Ex Parte Ho et al

Patent Trial and Appeal Board

Aug 23, 2018

11797322 (P.T.A.B. Aug. 23, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
11/797,322 05/02/2007
56719 7590 08/27/2018
MEDLER FERRO WOODHOUSE & MILLS PLLC
8201 Greensboro Drive, Suite 1060
McLean, VA 22102
TonyW. Ho
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.
0154-0002US4 6355
EXAMINER
KIM, TAEYOON
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
08/27/2018 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):
docketing@medlerferro.com
tmedler@medlerferro.com
aferro@medlerferro.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TONY W. HO, GENE C. KOPEN, WILLIAM F. RIGHTER,
J. LYNN RUTKOWSKI, and JOSEPH WAGNER 1
Appeal2016-007472 2
Application 11/797 ,322
Technology Center 1600
Before TONI R. SCHEINER, ULRIKE W. JENKS, and
ELIZABETH A. LA VIER, Administrative Patent Judges.
SCHEINER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the final rejection of
claims directed to an isolated cell population of human bone marrow-derived
cells. The claims stand rejected under the doctrine of obviousness-type
double patenting, and under 35 U.S.C. § 101 as directed to patent-ineligible
subject matter. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm the double patenting rejection, and reverse the rejection
under§ 101.
1 Appellants identify the Real Party in Interest as Gamet BioTherapeutics,
Inc. Appeal Br. 3.
2 An oral hearing was held on May 2, 2018.
Appeal2016-007472
Application 11/797 ,322
BACKGROUND
The Specification discloses a substantially homogeneous human cell
population which co-expresses CD49c, CD90 and telomerase, but not CD34
or CD45. Spec. 11. Briefly, a "Primary Cell Bank" was generated by
aspirating bone marrow cells from the iliac crest of healthy adult human
volunteers; recovering a mononuclear cell fraction from the aspirate; seeding
the mononuclear cell suspension in a tissue culture flask at a density of
50,000 cells/cm2, and incubating for 5 days at 37QC in an atmosphere
consisting of 5% carbon dioxide, 5% oxygen, and 90% nitrogen/air;
recovering adherent colony forming units (CPUs) and expanding the CPUs
for an additional 3-5 days; and recovering and re-suspending adherent cells
and freezing them for storage. More than 91 % of the adherent population
was CD90 and CD49c positive. Id. at 21-24.
A "Master Cell Bank" was generated by culturing an aliquot of cells
from the Primary Cell Bank at a density of 30 cells/cm2 for two weeks at
37QC in an atmosphere consisting of 5% carbon dioxide, 5% oxygen, and
90% nitrogen/air. Id. "The purity of the cells (percentage of cells which co-
express CD49c/CD90) in the Master Cell Bank was determined" and it was
found to contain "a substantially homogenous population of adherent cells
which co-express CD49c and CD90 and lack significant expression of the
[myeloid-related] marker CD45." Id. at 24.
In addition, the doubling rate of the cells from the Master Cell Bank
"was 30 hrs and remained constant for at least 50 doublings." Id. at 25.
"Even after 30 doublings, the population uniformly retained the
characteristic morphology of small, dividing cells without apparent evidence
2
Appeal2016-007472
Application 11/797 ,322
of the enlarged, flat morphology of aged or terminally-differentiated cells."
Id.
Finally, the Specification teaches that "most human cells lack
telomerase, [thus] telomeres shorten with each division until the cells growth
arrest." Id. at 26. According to the Specification, however, "[c]ell
populations which co-express CD49c and CD90 express telomerase at the
level of approximately 13 transcripts/106 transcripts of 18S rRNA, which is
consistent with the finding that this cell population continued to proliferate
at a constant rate." Id. at 27.
STATEMENT OF THE CASE
Independent claim 133 and dependent claims 136-138 are on appeal.
Claims 134 and 135, the only other claims pending, have been withdrawn
from consideration. Appeal Br. 4. Claim 133 is representative and reads as
follows:
133. An isolated cell population of human bone marrow-
derived cells, wherein said cell population has been cultured in
vitro at cell seeding densities of about 30 cells/cm2 under about
5% oxygen conditions for more than 30 population doublings,
wherein said cell population continues to maintain a population
doubling time of about 30 hours per doubling and wherein
greater than 91 % of the cells in said cell population continue to
co-express cell surface markers CD49c and CD90, and wherein
said cell population does not express cell surface markers CD34
or CD45, and wherein said cell population expresses telomerase
at a relative expression of between about 1 transcript of
telomerase per 106 transcripts of an 18s rRNA and about 10
transcripts of telomerase per 106 transcripts of an 18s rRNA.
Claims 133 and 136-138 stand rejected under the doctrine of
obviousness-type double patenting, and under 35 U.S.C. § 101 as directed to
patent patent-ineligible subject matter.
3
Appeal2016-007472
Application 11/797 ,322
DOUBLE PATENTING
The Examiner provisionally rejected claims 133 and 136-138 on the
