Ex Parte Min et al

Patent Trials and Appeals Board

Feb 13, 2019

13760774 - (D) (P.T.A.B. Feb. 13, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/760,774 02/06/2013
26371 7590 02/15/2019
FOLEY & LARDNER LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
UNITED ST A TES OF AMERICA
FIRST NAMED INVENTOR
Kyungyoon Min
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
F-6599 (091474-0125) 6498
EXAMINER
MOSS, NATALIE M
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
02/15/2019 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):
ipdocketing@foley.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KYUNGYOON MIN,
KATHERINE RADWANSKI, and CHERYL HEBER
(APPLICANT: FENWAL, INC.)
Appeal2017-007988 1
Application 13/760,7742
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
RYAN H. FLAX, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This Appeal under 35 U.S.C. § 134(a) involves claims 1--4, 6-10, 13,
21-27, and 30--41 (Final Act. 3 1). Examiner entered rejections under 35
U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 The record includes a transcript of the oral hearing held February 7, 2019.
2 Appellants identify "Fenwal, Inc." as the real party in interest (App. Br. 1 ).
3 Examiner's May 23, 2016 Final Office Action.
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Application 13/760,774
STATEMENT OF THE CASE
Appellants' disclosure relates to extracorporeal photopheresis (ECP)
treated "mononuclear cells that retain their apoptotic properties after
cryopreservation and subsequent thawing" (Spec. ,r 1 ). According to
Appellants, "[ t ]here are several diseases or disorders which are believed to
primarily involve mononuclear cells, such as cutaneous T-cell lymphoma,
organ allograft rejection after transplantation, graft versus host disease and
autoimmune diseases such as rheumatoid arthritis, systemic sclerosis, among
others" (Spec. ,r 3). In this regard, Appellants disclose:
Where existing therapies for treating one or more
diseases may result in certain unintended side effects, additional
treatment may be desired or required. One known procedure
which has been shown to be effective in the treatment of
diseases and/ or the side effects of existing therapies is
extracorporeal photopheresis or "ECP". Extracorporeal
photopheresis ( also sometimes referred to as extracorporeal
photochemotherapy) is a process that includes: (1) collection of
mononuclear cells "MNC" from a patient, (2) photoactivation
treatment of the collected mononuclear cells, and (3) reinfusion
of the treated mononuclear cells back to the patient. More
specifically, ECP involves the extracorporeal exposure of
peripheral blood mononuclear cells combined with a
photoactive compound, such as 8-methoxypsoralen or
"8-MOP" which is then photoactivated by ultraviolet light,
followed by the reinfusion of the treated mononuclear cells. It
is believed that the combination of 8-MOP and UV radiation
encourages and/or causes apoptosis or programmed cell death
( also referred to herein as the "apoptosis trend") of ECP treated
cells.
(Spec. ,r 8.) Thus, as Appellants disclose, the extracorporeal exposure of a
composition comprising peripheral blood mononuclear cells and 8-MOP to
ultraviolet light was known in the art at the time of Appellants' claimed
invention as ECP (id.). In addition, it was appreciated, at the time of
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Appellants' claimed invention, that ECP treatment induces an apoptosis
trend in mononuclear cell product (id.). Further, as discussed below, the
prior art disclosed methods of cryopreserving mononuclear cells before and
after ECP treatment.
Against the foregoing background, we find Appellants' claims 1, 10,
13, 22, and 30 representative and reproduce these claims below:
1. A method of providing a cryopreserved extracorporeal
photopheresis treated mononuclear cell product from whole
blood of a patient into whom the treated product will be re-
infused, comprising:
treating a mononuclear cell product with a treatment that
induces an apoptosis trend in the mononuclear cell product,
wherein the treatment comprises
combining the mononuclear cell product with
8-methoxypsoralen, and exposing the mononuclear cell
product combined with said 8-methoxypsoralen to
ultraviolet light at a dose of from about 0.5 J/cm2 to
about 5.0 J/cm2 to obtain a treated mononuclear cell
product having an apoptosis trend,
combining at least a portion of the treated mononuclear
cell product having an apoptosis trend with a cryopreservation
medium, and
cryopreserving at least said portion of said treated
mononuclear cell product to obtain a population of
cryopreserved mononuclear cells in which the apoptosis trend is
not significantly affected upon thawing.
