Ex Parte Segal

Patent Trial and Appeal Board

Sep 26, 2016

12851243 (P.T.A.B. Sep. 26, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/851,243 08/05/2010
2101 7590 09/28/2016
Sunstein Kann Murphy & Timbers LLP
125 SUMMER STREET
BOSTON, MA 02110-1618
FIRST NAMED INVENTOR
Andrew H. Segal
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.
3915/1004 1361
EXAMINER
BEL YA VSKYI, MICHAIL A
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
09/28/2016 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):
usptomail@sunsteinlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANDREW H. SEGAL 1
Appeal2015-002529
Application 12/851,243
Technology Center 1600
Before JOHN G. NEW, RICHARD J. SMITH, and TIMOTHY G.
MAJORS, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of stimulating an immune response to an antigen. We have jurisdiction
under 35 U.S.C. § 6(b).
We affirm.
1 According to Appellant, the real party in interest is OpsaniTx LLC. (Br.
3.)
Appeal2015-002529
Application 12/851,243
STATEMENT OF THE CASE
Background
"Cytokines are polypeptide molecules that regulate immune and/or
inflammatory reactions by binding to cell-surface receptors on leukocytes ...
Some cytokines can be grouped into families based on similarities of
structure and/or function. Examples of such families include ... colony-
stimulating factors (CSP's)." (Spec. 1, 11. 11-12 and 17-19.)
"CSP's []are grouped together because of their abilities to promote
differentiation of bone marrow cells into selected types of leukocytes ....
Examples of CSP's include ... Granulocyte-Macrophage CSP (GM-CSP)."
(Id. 2, 11. 12-15.)
Claims on Appeal
Claims 1, 3, 4, 10-18, and 20-23 are on appeal. (Claims Appendix,
Br. 17-20.) Independent claim 1 is illustrative and reads as follows:
1. A method of stimulating an immune response to an antigen,
the method comprising
administering to a mammal a composition comprising a
cell that provides said antigen and has an engineered cytokine
bound to the cell surface, said engineered cytokine including:
( 1) a first portion from a cytokine which is a ligand for the GM-
CSP receptor, and (2) a second portion heterologous to said
cytokine, said second portion being capable of binding to said
cell when said engineered cytokine is mixed with said cell
exogenously, wherein said cell is produced by incubating cells
with isolated engineered cytokine in a preparation consisting of
cells and engineered cytokine, wherein said cytokine is isolated
prior to formation of the preparation, and
wherein an immune response is stimulated in said
mammal to said antigen following administration of said
composition.
(Br. 17.)
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Application 12/851,243
Examiner's Rejection
Claims 1, 3, 4, 10-18, and 20-23 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over Hiserodt2 in view of the Known fact disclosed
in the Specification at pages 52-54 and 66-68 ("Known fact"). (Final Act.
2.)3
FINDINGS OF FACT
We adopt as our own the Examiner's findings and analysis concerning
the scope and content of the prior art. The following findings are included
for emphasis and reference convenience.
FF 1. The Specification states that the term opsonin "refers to naturally
occurring and non-naturally occurring molecules which bind to both
antigens and antigen presenting cells ... it is believed that opsonin-enhanced
cells ... allow more efficient binding, engulfment, and internalization of the
antigen." (Spec. 52, 11. 5---6 and 13-16.)
FF 2. The Specification states that "[m]oieties through which molecules can
be stably bound to a cell include crosslinking moieties, transmembrane
sequences, and lipid moieties. The preparation of proteins containing these
sequences or moieties is well-known to one of skill in the art." (Id. 54, 11.
25-28.)
FF 3. The Specification states that "[t]he attachment of a lipid ... to a
molecule ... can permit the complex to become stably associated with the
plasma membrane when the complex is admixed with a cell." (Id. 66, 11. 2-
4.)
2 Hiserodt et al., US 6,277,368 Bl, issued Aug. 21, 2001 ("Hiserodt").
3 Office Action mailed Nov. 13, 2013.
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Application 12/851,243
FF 4. The Examiner finds that the Specification discloses "several prior art
references teaching that the attachment of a lipid, e.g. long-chain fatty acid
to a polypeptide[,] permit[ s] the complex to become stably associated with
the plasma membrane when the complex is admixed with the cell
(emphasis added)." (Final Act. 5, citing Spec. 66.)
