Ex Parte Cunningham-Rundles et al

Patent Trial and Appeal Board

Jan 29, 2019

12688160 (P.T.A.B. Jan. 29, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/688, 160 01/15/2010
23389 7590 01/31/2019
SCULLY SCOTT MURPHY & PRESSER, PC
400 GARDEN CITY PLAZA
SUITE 300
GARDEN CITY, NY 11530
FIRST NAMED INVENTOR
Susanna Cunningham-Rundles
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.
23761 (4199-03-US) 2998
EXAMINER
PYLA,PAULD
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
01/31/2019 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):
Docket@SSMP.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SUSANNA CUNNINGHAM-RUNDLES and
HONG LIN SMITH-JONES
Appeal2017-004357
Application 12/688,160
Technology Center 1600
Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.
KATZ, Administrative Patent Judge.
DECISION ON APPEAL
Appeal2017-004357
Application 12/688,160
Appellants 1 seek our review, under 35 U.S.C. § 134(a), of the
Examiner's decision to reject claims 18, 23, 27, 32, 43, and 44. 2 We have
jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.
Appellants' Specification is directed to using B-glucans, a component
of the cell walls of yeasts, fungi, and bacteria, to expand hematopoietic
progenitor cells, which can then be used for homing3 and engrafting4 to the
bone marrow of a transplantation recipient. The Specification also explains
that B-glucans can ameliorate the toxic effects of chemotherapy, while
promoting development of neutrophils and their functional activity. (See
Spec. 1: 18-22.) Appellants focus on a specific B-glucan derived from
maitake mushrooms ("MBG") in their claims.
Appellants' claim 18 recites 5 :
A method of promoting homing of a population of cells
which comprises hematopoietic progenitor and/or stem cells
obtained from an umbilical cord blood sample from a donor
mammal to the bone marrow of a recipient mammal,
compnsmg
orally administering a beta glucan composition, wherein
said beta glucan composition is the D-fraction extracted from
1 Appellants report that the real party in interest is Cornell University.
(Appeal Brief filed July 5, 2016 ("App. Br.") 2.)
2 Appellants report that claims 1-18, 22-24, 27, 31-33, and 36-44 are
pending, but that claims 1-17, 22, 24, 31, 33, and 36-42 have been
withdrawn from consideration. (App. Br. 4.)
3 Appellants' Specification defines "'homing"' as the ability of the
transplanted cells to find their way to locate to bone marrow of the recipient.
(Specification ("Spec.") 14:27-28.)
4 Appellants' Specification defines "'engraftment"' as the ability of
transplanted cells to integrate or insert into the bone marrow of the recipient.
(Spec. 15:4--5.)
5 Indentations added for clarity.
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maitake mushroom and characterized by a 1, 6 main chain with
1,3 branches, and separately administering said population of
cells to said recipient mammal.
(App. Br. 27, Claims App'x.) Appellants' independent claim 27 recites a
method that is the same as the method recited in claim 18, but it is a method
of "promoting engraftment of a population of cells which comprises
hematopoietic progenitor and/or stem cells obtained from an umbilical cord
blood sample from a donor mammal to the bone marrow of a recipient
mammal" instead of a method of "homing" of a population of the same cells.
(See App. Br. 27, Claims App'x (emphasis added).)
The Examiner rejected independent claims 18 and 27, as well as
claims 23 and 32, which depend from them, under 35 U.S.C. § 103(a) as
being obvious over Patchen, 6 Lin,7 and Nanba, 8 as evidenced by Tanavde. 9
(Examiner's Answer issued November 15, 2016 ("Ans.") 3-9.) The
Examiner also rejected claims 18, 23, 27, and 32 under 35 U.S.C. § 103(a)
as being obvious over Cramer, 10 Lin, and Nanba, as evidenced by Tanavde.
(Ans. 11-19.)
6 Patchen and Bleicher, US Patent No. 6,117,850, issued September 12,
2000.