(Claims App. 4 1.)
10. A cryopreserved extracorporeal photopheresis treated
mononuclear cell product comprising:
about 50 mL to about 300 mL of a mononuclear cell
product that has been treated to have an apoptosis trend by a
4 Appellants' November 4, 2016 "CLAIMS APPENDIX".
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treatment that comprises combining the mononuclear cell
product with 8-methoxypsoralen and exposing the mononuclear
cell product combined with said 8-methoxypsoralen to a dose of
ultraviolet light of from about 0.5 J/cm2 to about 5.0 J/cm2
sufficient to produce an apoptosis trend in the product; and
about 50 mL to about 300 mL of a cryopreservation solution,
the apoptosis trend of the cryopreserved mononuclear cells
being not significantly affected upon thawing.
(Id. at 2)
(Id.)
13. The product of claim 10 wherein the mononuclear cell
product is combined with about 100-300 nanograms/mL of
8-methoxypsoralen prior to exposure to ultraviolet light.
22. The method of claim 1 wherein the cryopreserved
mononuclear product has a percentage of apoptotic
lymphocytes of greater than 80% after culturing for 72 hours
after thawing.
(Id. at 3.)
(Id.)
30. The method of claim 1, wherein the mononuclear cell
product is exposed to light at a dose of from about 1 to 2 J/cm2.
Grounds of rejection before this Panel for review:
Claims 1-3, 6-10, 13, 21-27, 30-37, 40, and 41 stand rejected under
35 U.S.C. § 103(a) as unpatentable over Greenman. 5
Claims 1, 21, 38, and 39 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Greenman and Merlin. 6
5 Greenman et al., WO 99/03976, published Jan. 28, 1999.
6 Etienne Merlin, et al., Use of cryopreserved autologous cells for
extracorporeal photochemotherapy: clinical applications, 51
TRANSFUSION 1296-99 (2011).
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Claims 1--4, 6-10, 21, 22, and 30-39 stand rejected under 35 U.S.C.
§ I03(a) as unpatentable over the combination of Peritt7 and Merlin.
Claims 13, 40, and 41 stand rejected under 35 U.S.C. § I03(a) as
unpatentable over the combination of Peritt, Merlin, and Tokura. 8
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Greenman "relates to cell compositions that are incapable of
proliferation but retain function, and the methods of preparation and use of
such compositions. More specifically, the present invention relates to
methods for preparing proliferation inhibited leukocytes for use in
transfusion" (Greenman 1:9--12; see also id. at 6:32 -7:2 (Greenman
"provides an effective method for treating leukocytes from an allogeneic
donor to produce leukocytes that are unable to proliferate but maintain
viability and immune function effective to promote destruction of a diseased
cell or pathogen"); see Ans. 9 2).
FF 2. Greenman' s
leukocyte population of the invention is, on the whole,
incapable of proliferation but retains immunological activity.
This leukocyte population will be capable of the following
activities, among others:
1. Promoting destruction of a diseased cell, an infected
cell, or a pathogen.
7 Peritt et al., US 2003/0139466 Al, July 24, 2003.
8 Yoshiki Tokura et al., Treatment ofT Lymphocytes with 8-Metoxypsoralen
Plus Ultraviolet A Induces Transient but Biologically Active Thi -Skewing
Cytokine Production, 113 J. INVEST DERMATOL 202---08 (1999).
9 Examiner's March 8, 201 7 Answer.
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2. Facilitating the engraftment of a second population of
cells. The second population of cells can be a suspension of
cells or an organized collection of cells, such as a patch of
tissue or an organ. Such cells can include, for instance,
hematopoietic cells, myeloid cells, leukocytes, bone marrow
cells, islet cells, hepatic cells, neuronal cells, myocardial cells,
mesenchymal cells and endothelial cells.
