, shared with IL-4, and could not be observed on Lin-
Sca-1- progenitor cells.

(Jacobsen abstract).
IV. ISSUE
Would those of skill in the art have had reason to include IL-13 with
GM-CSF in the culture medium of mononuclear cells to obtain differentiated
MD-APCs?
V. ANALYSIS
Appellants’ method requires isolating first leukocytes and then
mononuclear cells from blood, followed by “culturing said mononuclear
cells in hydrophobic bags in a culture medium containing IL-13 and GM-
CSF, for a time sufficient to obtain differentiated MD-APCs . . . .” (FF6 1).
Chokri teaches culturing isolated mononuclear cells in GM-CSF (FF
5), but not in IL-13 (FF 6). Jacobsen teaches that IL-13 acts synergistically
with GM-CSF to enhance colony formation of Lin-Sca1+ progenitors and
their differentiation into macrophages. (FF 8). The Examiner concluded that
Jacobsen teaches that IL-13 acts as an APC growth factor and that those of
skill in the art would have had reason to combine the teachings of Chokri
and Jacobsen to obtain MD-APCs by culturing in GM-CSF and IL-13.
Appellants argue that Chokri and Jacobsen are concerned with
producing macrophages, not MD-APCs. (App. Br. 8). However, Appellants’
specification indicates that “macrophages” include “MD-APCs.” (FF 2).
Chokri , which was authored by two of the named inventors (FF7), concerns

6 Finding of fact.
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macrophages which we understand, based on a disclosure from these same
inventors, to include MD-APCs. (FF 2). Similarly, it was reasonable for the
Examiner to find that “macrophages,” as used in Jacobsen, includes “MD-
APCs.” Appellants have not directed us to evidence showing why would
should not accept that “macrophages” includes “MD-APCs” as is disclosed
in its specification. Thus, we are not persuaded that the “macrophages”
discussed in Chokri and Jacobsen do not fall within the scope of Appellants’
claim.
Appellants argue that the teaching in Jacobsen to use IL-13 relates to a
particular cell type, Lin-Sca-1+ bone marrow cells, but that IL-13 had no
effect or even a negative effect on the proliferation of other cells,
specifically Lin-Sca-1- bone marrow cells. (See App. Br. 6-7). According to
Appellants, that IL-13 has a negative effect on some cells “teaches away”
from culturing in medium with both GM-CSF and IL-13. (App. Br. 7).
“A reference may be said to teach away when a person of ordinary
skill, upon reading the reference, would be discouraged from following the
path set out in the reference, or would be led in a direction divergent from
the path that was taken by the applicant.” In re Gurley, 27 F.3d 551, 553
(Fed. Cir. 1994). Jacobsen expressly teaches that IL-13 synergistically
enhanced colony formation in response to GM-CSF in some cells. (FF 8).
Appellants have not provided evidence to persuade us that those of skill in
the art would have looked to the results with Lin-Sca-1- cells over the results
with Lin-Sca-1+ cells. Thus, Appellants have not persuaded us that Jacobsen
would have discouraged those in the art from culturing mononuclear cells in
IL-13 and GM-CSF to derive MD-APCs.
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Appellants also argue that Figure 1 of Jacobsen shows that growth
factor combinations other than IL-13 and GM-CSF provided superior results
in enhancing antigen presenting cell generation and proliferation. (App.
Br. 7). “All the disclosures in a reference must be evaluated, including
nonpreferred embodiments . . . .” In re Mills, 470 F.2d 649, 651 (CCPA
1972). Thus, whether or not Jacobsen teaches using other growth factors, it
teaches culturing in a combination of IL-13 and GM-CSF, and so was
properly combined with the teachings of Chokri to render the claimed
method obvious.
Appellants argue that those of skill in the art would not expect the
results with mouse hematopoietic progenitor bone marrow cells in Jacobsen
to be applicable to the results with human mononuclear cells in Chokri. (See
App. Br. 8). “Obviousness does not require absolute predictability, but a
reasonable expectation of success is necessary.” In re Clinton, 527 F.2d
1226, 1228 (CCPA 1976). The Examiner found that because mononuclear
cells are derived from progenitor bone marrow cells, there is a reasonable
expectation that the results of Chokri and Jacobsen are relevant to each
other. (Ans. 7). Appellants have not directed us to evidence to the contrary.
Thus, we are not persuaded that would skilled in the art would have lacked
an expectation of success in combining the teachings of Chokri and
Jacobsen.
VI. CONCLUSION OF LAW
Those of skill in the art have had reason to include IL-13 with GM-
CSF in the culture medium of mononuclear cells to obtain differentiated
MD-APCs.
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VII. REJECTIONS UNDER 35 U.S.C. § 112, FIRST PARAGRAPH
The Examiner asserted that three claim elements lack sufficient
written description in the specification and so are new matter. The elements
are:
• “reducing platelet contamination” in claims 23 and 26;
• “culturing said mononuclear cells in hydrophobic bags” in
claims 23, 26, and 30; and
• culture medium comprising “crude antigens, peptides, cDNA,
genetic material or bispecific antibodies,” in claim 29.
According to the Examiner, the Specification does not teach these
limitations generically, but only discloses specific examples. (Ans. 8-9).
The specification provides:
• “The apheresis product is centrifuged for 10 min at 280 g in
order to reduce platelet contamination.” (Spec. 12, ll. 1-3).
• “The monocyte derived antigen presenting cells (MD-APCs)
are obtained after 5-15 days in culture of mononuclear cells in
hydrophobic bags in EVA (Ethylene Vinyl Acetate/STEDIM)
or equivalent bags (Teflon) . . . .” (Spec. 15, ll. 22-24).
• “The invention also relates to a process wherein the culture
medium of MD-APCs is added
-with crude antigens, for instance . . .
-specific peptides against which an immune response is
desired,
-cDNA or genetic material linked to vectors (for example
. . . ) to allow transfection . . .
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-or bispecific antibodies . . . . (Spec. 7, ll. 21-30).
Whether the inventor has provided adequate written description must
be determined from the disclosure considered as a whole. Reiffin v.
Microsoft Corp., 214 F.3d 1342, 1345-46 (Fed. Cir. 2000). The Examiner
has not explained why one skilled in the art would not have considered
Appellants to have been in possession of an invention of the scope claimed
given the entirety of the disclosure. The Examiner, for instance, does not
argue or point to evidence suggesting that there is sufficient unpredictability
in the art such that one skilled in the art would not have accepted that
Appellants were in possession of the method as claimed. See Bilstad v.
Wakalopulos, 386 F.3d 1116, 1125 (Fed. Cir 2004). Thus, we do not find a
lack of written description for the terms recited in the claims. Accordingly,
the Examiner erred in rejecting the claims under 35 U.S.C. § 112, first
paragraph.
VIII. ORDER
Upon consideration of the record and for the reasons given,
the rejection of claims 23-31 under 35 U.S.C. § 103(a) over Chokri
and Jacobsen is AFFIRMED; and
the rejection of claims 23-31 under 35 U.S.C. § 112, first paragraph, is
REVERSED.

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv) (2007).

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AFFIRMED

saw

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