7 Lin et al., Enhancement of Umbilical Cord Blood Cell Hematopoiesis by
Maitake Beta-Glucan Is Mediated by Granulocyte Colony-Stimulating
Factor Production, 14 Clinical and Vaccine Immunology 21-27 (2007).
8 Nanba and Kubo, US Patent No. 5,854,404, issued December 29, 1998.
9 Tanavde et al., Human stem-progenitor cells from neonatal cord blood
have greater hematopoietic expansion capacity than those from mobilized
adult blood, 30 Experimental Hematology 816-823 (2002).
1° Cramer, et al., f]-Glucan enhances complement-mediated hematopoietic
recovery after bone marrow injury, 107 Blood 835-840 (2006).
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Application 12/688,160
The Examiner rejected dependent claims 43 and 44 under 35 U.S.C.
§ 103(a) as being obvious over Patchen, Lin, and Nanba, as evidenced by
Tanavde, and also in view ofKerre 11 (Ans. 9-11) or, alternatively, as being
obvious over Cramer, Lin, Nanba, as evidenced by Tanavde, and Kerre (id.
at 18-19).
Appellants do not argue for the separate patentability of any of the
claims recited in these rejections.
Findings of Fact
1. Patchen teaches that methods for "enhancing or facilitating
hematopoietic reconstitution or engraftment, by the administration of an
underivatized, aqueous soluble B(l,3)-glucan." (Patchen 1:65-2:1; see also
abstract.)
2. Patchen teaches that the methods can be used to increase the
number of engrafted cells, to decrease the time to engraftment, or to enhance
the quality of engraftment in hematopoietic reconstitution. (See Patchen
2:27-30.)
3. Patchen teaches that aqueous soluble B(l,3)-glucan can be
administered to the patient at the time of autologous transplant to facilitate
the reconstitution ofhematopoietic progenitor cells. (Patchen 5:42--45.)
4. Patchen includes Example 11, which provides for administering
underivatized, aqueous soluble B(l ,3)-glucan to the patient at the time of
11 Kerre et al., Both CDJ4+3s+ and CDJ4+3s- Cells Home Specifically to the
Bone Marrow of NOD/LtSZ scid/scid Mice but Show Different Kinetics In
Expansion, 167 The Journal of Immunology 3692-3698 (2001).
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autologous transplant to facilitate reconstitution of the patient's
hematopoietic progenitor cells. (See Patchen 10:4--14.)
5. Patchen does not teach promoting the homing or engraftment of
umbilical cord blood sample cells or using B(l,3)-glucan with 1,6 main
chain with 1,3 branches maitake mushroom extract.
6. Lin teaches that umbilical cord blood cells are increasingly used
for stem cell transplantation for the treatment of leukemia. (See Lin 21.)
7. Lin teaches that maitake B-glucan ("MBG") enhances human
umbilical cord blood cell proliferation and differentiation. (See Lin 21.)
8. Lin states that the results reported raise the possibility that
MBG could enhance the expansion of umbilical cord blood cells ex vivo to
improve engraftment. (See Lin 21.)
9. Tanavde teaches that neonatal (umbilical) cord blood
preparations generated massively increased in vitro assessed hematopoietic
capacity and maintained engraftment potential compared to peripheral blood
stem cells, which generated less in vitro assessed hematopoietic capacity and
decreased engraftment potential. (Tanavde abstract.)
10. Nanba teaches that it was known that polysaccharides
consisting of B-1, 6-linked glucose main chain with B-1,3-linked glucose
branches, as well as B-1,3-linked glucose main chain with B-1,6-linked
glucose branches, extracted from the fruit bodies of Grifola (maitake)
mushrooms have anticancer activity. (See Nanba 1:11-15.)
11. Nanba teaches extracting antitumor substances with
immunopotentiating activity from Grifola. (Nanba 1 :38--42.)
12. Nanba teaches that the substance obtained by the invention is of
low toxicity and high safety and can be administered orally in foods and
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Application 12/688,160
pharmaceutical preparations, especially antitumor agents as tablets, capsules,
liquids, or syrups. (See Nanba 4:34--38.)