3. Promoting immune reconstitution.
4. Immunotherapy.
5. Treatment of mixed chimerism.
6. Promoting a graft-vs.-leukemia (GVL) response.
(Greenman 7:22-8: 1.)
FF 3. Greenman discloses a method for preparing a treated, i.e.,
proliferation inhibited, leukocyte population, wherein a leukocyte population
is treated with a compound, i.e., 8-methoxy psoralen (8-MOP), one of
Greenman's preferred psoralens that is capable of forming a covalent bond
with a nucleic acid comprising a photoactivatable moiety, wherein upon
electromagnetic stimulation, i.e., ultraviolet light at a dosage of between 10-3
to 100 J/cm2, the compound forms a covalent bond with leukocyte genomic
DNA (Greenman 9:27-10: 16; see id. at 42:30-31 ("stock psoralen solutions
are added to suspensions of purified donor leukocyte populations to the
desired final concentration"); id. at 43:3-5 (Greenman discloses that "PAP,"
a representative psoralen compound within the scope of Greenman's
disclosure, "is added to the purified leukocyte preparation at a concentration
of between 10-4 and 150 µM, preferably between 10-3 and 150 µM. The
leukocytes will generally be at a cell density of between about 10 to 109
cells/ml"); id. at 27:9-17 ("[l]eukocytes from the donor can be apheresed");
see also Ans. 2-3, 5, 7, and 8; and compare Spec. ,r,r 12, 13 (Appellants
disclose that "[ c ]urrently, known [ extracorporeal photopheresis (ECP)]
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treatment procedures" involve "the apheresis collection of a mononuclear
cell product from a patient, the addition of 8-MOP to the collected cell
product, subsequent UV irradiation and the reinfusion of the treated
mononuclear cell product" into the patient and "that ECP treatment directly
promotes and encourages apoptosis of lymphocytes following exposure to
UV light"); see also Radwanski Dec. 10 ,r 4).
FF 4. Greenman' s
treated leukocyte populations can subsequently be used to
infuse a patient. The following alternative scenarios are also
possible: i) collection of peripheral blood, processing,
leukocyte treatment, and infusion; ii) collection, processing,
leukocyte treatment, freezing of treated cells, washing off of
cryopreservative, and infusion; iii) vaccination of donor ( one or
more times) with a target antigen to expand antigen-specific T
cells, collection of peripheral blood from vaccinated donor,
processing, treatment, and infusion; iv) in vitro sensitization of
donor leukocytes with a target antigen to expand antigen-
specific T cells, leukocyte treatment, and infusion.
(Greenman 29: 1-8; see Ans. 4--5.)
FF 5. Greenman discloses that "treated leukocytes can be cryopreserved
using methods known in the art such as by control rate freezing in 10%
DMSO and storage in liquid nitrogen" and "[ w ]hen needed for transfusion,
the frozen leukocytes will be thawed and washed to remove the DMSO"
(Greenman 27:18-22; see Ans. 3, 5, 7, and 8).
10 December 4, 2014 Declaration of Katherine Radwanski, M.S.
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FF 6. Greemnan's Figure 1 is reproduced below:
Reduction of Proliferating T-cells after
PCT With Various Concentrations of
' 0.01 0.1 t
Dose µM
PAP-1 (o)
A.MT (6)
8-MOP (O)
(UVA=1J/cm2)
~
10 ,oo
Fig~ 1
Greenman's Fig. 1 illustrates "[t]he dose related effect of photochemical
treatment [(PCT)] with S-59 (Squares), 4'-aminomethyl 4,5',8-
trimethylpsoralen [AMT] (triangles), and 8-methoxypsoralen [8-MOP]
(circles) on leukocytes in platelet concentrates (PC)" (Greenman 52:3-5
(alteration original); see Ans. 3--4).
FF 7. Examiner finds that Greenman makes obvious Appellants' claimed
invention with the exception of "specifically teach[ing] that cells are to be
rapidly thawed at 3 7 degrees Celsius with a water bath" and relies on Merlin
to make up for this deficiency in Greenman (Ans. 8-9).
