Ex Parte Friedlander et al

Patent Trial and Appeal Board

Dec 16, 2016

12952910 (P.T.A.B. Dec. 16, 2016)

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.
12/952,910 11/23/2010 Martin FRIEDLANDER TSRI 988.1 Div.l 2563
2387 7590 12/16/2016
Olson & Cepuritis, LTD.
20 NORTH WACKER DRIVE
36TH FLOOR
CHICAGO, IL 60606
EXAMINER
NGUYEN, QUANG
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
12/16/2016 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 MARTIN FRIEDLANDER, ATSUSHI OTANI,
KAREN DA SILVA, and STACEY (HANEKAMP) MORENO
Appeal 2014-007938
Application 12/952,910
Technology Center 1600
Before JEFFREY N. FREDMAN, TIMOTHY G. MAJORS, and
KRISTI L. R. SAWERT, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35U.S.C. § 134 involving claims to a
transfected lineage negative hematopoietic stem cell population. The
Examiner rejected the claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
“Age related macular degeneration (ARMD) and diabetic retinopathy
(DR) are the leading causes of visual loss in industrialized nations and do so
1 Appellants identify the Real Party in Interest as The Scripps Research
Institute (see App. Br. 1).
Appeal 2014-007938
Application 12/952,910
as a result of abnormal retinal neovascularization” (Spec. 2:16—18). The
“lineage negative hematopoietic stem cell (HSC) population has recently
been shown to contain endothelial progenitor cells (EPC) capable of forming
blood vessels in vitro and in vivo .... These cells can participate in normal
and pathological postnatal angiogenesis” (Spec. 3:1—5).
“The Lin' HSC populations of the present invention include
endothelial progenitor cells (EPC), also known as endothelial precursor
cells, that selectively target activated retinal astrocytes when intravitreally
injected into the eye” (Spec. 3:28 to 4:2). “The isolated, Lin' HSC
populations of the present invention can be used to rescue and stabilize
degenerating retinal vasculature in mammals, to rescue neuronal networks,
and to facilitate repair of ischemic tissue” (Spec. 4:20-23).
The Claims
Claims 16, 21, and 33 are on appeal. Independent claim 21 is
representative and reads as follows:
21. A transfected lineage negative hematopoietic stem cell
population prepared by:
(a) extracting bone marrow from an adult mammal;
(b) separating a plurality of monocytes from the bone marrow;
(c) labeling the plurality of monocytes with biotin-conjugated
lineage panel antibodies to one or more lineage surface antigens
selected from the group consisting of CD2, CD3, CD4, CD11, CD1 la,
Mac-1, CD 14, CD 16, CD19, CD24, CD33, CD36, CD38, CD45, Ly-
60, TER-119, CD45RA, CD56, CD64, CD68, CD86, CD66b, HLA-
DR, and CD235a;
(d) separating monocytes that are positive for said one or more
lineage surface antigens from the plurality of monocytes and
recovering a population of lineage negative hematopoietic stem cells
containing endothelial progenitor cells; and
2
Appeal 2014-007938
Application 12/952,910
(e) transfecting the lineage negative hematopoietic stem cells
recovered in step (d) with a polynucleotide that operably encodes an
anti-angiogenic peptide.
The Issue
The Examiner rejected claims 16, 21, and 33 under 35 U.S.C. § 103(a)
as obvious over Emerson,2 Wilson,3 and Schimmel4 (Final Act. 4—8).
The Examiner finds Emerson teaches “preparation of a genetically
modified human hematopoietic stem cell population isolated from adult bone
marrow that are lineage negative and transfected with a recombinant
retrovirus encoding any desired gene product” (Final Act. 5). The Examiner
finds Emerson teaches “bone-marrow derived lineage negative
hematopoietic stem cells were prepared by . . . incubating mononuclear cells
with . . . antibodies that recognize committed progenitor cells (e.g., anti-
CD33), and the removal of the mature cells prior to the recombinant
retrovirus infection” (id.).