FF 5. The Examiner finds that "at the time the invention was made one [of]
skill in the art would know how to produce[] an engineered membrane-
bound form of cytokine, comprising [a heterologous] moiety wherein said
moiety binds to the cell." (Final Act. 4, citing Known fact.)
FF 6. Hiserodt teaches methods of using vaccines in cancer immunotherapy,
wherein the vaccines comprise a tumor associated antigen and cytokines in
the secreted or membrane bound form. (Hiserodt Abstract.)
FF 7. The Examiner finds that Hiserodt "teaches that [the] cytokine is a
GM-CSP, that is a ligand for GM-CSP receptor." (Final Act. 4, citing
Hiserodt col. 7, 1. 31 and col. 10, 11. 52---65.)
FF 8. Hiserodt teaches that "[w]here the cytokine has a local
immunostimulatory effect, it can be preferable that it be primarily attached
to the cell membrane to keep it in the vicinity of bystander tumor antigen."
(Hiserodt col. 16, 11. 30-34.)
FF 9. Hiserodt teaches cytokines "that are engineered to incorporate a
region that allows them to be retained in the cell membrane" and that "it is
possible to create a membrane-bound form as a fusion protein." (Hiserodt
col. 7, 11. 36-40 and col. 16, 11. 53-56.)
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Application 12/851,243
ISSUE
Whether a preponderance of the evidence of record supports the
Examiner's conclusion of obviousness under 35 U.S.C. § 103(a).
ANALYSIS
The Examiner concludes that it would have been obvious to one of
ordinary skill in the art at the time of the invention to apply the teachings of
the Known fact to the teachings of Hiserodt to obtain the claimed method of
stimulating an immune response to an antigen. (Final Act. 5.) Furthermore,
according to the Examiner, the person of skill in the art would have had a
reasonable expectation of success because the prior art suggests that
engineered cytokines, wherein a lipid is attached to the cytokine, permits the
complex to become stably associated with the cell membrane. (Id.) In
addition, the Examiner points to Hiserodt' s teaching of the advantage of
using membrane-bound cytokines as opposed to a soluble cytokines. (Id.)
We find that the Examiner has satisfied the burden of showing "some
articulated reasoning with some rational underpinning to support the legal
conclusion of obviousness." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007). Moreover, we agree with the Examiner that all the claimed
elements were known in the prior art, one skilled in the art could have
combined them by known methods with no change in their respective
functions, and that the combination would have yielded predictable results.
(Final Act 5.) See KSR, 550 U.S. at 417 ("[W]hen a patent 'simply arranges
old elements with each performing the same function it had been known to
perform' and yields no more than one would expect from such an
arrangement, the combination is obvious.") (citation omitted). Accordingly,
the Examiner has established a prima facie case of obviousness and, as
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discussed below, Appellant has not overcome or rebutted that prima facie
case.
Membrane Bound GM-CSF
Appellant argues with respect to claims 1 and 20 that Hiserodt only
teaches cytokine secreting cells, and soluble GM-CSP, and not membrane
bound GM-CSP. (Br. 9-10.) Appellant also argues that "there is no
teaching or suggestion in Hiserodt of using a preparation consisting only of
cells and isolated engineered cytokine[ s] for the preparation of an
immunogenic composition." (Id. at 9.)
We are not persuaded. Hiserodt teaches that the cytokine may be
membrane-bound and that "it is possible to create a membrane-bound form
as a fusion protein." (FF 9.) Hiserodt also teaches that cytokines include
GM-CSP, and cytokines that naturally occur in a secreted form "that are
engineered to incorporate a region that allows them to be retained in the cell
membrane." (FF 7, 9.)
Regarding the method of preparing the composition, Appellant argues
Hiserodt separately without addressing the Known fact that is also applied in
the obviousness rejection. The test for obviousness is what the combined
teachings of Hiserodt and the Known fact would have suggested to one of
ordinary skill in the art. See In re Keller, 642 F.2d 413, 425 (CCPA 1981)
(citing cases). Moreover, as the Examiner makes clear, "[i]t would be
immediately obvious to one [of] skill in the art that said engineered
cytokine: (a) is not produced by said cell, and (b) has to be first constructed
and then introduced into the medium comprising the cell, i.e. isolated prior
to formation of the preparation." (Final Act. 4; see also FF 1-5.)