FF 8. Peritt
relates to the administration of extracorporeal photopheresis
("ECP") and/ or apoptotic cells to prevent, or reduce the
potential severity of, GVHD and/or transplant or implant
rejection in patients about to undergo a transplant or implant
procedure. The present invention further relates to the
administration of ECP and/or apoptotic cells to prevent, delay,
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or reduce the potential severity of, autoimmune diseases and
atopic diseases in subjects predisposed to such diseases.
(Peritt ,r 3 8; see also id. Abstract; id. ,r 2; id. ,r 41 ("'ECP' refers to
extracorporeal photopheresis, also known as extracorporeal phototherapy.
[Peritt] ... relates to the use of ECP to prevent or reduce the potential
severity of graft-versus-host-disease in a transplant recipient about to
undergo a transplant"); id. ,r 68; see Ans. 9--10).
FF 9. Peritt discloses the administration of a
photosensitive compound ... [to a] subject's blood, recipient's
blood, or the donor's blood following its withdrawal from the
subject, recipient, or donor, respectively, and prior to or
contemporaneously with exposure to ultraviolet light. The
photosensitive compound may be administered to whole blood
or a fraction thereof provided that the target blood cells or
blood components receive the photosensitive compound. A
portion of the subject's blood, recipient's blood, or the donor's
blood could first be processed using known methods to
substantially remove the erythrocytes and the photoactive
compound may then be administered to the resulting enriched
leukocyte fraction. In one embodiment, the blood cells
comprise white blood cells, specifically, T-cells.
(Peritt ,r 46; see id. ,r 53 ("when the photopheresis step is carried out in vitro,
at least a fraction of the treated blood is returned to the subject, recipient, or
donor. The treated blood or the treated enriched leukocyte fraction ... may
then be administered back to the subject, recipient, or donor"); id. ,r 114
("The effective amount of apoptotic cells of [Peritt's] invention may include
a pharmaceutically acceptable excipient[, such as,] sterile water, sterile
saline, phosphate buffered saline, and the like"); see Ans. 9--10 and 13.)
FF 10. Peritt's "photoactivatable or photosensitive compounds ... include,
but are not limited to, psoralen and psoralen derivatives; [ such as]
8-methoxypsoralen" (Peritt ,r 48; see Ans. 9).
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FF 11. Peritt discloses that "blood to which the photoactive compound has
been administered is treated by subjecting the portion of the blood to
photopheresis using ultraviolet light ... [for] a duration of sufficient length
to deliver, for example, about 1-2 J/cm2 to the blood" (Peritt ,r 50; see Ans.
9--10).
FF 12. Examiner finds that Peritt does not specifically teach cryopreserving
cells obtained using its methodology and relies on Merlin to make up for this
deficiency in Peritt (see Ans. 10).
FF 13. Examiner finds that the combination of Peritt and Merlin fails to
suggest the use of 8-MOP at "a concentration of 100-300 nanograms/ml"
and relies on Tokura to make up for this deficiency in the combination of
Peritt and Merlin (Ans. 14; see also App. Br. 18 ("Tokura is cited for
teaching an ECP treatment method using 100 ng/ml 8-MOP")).
ANALYSIS
The rejection over Greenman:
Based on Greenman, Examiner concludes that, at the time Appellants'
invention was made, it would have been prima facie obvious to prepare,
through routine optimization, a composition comprising a leukocyte
population and 8-MOP in the ranges required by Appellants' claimed
invention and electromagnetically stimulate this composition with ultraviolet
light at a dosage of about 0.5 J/cm2 to about 5.0 J/cm2 and, through routine
optimization of methods known in the art, cryopreserve about 50 mL to
about 300 mL of this electromagnetically stimulated composition in about
50 mL to about 300 mL of cryopreservation solution (Ans. 3--4 and 5---6; see
FF 1---6).
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Claim 1:
Appellants' claim 1 is reproduced above.