The Examiner acknowledges that Emerson does not “teach that their
bone marrow derived lineage negative hematopoietic stem cell population is
transfected with a gene encoding a therapeutically useful peptide which is an
anti-angiogenic peptide or an anti-angiogenic protein fragment, or T2-TrpRS
with the sequence of SEQ ID NO: 2” (Final Act. 6; emphasis omitted).
The Examiner finds that Wilson teaches “lineage negative stem cell
populations include a CD34+Lin-FGFR+ cell population having 96%, 97%
2 Emerson et al., US 5,670,351, issued Sept. 23, 1997 (“Emerson”).
3 Wilson et al., US 6,767,737 Bl, issued July 27, 2004 (“Wilson”).
4 Schimmel et al., US 2003/0017564 Al, published Jan. 23, 2003
(“Schimmel”).
3
Appeal 2014-007938
Application 12/952,910
and 37% of the cells positive for CD31, CD117 and TIE1” and that “the
stem cell populations can be used to target the delivery of angiostatic agents
and anti-tumor agents to the rapidly proliferating vascular bed associated
with tumors” (Final Act. 6; emphasis omitted).
The Examiner finds Schimmel teaches “truncated Tryptophanyl-tRNA
synthetase (TrpRS) polypeptides . . . 100% identical to SEQ ID NO: 2 . . .
are potent polypeptides for the inhibition of angiogenesis”; that “cells can be
transfected in vivo, ex vivo or in vitro with their recombinant vectors”; and
that “angiostatic TrpRS therapy can be used ... to prevent further growth or
even regress solid tumors, since angiogenesis and neovascularization are
essential steps in solid tumor growth” (Final Act. 7; emphasis omitted).
The Examiner finds it obvious to
modify the teachings of Emerson et al. by also transfecting their
bone marrow derived lineage negative hematopoietic stem cell
population with a gene encoding a therapeutically useful
peptide that is an anti-angiogenic peptide or an anti-angiogenic
protein fragment, or T2-TrpRS with the sequence of SEQ ID
NO: 2 to target/deliver these potent angiostatic peptides to the
rapidly proliferating vascular bed associated with tumors to
inhibit the growth of solid tumors in light of the teachings of
Wilson et al and Schimmel et al.
(Final Act. 7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the prior art render the claims
obvious?
4
Appeal 2014-007938
Application 12/952,910
Findings of Fact
1. Emerson teaches “novel methods, including culture media
conditions, for the ex vivo replication and stable genetic transformation of
human stem cells” (Emerson 7:25—27).
2. Emerson teaches “hematopoietic stem cell concentration may
be increased as follows. Red blood cells are removed from a bone marrow
aspirate . . . antibodies are included which recognize committed progenitor
cells (including anti CD 33). The mature cells are then removed by one of
various procedures including panning, magnetic beads” (Emerson 23:64 to
24:57).
3. Emerson teaches “[hjuman bone marrow cells were obtained
following informed consent from heparinized aspirates of the iliac crest bone
marrow” (Emerson 34:49—51).
4. Emerson teaches “[ljineage negative (Lin') selection of bone
marrow cells . . . [mjature mononuclear cells were removed from the above
cell preparation by incubating the cells with a mixture of monoclonal
antibodies” (Emerson 34:60-64).
5. Emerson teaches that “retroviral producer cell lines . . . produce
amphotrophic viral particles that contain the NEO gene . . . providing
resistance to the mammalian neomycin analog G418” (Emerson 36:2—7).
6. Emerson teaches “hematopoietic cells prepared above were
added to the irradiated viral producer cells . . . [cjells removed from the
cultures were plated in methylcellulose with G418” (Emerson 37:2—39).
7. Emerson teaches “progenitor cells that were clonable to
hematopoietic colonies survived exposure to G418. This indicates that these
5
Appeal 2014-007938
Application 12/952,910
progenitor cells had been rendered G418 resistant by virtue of containing the
G418 resistance gene transferred by the retrovirus to stem cells” (Emerson
38:1-5).