13. Cramer teaches the effect of orally administered whole glucan
particles (such as B-glucan) on the repopulation of bone marrow in lethally
irradiated mice following hematopoietic transplantation. (Cramer 838.)
14. Cramer teaches that mice treated with B-glucan after irradiation
and subsequent hematopoietic transplantation had approximately 40% more
day-12 colony forming unit-S colonies in the spleen compared with mice
without B-glucan treatment. (Cramer 838).
15. Cramer teaches that CR3, the binding site of B-glucan, may
contribute to early engraftment ofhematopoietic cells. (See Cramer 838.)
16. Cramer teaches that yeast B-glucan may assist in the
engraftment of hematopoietic cells and the acceleration of hematopoietic
function following allogenic hematopoietic transplantation. (See Cramer
840.)
Analysis
Rejection over Patchen, Lin, Tanavde, and Nanba
The Examiner determines that it would have been obvious to one of
ordinary skill in the art to substitute hematopoietic stem progenitor cells and
bone marrow cells in the methods of Patchen with umbilical cord cells,
because Lin and Tanavde teach that umbilical cord cells can be used for
stem cell transplantation and expand well ex vivo. (See Ans. 6-7; see FFs 6-
9.) The Examiner also determines that a person of ordinary skill in the art
would have been motivated to substitute the MBG composition from Lin or
Nanba for B-glucan composition of Patchen, because Lin and Nanba teach
that MBG is widely known to treat cancer and can be administered orally to
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activate antitmnor response through effects on the immune system. (See
Ans. 7-8; FFs 7, 8, and 10-12.) The Examiner determines further that a
person of ordinary skill in the art at the time would have used the MBG
composition with 1,6 main chain and 1,3 branches taught in Nanba because
it was known to enhance murine bone marrow cell proliferation and
differentiation and for using progenitor and stem cells in cancer therapies.
(Ans. 7-8.)
Appellants argue that the Examiner erred in rejecting claims 18, 23,
27, and 32 as being obvious over Patchen, Lin, and Nanba, as evidenced by
Tanavde because the skilled artisan would not have considered Patchen to
teach that oral administration of beta glucan promotes cell homing and
engraftment. (See App. Br. 9-11; see Reply Brief filed January 17, 2017
"Reply Br." 2.) Rather, Appellants argue, a skilled artisan would have
understood that Patchen teaches mobilization of bone marrow cells into the
blood for collection and saving the stem/progenitor cells for re-transfusion
back into the subject after chemotherapy. (See App. Br. 10.)
We are not persuaded by Appellants' argument because, in addition to
teaching that administration of B-glucan promotes mobilization, Patchen also
teaches in Example 11, and in other passages, administering B-glucan "at the
time of autologous transplant to facilitate the reconstitution of hematopoietic
progenitor cells." (Patchen 10:8-12, Example 11; see Ans. 4; see also Final
Office Action issued October 5, 2015 at 4.) We do not disagree with
Appellants that mobilization of cells in the bone marrow is a separate and
distinct process from homing or engraftment (see App. Br. 10), but
Appellants do not address Example 11 and other portions of Patchen that
discuss the effects of B(l ,3)-glucan on reconstitution of hematopoietic cells
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in their arguments. (See, e.g., Patchen 1 :65----67 ("The invention further
relates to methods for enhancing or facilitating hematopoietic reconstitution
or engraftment, by the administration of an underivatized, aqueous soluble
B(l,3)-glucan.").) We are not persuaded, as Appellants argue, that Patchen
teaches only an effect that is opposite to the effect of the claimed methods.
(See App. Br. 10.)
We are also not persuaded that Appellants' claimed methods are
nonobvious because the mobilization methods of Patchen requires
intravenous injection of B-glucan, not oral delivery. (See App. Br. 12.)
According to Appellants, the teaching in Patchen that B-glucan can be
administered by many different routes refers only to mobilization protocols
because the summary of the invention and Examples 1-10 are directed to
mobilization. (See id.)