Greenman discloses an ECP method wherein an apheresed collection
of mononuclear cells is isolated from a patient combined with 8-MOP,
exposed to UV irradiation, and then reinfusing the treated mononuclear cell
product, either before or after cryopreservation, back into a patient (see FF
3-5). As Appellants appreciate ( and their Specification describes), the ECP
method "directly promotes and encourages apoptosis of lymphocytes
following exposure to UV light" (FF 3). Therefore, we are not persuaded by
Appellants' contention that the evidence of record fails to support
Examiner's reasoning that Greenman's method necessarily results in a
population of leukocytes exhibiting "an apoptosis trend" (App. Br. 10; see
also Reply Br. 9-10). We find no limit on the phrase "apoptosis trend" in
Appellants' claim 1. Thus, given that no specific degree or amount of
apoptosis, or other physiological phenomenon, is required by Appellants'
claim 1 for an "apoptosis trend," any trend toward apoptosis resulting from
the psoralen and UV treatment of Greenman falls within the scope of claim
1.
For the foregoing reasons, we are not persuaded by Appellants'
contention that "Greenman subjects its cells to a different treatment to obtain
cells with different properties that are used for different purposes" and, thus,
"Greenman's treated leukocytes do not have an apoptosis trend, as recited in
... [Appellants'] claims, and that cells having such an apoptosis trend would
not be suitable for use in accordance with Greenman" (Id. at 10-11 ( citing
Radwanski Dec. ,r,r 6, 8, 9); cf Ans. 16 (Greenman's Figure 1 "illustrates an
'apoptotic trend' of treated cells"); id. ("Greenman teaches the same method
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steps of treating cells and is indistinguishable from ... [Appellants'
claims]")).
In addition, we recognize Appellants' contention that "apoptotic cells
cannot be considered to have the membrane integrity required of
Greenman's treated leukocytes that are capable of providing a GVL
response" (App. Br. 10-11 (citing Radwanski Dec. ,r 9) (emphasis added)).
This contention is not persuasive. Appellants' claimed invention and the
prior art at issue utilize a treatment method that induces an "apoptotic trend"
(see e.g., FF 3---6; cf Claims App. 1 ). Appellants provide no persuasive
reasoning or evidence to support a contention that an "apoptotic trend" is
equivalent to "apoptosis" (see App. Br. 10-11 ( citing Radwanski Dec. ,r 9);
cf Spec. ,r 8). To the contrary, an "apoptotic trend" simply relates to a
method of placing cells on a path toward apoptosis (see generally Spec. ,r 8).
Clearly, those of ordinary skill in this art would be able to distinguish
between those treated cells that are near death, i.e. apoptotic cells, and those
that, although trending toward apoptosis, are not near death and, thus, would
not have the types of membrane integrity concerns upon which Appellants
and Declarant appear to premise their argument and opinion.
For the foregoing reasons, we are not persuaded by Radwanski's
statement that "Greenman' s treated cells do not exhibit an apoptosis trend,
since they positively express at least two negative regulators of the apoptotic
process" (Radwanski Dec. ,r 1 O; see also App. Br. 11 ). In addition, we note
that although Radwanski makes reference to two documents to support its
statement, neither of these documents are of record in this administrative file
(see Radwanski Dec. ,r 10; id. at pg. 4, n. 1-2). Radwanski also makes
reference to "Kraemer et al., J. Inv. Derm. 77: 235-39 (1981)," which is
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also not of record in this application (see Radwanski Dec. ,r 11; see also
App. Br. 12-13; Reply Br. 8 ("The record includes detailed explanations and
supporting evidence in the form of the Radwanski Declaration (which itself
is supported by ... other scientific literature")). Thus, Radwanski' s
statements, and Appellants' corresponding reliance on Radwanski' s
statements, lack an evidentiary basis on this record.