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Activity of Cytokine
Appellant argues with respect to claim 21 that "Hiserodt fails to teach
or suggest preparing an immunogenic composition ... with a cytokine of a
particular activity." (Br. 11.) In particular, Appellant argues that
"[a]lthough there is a general statement in Hiserodt regarding modulation of
cytokine activity ... the immunogenic compositions of Hiserodt include
cytokines produced by cytokine secreting cells, wherein the activity of these
cytokines is not determined prior to formation of the immunogenic
compositions." (Br. 11, citing Hiserodt 19, 11. 3-5.)
We are not persuaded. As discussed above, the teachings of Hiserodt
include membrane-bound cytokines and are not limited to cytokines
produced by cytokine secreting cells. Moreover, in view ofHiserodt's
acknowledged disclosure of the general condition of modulating cytokine
activity, Appellant's claimed ranges of cytokine activity as recited in claim
21 are not entitled to any patentable weight. See In re Aller, 220 F .2d 454,
456 (CCPA 1955) ("[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.").
Amount of Cytokine
Appellant argues with respect to claim 22 that "[t]here is no teaching
or suggestion in Hiserodt of quantitating the amount of cytokine present in
the composition or using a specific amount of cytokine for preparation of the
composition." (Br. 11-12.) We are not persuaded. Hiserodt teaches the
general condition of adjusting the amount of cytokines and cells in the
composition. (Hiserodt 23, 1. 60-24, 1. 7.) Thus, the claimed range of cells
and amount of cytokines recited in claim 22 does not distinguish claim 22 as
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nonobvious over the prior art. See Aller, 220 F .2d at 456; see also Merck &
Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 809 (Fed. Cir. 1989)
("experimentation needed to arrive at the claimed dosages was nothing more
than routine"). Nor has Appellant persuasively established criticality of the
claimed cytokine activity or amounts of cells or cytokines. See Aller, 220
F.2d at 456.
Declaration
Appellants argue the "advantages" of the claimed methods over
Hiserodt with reference to the Young Declaration4 and attached exhibits. 5
(Br. 12-14.) The Young Declaration states that Hiserodt discloses "soluble
GM-CSP and not membrane bound GM-CSP." (Deel. i-fi-f 13 and 20.) The
Young Declaration relies on post-filing6 data regarding (1) "an optimal
amount of GM-CSP" on a cell surface (id. i-f 14), and (2) stability of the
cytokine because engineered GM-CSP "remains bound to the cell surface for
hours and therefore maintains its potency for a long period of time" (id.
i-fi-127-28, Exhibit A). The Young Declaration also includes a statement that
toxicity "is extremely low as compared to soluble GM-CSP" (id. i-f 17), post-
filing data that "soluble GM-CSP enhances tumor growth (id. i-fi-f 18-19,
Exhibits Band C),7 and post-filing data asserted as evidence of the failures
4 Declaration of Elihu Young under 37 C.F.R. § 1.132 dated Jan. 3, 2013
("Young Declaration" or "Deel.").
5 Citations to the respective exhibits may be found at the Evidence Appendix
on page 21 of Appellant's Brief.
6 The present application claims priority to provisional application
60/086,780 filed May 26, 1998. (Spec. 1.)
7 Exhibit C is identified as data generated while Dr. Young was employed at
Genitrix. (Deel. i-f 18.) Exhibit C is undated but the Young Declaration
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of several clinical trials involving secreted GM-CSF (id. iii! 22-26, Exhibits
D, E, and F).