However, immediately prior to teaching that B-glucan can be
administered by many routes, Patchen states: "The underivatized, aqueous
soluble B(l ,3)-glucan is administered to an animal or a human in an effective
amount, sufficient to mobilize [peripheral blood precursor cells], to elevate
the level of circulating [peripheral blood precursor cells] or facilitate
hematopo ietic reconstitution." (Patchen 4: 3 9--4 2 ( emphasis added).)
Patchen continues by referring to dosing regimens and then to oral
administration along with other routes. (See Patchen 4:43----60.) Thus, we do
not agree with Appellants that reference to oral administration is specific
only to mobilization; instead, we understand that it also refers to
hematopoietic reconstitution. Because Patchen teaches enhancing or
facilitating hematopoietic reconstitution or engraftment, we are not
persuaded that this element renders Appellants' claims non-obvious.
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Appellants argue that Lin teaches using MBG to expand umbilical
cord cells in vitro and that it was only conjecture and hindsight construction
by the Examiner to conclude that there would have been a reasonable
expectation of success using MBG with the in vivo methods of Patchen.
(See App. Br. 16-17.) We are not persuaded by Appellants' argument
because the conclusions stated in Lin indicate a reasonable expectation that
the in vitro results might be successfully applied to other settings. Lin
states: "the results support the possibility that MBG could enhance the
expansion of [ cord blood] cells ex vivo to improve engraftment." (Lin 21.)
Thus, the conclusions recited in Lin support the Examiner's determination.
Appellants also argue that the activity of B-glucan is highly
unpredictable, wherein B-glucan derived from different sources, for example
fungi or yeast, can have significantly different effects in vivo. (See App. Br.
17-20; see Reply Br. 3.) Appellants cite to Driscoll, 12 arguing that yeast-
derived B-glucan exhibits stronger anti-tumor activity than fungus-derived B-
glucan. (See App. Br. 17 .) Appellants also cite to Hishida 13 to argue that B-
glucans from mushroom fruit bodies were inactive when administered
orally, but had anti-tumor effects when administered intraperitoneally or
intravenously. (See App. Br. 17-18.) Appellants argue that Nanba teaches
only in vitro experiments and intraperitoneal injection of glucan/protein
12 Driscoll et al., Therapeutic potential of various /J-glucan sources in
conjunction with anti-tumor monoclonal antibody in cancer therapy, 8
Cancer Biology & Therapy 218-225 (2009).
13 Hishida et al., Antitumor Activity Exhibited by Orally Administered
Extract from Fruit Body of Grifola frondosa (Maitake), 36 Chem. Pharm.
Bull 1819-1827 (1988).
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complexes to demonstrate immunopotentiating and anti-cancer activity.
(See App. Br. 18.)
Because the results in Lin "support the possibility that MBG could
enhance the expansion of [ cord blood] cells ex vivo to improve engraftment"
(Lin 21 ), we are not persuaded by Appellants' argument. Lin expressly
suggests using MBG ex vivo, even though the actual results it reports are
from in vitro studies. Lin also reports that "MBG administered orally
activates the host antitumor response through effects on the immune system
rather than by direct cytostatic or cytotoxic effects on tumor cells." (Lin 21.)
Furthermore, even though B-glucans from different sources can have
different effects, as indicated by Driscoll and Hishida, Lin addresses the
specific B-glucan recited in Appellants' claims. (See Ans. 25.) Accordingly,
we are not persuaded that one of ordinary skill in the art would not have
looked to MBG for oral administration to promote homing and engraftment
of umbilical cord blood cells.
Appellants argue that "[ a ]gainst the unpredictability in the art ... the
results achieved by this present invention are unexpected." (App. Br. 19; see
also Reply Br. 5.) Appellants cite to page 11, lines 23-28 to page 12, lines
1-24 and Figures 3-5 of their Specification. (See App. Br. 19.) Although
Figures 3-5 provide results comparing treatment with MBG and without,
pages 11 and 12 do not discuss results, but rather the sources and
composition of materials. Appellants do not direct us to, and we do not find,
discussion characterizing of the results shown in Figures 3-5 as being
unexpected. Instead, Appellants' argument is merely unsupported attorney
argument, to which we accord little probative value. See In re Geisler, 116
F.3d 1465, 1470 (Fed. Cir. 1997) (holding that attorney arguments and
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conclusory statements that are unsupported by factual evidence are entitled
to little probative value.