As discussed above, Greenman discloses a method within the scope of
Appellants' claimed method that would have been reasonably expected to
result in the production of a product that would be identical to the cells and
process produced by Appellants' claimed method. In this regard, we note
that Greenman discloses exposing a composition comprising: (i) a leukocyte
population and (ii) varying concentrations of the psoralen S-59, with UVA
light at a dosage of 3.0 J/cm2, which falls within the scope of Appellants'
claimed invention and/or requires, based on Greenman's disclosure, nothing
more than routine experimentation (see Greenman 52:27-33 (addressing
Greenman's Figure 3); id. at 79:13-32 (addressing Greenman's Figure 10);
id. at 80:1-33 (addressing Greenman's Figure 12); see also id. at 10:18 (S-
59 is a psoralen); cf Radwanski Dec. ,r 10 (addressing Greenman's Figures
3, 10, and 12)). Taken as a whole, on this record, Appellants failed to
provide persuasive evidence or argument that establishes that their claimed
method: (a) differs from Greenman's and/or (b) results in the production of
a product that differs from a product produced by Greenman' s method.
Greenman discloses the use of ultraviolet light at a dosage of between
10-3 to 100 J/cm2 (FF 3). The method of Appellant's claim 1 recites a dosage
of ultraviolet light that is from about 0.5 to about 5.0 J/cm2, which falls
directly within the range disclosed by Greenman (Claims App. 1 ). "[W]here
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there is a range disclosed in the prior art, and the claimed invention falls
within that range, there is a presumption of obviousness." Iron Grip Barbell
Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004). Therefore,
we are not persuaded by Appellants' contentions regarding whether
Greenman makes obvious the dosage range of ultraviolet light required by
Appellants' claimed invention (see App. Br. 11-12; Reply Br. 10; cf Ans.
16 (Appellants have "not provided any evidence of non-obviousness or non-
obviousness of the range")).
Although Greenman uses psoralen S-59 11 in a preferred embodiment
of its disclosure, Greenman identifies that preferred psoralens that fall within
the scope of its invention, include 8-MOP (FF 3; cf App. Br. 12 (citing
Radwanski Dec. ,r 11); Reply Br. 9-10). A prior art disclosure is available
for all that it discloses and suggests to one of ordinary skill in the art. See In
re Lamberti, 545 F.2d 747, 750 (CCPA 1976).
For the foregoing reasons, we are not persuaded by Appellant's
contention that "Greenman itself teaches away from using 8-MOP and UV-
A light at doses that inactivate T cell function" (App. Br. 12-13 (citing
Radwanski Dec. ,r 11); see Reply Br. 10). For the same reasons, we are not
persuaded by Appellants' contention that "Examiner Improperly Elevates
Her Opinion Over The Evidence Of Record" or that this "record shows that
when Greenman is applied as it would have been understood by a person of
ordinary skill in the art, it does not suggest the claimed methods or products"
(App. Br. 14). To the contrary, for the reasons set forth above, the
preponderance of evidence on this record fails to support Radwanski' s
11 See Greenman 10: 17-18 ("[i]n a preferred embodiment, the method ...
employs the psoralen referred to herein as S-59").
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statements or Appellants' contentions. For the same reasons we are not
persuaded by Appellants' contentions regarding the optimization of
Greenman's disclosure (Reply Br. 8-9).
Claim 13:
Appellants' claim 13 is reproduced above. As Appellants explain,
their claim 13 "recite[s] that the mononuclear cell product is 'combined with
about 100-300 nanograms/mL of 8-methoxypsoralen prior to exposure to
ultraviolet light"' (App. Br. 15; Reply Br. 11).
As discussed above, Greenman discloses a method wherein "stock
psoralen[, i.e., 8-MOP,] solutions are added to suspensions of purified donor
leukocyte populations to [a] desired final concentration" and the resulting
composition is treated with ultraviolet light at a dosage of between 10-3 to
100 J/cm2 to produce a cryopreserved extracorporeal photopheresis treated
mononuclear cell product (FF 3). In this regard, Greenman discloses the
addition of PAP, a representative psoralen compound within the scope of
Greenman' s disclosure "to [a] purified leukocyte preparation at a
concentration of between 10-4 and 150 µM" (id.). Thus Greenman provides
a concentration range for administering psoralen compounds from stock
solutions to cells and discloses that a person of ordinary may add a psoralen
compound, such as 8-MOP, to a cell suspension to achieve a desired final
psoralen, i.e. 8-MOP, concentration (id.). "[W]here the general conditions
of a claim are disclosed in the prior art, it is not inventive to discover the
optimum or workable ranges by routine experimentation." In re Aller, 220
F.2d 454,456 (CCPA 1955).