We are not persuaded. The Young Declaration is based on the
incorrect premise that Hiserodt does not disclose membrane bound GM-
CSF. Hiserodt teaches membrane bound GM-CSP (FF 6-9), and the Known
fact establishes that an engineered cytokine can be bound to the cell
membrane (FF 3, 4). Moreover, the mere recognition of latent properties
(i.e. stability or low toxicity) in the prior art does not render nonobvious an
otherwise known invention. See In re Baxter Travenol Labs., 952 F.2d 388,
392 (Fed. Cir. 1991). Furthermore, the argument that soluble or secreted
GM-CSP was ultimately proven to be ineffective is not persuasive because
membrane bound GM-CSP is taught by Hiserodt. 8
Unexpected Results
Appellant refers to the "data presented in the declaration" as
demonstrating the following "surprising and unexpected advantages" over
Hiserodt:
(1) the level of GM-CSP bound to the surface of the cells used
for the method of the invention can be titrated and can therefore
be used to prepare vaccines of varied potency (2) GM-CSP
remains bound to the surface of the cells for extended periods of
time and can therefore be used for vaccines with a high potency
as compared to soluble GM-CSP which diffuses away; and (3)
indicates that Dr. Young was employed by Genitrix from November 1997
through QI of 2008. (Id. if 4.)
8 Because we find the Young Declaration unpersuasive, we need not
determine whether post-filing data can be relied on by Appellant. Cf
Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 976
(Fed. Cir. 2014), reh 'g denied, 769 F.3d 1339 (Fed. Cir. 2014).
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the cells provide for vaccines with significantly decreased
toxicity as compared to soluble GM-CSP.
(Br. 14--15; Deel. i-f30.)
Appellant also quotes from the Specification to argue "the surprising
and unexpected discovery" and "surprising advantages" arising from the use
of a membrane-bound cytokine as opposed to a soluble cytokine. (Br. 15.)
Appellant also argues that "there is no predictable expectation of success of
arriving at the claimed invention by using a cell that expresses a membrane-
bound GM-CSP in an unregulated manner." (Id.)
We are not persuaded. Unexpected results must be shown to be
unexpected compared with the closest prior art, and, again, the "[m]ere
recognition of latent properties in the prior art does not render nonobvious
an otherwise known invention." Baxter, 952 F.2d at 392. Moreover,
unexpected results must be established by factual evidence, and "[m]ere
argument or conclusory statements in the specification does not suffice." In
re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (quoting In re De Blauwe,
736 F.2d 699, 705 (Fed. Cir. 1984)).
Here, neither the Young Declaration nor the Specification compares
the efficacy of vaccines comprising membrane bound GM-CSP (e.g., as
taught by Hiserodt) with the claimed invention. (See Ans. 7.) The ability to
titrate cytokines and optimize the amount of GM-CSP on a cell surface
would not have been unexpected based on the Known fact and teachings of
Hiserodt regarding cytokine potency. (FF 2-5; Hiserodt 23, 1. 60-24, 1. 7.)
Moreover, Appellant does not persuasively establish that the asserted
stability and decreased toxicity are other than latent properties of the prior
art, and Appellant's arguments are otherwise insufficient to overcome the
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prima facie case, including the reasonable expectation of success as set forth
by the Examiner. (Final Act. 5.)
Motivation/Hindsight
Appellant argues that "the Examiner has not supplied any motivation
to combine the references ... any such motivation to combine the references
in this manner is unsupported and draws on impermissible hindsight." (Br.
15.) We are not persuaded. Hiserodt expressly teaches the preferred use of
a membrane bound cytokine. (FF 8.) Moreover, evaluating suggestion or
motivation in an obviousness analysis "not only permits, but requires,
consideration of common knowledge and common sense." DyStar
Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d
1356, 1367 (Fed. Cir. 2006). Here, the Examiner makes clear that the
motivation for combining the Known fact with Hiserodt includes "common
knowledge." (Final Act. 3.) Furthermore, the Examiner points to specific
disclosures in the prior art (see, e.g., FF 8) that give a reason or motivation
for the claimed invention, thereby overcoming any concern regarding
hindsight bias. See Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280,
1292 (Fed. Cir. 2012).
CONCLUSION
A preponderance of evidence of record supports the Examiner's
conclusion that claims 1 and 20-22 are obvious under 35 U.S.C. § 103(a).
Claims 3, 4, 10-18, and 23 were not argued separately and fall with claim 1.
SUMMARY
We affirm the rejection of all claims on appeal.
TIME PERIOD FOR RESPONSE
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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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