8. Wilson teaches that by “isolating FGFR+ primitive phenotype
cells, preferably CD34+FGFR+ or CD34'lin'FGFR+, from other cells in the
body, it is possible to obtain relatively pure stem cells, preferably separate
from contaminating cells and other substances, so that the stem cells can be
safely transplanted into a patient” (Wilson 4:30—35).
9. Wilson teaches the “pluripotent FGFR+ primitive phenotype
stem cells . . . have considerable commercial use, including ... to target the
delivery of angiostatic agents and anti-tumor agents to the rapidly
proliferating vascular bed associated with tumors” and as “vectors for
genetic engineering” (Wilson 9:1—26).
10. The Examiner finds that “Schimmel et al already disclosed that
truncated Tryptophanyl-tRNA synthetase (TrpRS) polypeptides (e.g., mini
TrpRS, T1 and T2), including the polypeptide with SEQ ID NO: 7 that is
100% identical to SEQ ID NO: 2 of the present invention” (Final Act. 7; cf.
Spec. Fig. 8 and SEQ ID NO: 2 and Schimmel 30, SEQ ID NO: 7).
11. Schimmel teaches “[ajngiostatic trpRS therapy can be used to
oppose the angiogenic activity of endogenous and exogenous angiogenic
factors, and to prevent the further growth or even regress solid tumors, since
angiogenesis and neovascularization are essential steps in solid tumor
growth” (Schimmel 1132).
12. Schimmel teaches “viral and non-viral methods suitable for
introduction of a nucleic acid molecule into a target cell” (Schimmel 1116)
6
Appeal 2014-007938
Application 12/952,910
and that the “cells can be transfected as primary cells isolated from a patient
. . . [fallowing ex vivo or in vitro transfection, the cells can be implanted
into a host” (Schimmel 1121).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Inti Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Mat417.
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 4—8; FF 1—12). We address
Appellants’ arguments below.
Appellants contend the “Examiner has failed to meet the burden of
establishing why one of ordinary skill in the art would have been motivated
to combine the cited references, thus the obviousness rejection cannot be
maintained” (App. Br. 5).
We do not find this argument persuasive because the Examiner
reasons that:
it would have been obvious for an ordinary skilled artisan to
modify the teachings of Emerson et al. by also transfecting their
bone marrow derived lineage negative hematopoietic stem cell
population with a gene encoding a therapeutically useful
peptide that is an antiangiogenic peptide or an anti-angiogenic
protein fragment, or T2-TrpRS with the sequence of SEQ ID
NO: 2 to target/deliver these potent angiostatic peptides to the
rapidly proliferating vascular bed associated with tumors to
7
Appeal 2014-007938
Application 12/952,910
inhibit the growth of solid tumors in light of the teachings of
Wilson et al and Schimmel et al.
(Ans. 7).
We agree with the Examiner because Emerson and Wilson both teach
transfection of lineage negative hematopoietic stem cells with heterologous
nucleic acids (FF 1—8), Wilson specifically suggests “delivery of angiostatic
agents and anti-tumor agents to the rapidly proliferating vascular bed
associated with tumors” (FF 9), and Schimmel teaches delivery of anti-
angiogenic peptides “to prevent the further growth or even regress solid
tumors” (FF 11) by transfection of extracted primary cells for reimplantation
into the patient (FF 12).
The ordinary artisan, interested in achieving Schimmel’s goal of
treating tumors with anti-angiogenic peptides by ex vivo gene therapy (FF
11—12), would have reasonably obtained hematopoietic stem cells as taught
by Emerson and Wilson because Wilson teaches “pluripotent FGFR+
primitive phenotype stem cells . . . have considerable commercial use,
including ... to target the delivery of angiostatic agents” (FF 9). “[A]ny
need or problem known in the field of endeavor at the time of invention . . .
can provide a reason for combining the elements in the manner claimed.”
KSR, 550 U.S. at 420.
Appellants contend that “Wilson clearly is an inapposite reference.