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For the foregoing reasons, we are not persuaded by Appellants'
contention that a person of ordinary skill in this art would not have
optimized the psoralen concentration of between 10-4 and 150 µM in
Greenman's method to obtain a desired, or optimum, final concentration (see
App. Br. 15; Reply Br. 11 ).
Claim 22:
Appellants' claim 22 is reproduced above. As Appellants' explain,
their claim 22 "recite[ s] that 'the cryopreserved mononuclear product has a
percentage of apoptotic lymphocytes of greater than 80% after culturing for
72 hours after thawing"' (App. Br. 16).
For the reasons discussed above, Greenman makes obvious a method,
of producing a cryopreserved extracorporeal photopheresis treated
mononuclear cell product within the scope of Appellants' claimed invention
(see FF 1-7). Therefore, we are not persuaded by Appellants' contention
that "there is no factual basis whatsoever for the Examiner's assertion that
the features recited in [Appellants'] claim[] [22] ... would be inherent to
Greenman's cells" (App. Br. 16-17; see Reply Br. 11-12).
Claim 30:
Appellants' claim 30 is reproduced above. As Appellants' explain,
their claim 30 "recite[s] that the mononuclear cell product is 'exposed to
light at a dose of from about 1 to 2 J/cm2" (App. Br. 16).
As discussed above, Greenman discloses a method wherein a
composition, comprising a donor leukocyte population and 8-MOP, is
exposed to ultraviolet light at a dosage of between 10-3 to 100 J/cm2 (FF 3;
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see Ans. 17). "[W]here there is a range disclosed in the prior art, and the
claimed invention falls within that range, there is a presumption of
obviousness." Iron Grip Barbell Co., 392 F.3d at 1322.
Therefore, we are not persuaded by Appellants' contention that
Greenman fails to make obvious Appellants' claimed method (see App. Br.
16; Reply Br. 11).
The rejection over the combination of Greenman and Merlin:
Appellants' claim 1 is representative and reproduced above.
Based on the combination of Greenman and Merlin, Examiner
concludes that, at the time Appellants' invention was made, it would have
been prima facie obvious to use the protocol disclosed by Merlin to thaw
cryopreserved cells produced according to Greenman's method (see Ans. 9;
see also FF 1-7; Ans. 17-18).
Appellants contend:
Merlin does not teach or suggest cryopreserving cells after ECP
treatment or cryopreserving treated mononuclear cells having
an apoptosis trend, let alone teach or suggest a method of
cryopreserving treated mononuclear cells having an apoptosis
trend in a manner that yields a population of cryopreserved
mononuclear cells in which the apoptosis trend is not
significantly affected upon thawing,
which is disclosed by Greenman (see App. Br. 15; cf FF 3-5). Therefore,
having found no deficiency in the combination of Greenman and Merlin, we
are not persuaded by Appellants' contention that "Merlin does not cure
[Appellants' alleged] deficiencies" in Greenman (App. Br. 15).
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Application 13/760,774
The rejection over the combination of Peritt and Merlin:
Based on the combination of Peritt and Merlin, Examiner concludes
that, at the time Appellants' invention was made, it would have been prima
facie obvious to utilize Merlin's cryopreservation methodology "to
cryopreserve the cells produced by Peritt. Peritt teaches a method of
obtaining cells for extracorporeal photochemotherapy, and Merlin teaches
that cryopreserving cells used for photochemotherapy is advantageous"
(Ans. 10). Therefore, Examiner reasons, "[ o ]ne would be motivated to
[ combine Peritt with Merlin,] because Peritt teaches that patients receiving []
treatment need multiple infusions, and Merlin teaches that cryopreserving
cells dramatically reduces the number of apheresis sessions" (id.).