Appellants do not persuade us that the Examiner erred in rejecting
claims 18, 23, 27, and 32 as being obvious over Patchen, Lin, and Nanba, as
evidenced by Tanavde.
Rejection over Cramer, Lin, Tanavde, and Nanba
Cramer teaches that yeast B-glucan may assist in the engraftment of
hematopoietic progenitor cells and the acceleration ofhematopoietic
function following allogeneic transplant. (See Cramer 840; FFs 13-16; see
Ans. 13.) The Examiner determines that because Lin, as further evidenced
by Tanavde, indicates umbilical cord cells were used for stem cell
transplantation, it would have been obvious to those of ordinary skill in the
art at the time to substitute the hematopoietic progenitor cells used in
Cramer with umbilical cord blood cells. (See Ans. 15-16.) The Examiner
also determines that a person of ordinary skill in the art would have
substituted the B-glucan used in Cramer with the MBG taught in Lin and
N anba because MBG was known to be a useful cancer treatment and
enhances murine bone marrow cell proliferation and differentiation. (Ans.
16-17.)
Appellants argue that Cramer teaches using B-glucans distinct from
those claimed. (See App. Br. 21.) We are not persuaded by this argument
because it does not address the Examiner's entire rejection, which includes
citations to Lin and Nanba showing that maitake B-glucan characterized by a
1,6 main chain with 1,3 branches was suggested to enhance the expansion of
umbilical cord blood cells ex vivo to improve engraftment. (See Ans. 5.)
"Non-obviousness cannot be established by attacking references individually
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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 also argue that Driscoll teaches away from substituting the
whole glucan particles ("WGP") used in Cramer with the MBG taught in Lin
and Nanba because Driscoll teaches that yeast-derived B-glucan WGP have
much stronger adjuvant activity compared to mushroom B-glucans with
respect to anti-cancer activity. (See App. Br. 22, citing Driscoll 219.) We
are not persuaded by this argument because the portion of Driscoll cited by
Appellants refers to adjuvant activity of B-glucans when used in
combination with a monoclonal antibody to achieve tumor regression.
Appellants do not claim adjuvant activity of B-glucan.
Appellants do not persuade us that the Examiner erred in rejecting
claims 18, 23, 27, and 32 as being obvious over Cramer, Lin, and Nanba, as
evidenced by Tanavde.
Rejections of Claims 43 and 44
The Examiner rejected claims 43 and 44 as being obvious over either
Patchen or Cramer, Lin, Nanba, and Kerre in view of Tanavde. (See Ans. 9--
11 and 18-19.) Claims 4 3 and 44 depend from claims 18 and 2 7,
respectively, and require the population of cells obtained from the umbilical
cord blood to be administered to the recipient without in vitro expansion.
(See App. Br. 28, Claims App'x.) The Examiner cites Kerre for teaching
injection of umbilical cord blood cells into a recipient mouse within 24
hours of collection, without in vitro expansion. (See Kerre 3693; see Ans.
10.)
Appellants argue that Kerre does not teach oral administration of any
B-glucan and does not alleviate the deficiencies of the combination of
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Patchen, Lin, and Nanba or of Cramer, Lin, and Nanba. (See App. Br. 23.)
Because, as explained above, we are not persuaded that there are
deficiencies in the combination of Patchen or Cramer, Lin, and Nanba,
Appellants have not persuaded us that the Examiner's rejection of claims 43
and 44 is an error.
Appellants do not persuade us that the Examiner erred in rejecting
claims 43 and 44 as being obvious over Patchen or Cramer, Lin, Nanba, and
Kerre, as evidenced by Tanavde.
Conclusion
Upon consideration of the record and for the reasons given, the
rejection of claims 18, 23, 27, 32, 43, and 44 under 35 U.S.C. § 103(a) is
sustained.
Therefore, we affirm the decision of the Examiner.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.
AFFIRMED
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