The Examiner has failed to identify any teaching in Emerson that would
have led one of ordinary skill to the Wilson reference. There has been no
showing that the cell population obtained by Emerson from the bone marrow
aspirate is the same as the unique stem cell population described by Wilson”
8
Appeal 2014-007938
Application 12/952,910
(App. Br. 5). Appellants contend the “Examiner has failed to show why one
of ordinary skill would have had any reason to substitute the stem cell
population of Emerson for the unique FGFR+ primitive phenotype cell
population isolated by Wilson” (App. Br. 6).
We are not persuaded. Both Wilson and Emerson are drawn to ex
vivo replication of hematopoietic stem cells for stable genetic transformation
(FF 1, 8) and Wilson teaches that one type of agent useful in such cells are
angiostatic agents (FF 9). By any test, Wilson, Emerson, and Schimmel are
analogous to one another as drawn to ex vivo gene therapy materials and
processes and are pertinent to those interested in performing ex vivo gene
therapy because all three of these references discuss transforming cells ex
vivo and returning them to patients (FF 1—12). See In re Wood, 599 F.2d
1032, 1036 (CCPA 1979). Moreover, “[n]on-obviousness cannot be
established by attacking references individually where the rejection is based
upon the teachings of a combination of references.” In re Merck & Co., 800
F.2d 1091, 1097 (Fed. Cir. 1986).
Appellants contend that:
Schimmel, however, does not suggest to one of ordinary skill
that a stem cell population, or the stem cell populations of
Emerson or Wilson, should be or could be transfected by a
polynucleotide that encodes T2-TrpRS or by other anti-
angiogenic peptide, or that such transfection could be
implemented with a reasonable expectation of success. The
cited Paragraph [0121] of Schimmel would not have led one of
ordinary skill to such a conclusion. Gene therapy clearly is an
unpredictable art, and such unpredictability necessarily favors
non-obviousness.
(App. Br. 6).
9
Appeal 2014-007938
Application 12/952,910
We are not persuaded because paragraph 116 of Schimmel suggests
transfecting nucleic acids into cells, paragraph 132 of Schimmel suggests
angiostatic nucleic acids and paragraph 121 of Schimmel expressly teaches
“cells can be transfected as primary cells isolated from a patient. . .
[fallowing ex vivo or in vitro transfection, the cells can be implanted into a
host” (FF 11—12). The ordinary artisan, familiar with Schimmel, would
have reasonably looked to other prior art teaching isolation methods of
primary cells that are useful in gene therapy such as those of Emerson and
Wilson as discussed by the Examiner (see Final Act. 7).
“Responding to concerns about uncertainty in the prior art influencing
the purported success of the claimed combination, this court [in O’Farrell]
stated: ‘[ojbviousness does not require absolute predictability of success . . .
all that is required is a reasonable expectation of success'1'’'’ In re Kubin, 561
F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O Farrell, 853 F.2d 894, 903—
904 (Fed. Cir. 1988). The instant references are all patent documents that
are presumed enabled. “[A] prior art publication cited by an examiner is
presumptively enabling barring any showing to the contrary by a patent
applicant.” In re Antor Media Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012).
Appellants have provided no such showing that the prior art is not enabled.
We recognize, but find unpersuasive, Appellants contention that “US
2002/0061587 by Anversa, newly applied, does not provide a nexus between
Emerson and Wilson” (Reply Br. 2). Because we have already concluded
that Emerson, Wilson, and Schimmel (the references relied upon for the
10
Appeal 2014-007938
Application 12/952,910
rejection) render the claims obvious, we do not rely upon An versa5 and need
not address this further evidence showing isolation of hematopoietic stem
cells for gene therapy was known.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
prior art render the claims obvious.
SUMMARY
In summary, we affirm the rejection of claims 16, 21, and 33 under
35 U.S.C. § 103(a) as obvious over Emerson, Wilson, and Schimmel.
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
5 Anversa, P., US 2002/0061587 Al, published May 23, 2002 (“Anversa”).
11