Claim 1:
Appellants' claim 1 is reproduced above.
Appellants' contend that because "Peritt does not discuss
cryopreserving its ECP-treated cells" and Merlin discloses the
cryopreservation of cells "prior to ECP treatment," Examiner's conclusion
of obviousness is based on improper hindsight (App. Br. 17). We are not
persuaded. Notwithstanding Appellants' contention to the contrary,
Examiner provides a reason why a person of ordinary skill in this art would
have cryopreserved cells, specifically, because cryopreserving cells
dramatically reduces the number of apheresis sessions necessary for the
multiple infusions required by Peritt's disclosed treatment (see Ans. 10; see
also id. 19). Absence evidence to the contrary, of which Appellants offer
none, we find the choice of cryopreserving cells either before or after ECP
treatment to represent nothing more than routine optimization of the
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methodology suggested by the combination of Peritt and Merlin. See Aller,
220 F.2d at 456. We find no evidence on this record to support a conclusion
that the choice of timing of cryopreservation either before or after treatment
is unobvious "in the absence of any proof in the record that the order of
performing the steps produces any new and unexpected results." In re
Burhans, 154 F.2d 690, 692 (CCPA 1946). We also find no evidence on this
record to support a conclusion that by optimizing the cryopreservation
methodology suggested by the combination of Peritt and Merlin to
cryopreserve cells after ECP treatment will not necessarily result in a
population of cryopreserved mononuclear cells in which the apoptosis trend
is not significantly affected upon thawing ( as required by Appellants' claim
1 ), including wherein the cryopreserved mononuclear product has a
percentage of apoptotic lymphocytes of greater than 80% after culturing for
72 hours after thawing, as required by Appellants' claim 22 (cf App. Br. 17-
18). In this regard, we find no evidence on this record to support a
conclusion that there would have been "no reasonable expectation of success
in being able to maintain the apoptosis trend after cryopreservation and
thawing, such that the apoptosis tread is not significantly affected upon
thawing, as recited in [Appellants'] ... claims" (Reply Br. 13).
Claim 22:
Appellants' claim 22 is reproduced above.
For the reasons set forth above, we are not persuaded by Appellants'
contention that "there is no factual basis whatsoever for the Examiner's
assertion that the features recited in claim 22 would be inherent to the
combination of Peritt and Merlin" (App. Br. 18).
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The rejection over the combination of Peritt, Merlin, and Tokura:
Appellants' claim 13 is representative and reproduced above.
Based on the combination of Peritt, Merlin, and Tokura, Examiner
concludes that, at the time Appellants' invention was made, it would have
been prima facie obvious to use 100 nanograms/ml of 8-MOP, as suggested
by Tokura, to obtain the cryopreserved extracorporeal photopheresis treated
mononuclear cell product suggested by the combination of Peritt and Merlin
(Ans. 14).
Having found no deficiency in the combination of Peritt and Merlin,
we are not persuaded by Appellants' contention that T okura fails to make up
for Appellants' alleged deficiencies in the combination of Peritt and Merlin
(App. Br. 18; see also Reply Br. 13-14).
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
The rejection of claims 1, 13, 22, and 30 under 35 U.S.C. § 103(a) as
unpatentable over Greenman is affirmed. Claims 2, 3, 6-10, 21, 25-27, 32-
3 7 are not separately argued and fall with claim 1. Claims 40 and 41 are not
separately argued and fall with claim 13. Claims 23 and 24 are not
separately argued and fall with claim 22. Claim 31 is not separately argued
and falls with claim 30.
The rejection of claim 1 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Greenman and Merlin is affirmed. Claims 21, 38,
and 39 are not separately argued and fall with claim 1.
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Application 13/760,774
The rejection of claims 1 and 22 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Peritt and Merlin is affirmed. Claims
2--4, 6-10, 21, and 30-39 are not separately argued and fall with claim 1.
The rejection of claim 13 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Peritt, Merlin, and Tokura is affirmed. Claims 40
and 41 are not separately argued and fall with claim 13.
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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