ground of nonstatutory obviousness-type double patenting as unpatentable
over claims 14, 21, 25, 26, and 97 of U.S. Application No. 09/960,244 (now
US Patent No. 9,969,980), and claims 1-11, 57---60, and 63 of U.S.
Application No. 10/251,685 (now US Patent No. 9,969,977).
The patented claims, like the present claims, are directed to an
isolated cell population derived from human bone marrow cells wherein
greater than 91 % of the cell population co-expresses CD49c and CD90, and
the cell population maintains a doubling rate of less than 30 hours after 30
cell doublings. Appellants have not addressed this rejection on the merits.
See Appeal Br. 19. Accordingly, the rejection of claims 133 and 136-138
on the ground of obviousness-type double patenting is summarily affirmed.
STATUTORY SUBJECT MATTER
Claims 133 and 136-138 stand rejected under 35 U.S.C. § 101 as
directed to patent-ineligible subject matter, specifically, a "product of
nature" without "markedly different characteristics from what occurs in
nature." Ans. 2, 3.
Appellants contend that the Examiner's initial burden of establishing a
prima facie case of lack of subject matter eligibility has not been met
(Appeal Br. 6), and even if the Examiner's initial burden has been met,
Appellants have provided evidence sufficient to rebut a prima facie case (id.
at 10). The evidence relied on by Appellants includes the Declaration of Dr.
Vanessa Ragaglia (signed October 29, 2014 ("Ragaglia Deel.")), explaining
why "the claimed cell population is not a natural product, and is markedly
different from what is found in nature" (Appeal Br. 10), as well as a number
4
Appeal2016-007472
Application 11/797 ,322
of references purporting to show that "culture conditions greatly affect the
phenotype, i.e., structure, and behavior of a cell" (id. at 11 ). Dr. Ragaglia
states that she is an expert in the field of "stem cells and cell biology, and
mesenchymal stem cells in particular" (Ragaglia Deel. ,r 1 ), and provides
evidence of this expertise (id., Appendix A).
Principles of Law
35 U.S.C. § 101 states that"[ w ]hoever invents or discovers any new
useful process, machine, manufacture, or composition of matter, or any new
and useful improvement thereof, may obtain a patent therefor, subject to the
conditions and requirements of this title."
"Laws of nature, natural phenomena, and abstract ideas are not
patentable." Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S.
Ct. 1289, 1293 (2012) (citation omitted). The Supreme Court articulated a
two-step test for patent eligibility under § 101 that "distinguish[ es] patents
that claim laws of nature, natural phenomena, and abstract ideas from those
that claim patent-eligible applications of those concepts." Alice Corp. Pty.
Ltd. v. CLS Bank Int'!, 134 S.Ct. 2347, 2355 (2014) (citing Mayo, 132 S.Ct.
at 1296-97). "First," Alice instructs us to "determine whether the claims at
issue are directed to one of those patent-ineligible concepts." Id. (citation
and quotations omitted). If the claims are directed to a patent ineligible
concept then the court must proceed to the second step of the test-the
"search for an inventive concept-i.e., an element or combination of
elements that is sufficient to ensure that the patent in practice amounts to
significantly more than a patent upon the ineligible concept itself." Id.
( quotations and alterations omitted).
5
Appeal2016-007472
Application 11/797 ,322
When the invention is alleged to be a product of nature (i.e., a natural
phenomenon), the patent-eligibility inquiry concerns whether the product is
"new 'with markedly different characteristics'" than anything found in
nature. Ass 'nfor Molecular Pathology v. Myriad Genetics, Inc., 569 U.S.
576, 577, 590 (2013).
Issue
The issue raised by this rejection is whether the Examiner has
established that the claimed cell population is patent ineligible because it is
not markedly different from a progenitor cell population that exists in vivo.
Findings of Fact (FF)
The following findings of fact are pertinent to the issue raised by this
appeal:
FPL Javazon3 teaches that "ease of expansion in culture is one of the
primary advantages of MSCs [mesenchymal stem cells], [but] it also may
alter their fundamental nature." Javazon, 421, col. 1. "The cumulative data
support a model of culture expansion altering the in vivo biology of the
MSC in ways that may be detrimental to some clinical applications but
perhaps are beneficial to others." Id.
FF2. Zhang4 teaches that MSCs-a subpopulation of bone marrow
derived stromal cells with the ability to differentiate into multiple cell
types-are known to spontaneously differentiate and lose multipotency after
3 Elizabeth H. Javazon et al., Mesenchymal stem cells: Paradoxes of
passaging, 32 EXPERIMENTAL HEMATOLOGY 414-425 (2004) ("Javazon")
( submitted by Appellants).
4 Douglas Zhang & Kristopher A. Kilian, The effect of mesenchymal stem
cell shape on the maintenance of multipotency, 34 BIOMATERIALS 3962-
3969 (2013) ("Zhang") (submitted by Appellants).
6
Appeal2016-007472
Application 11/797 ,322
prolonged passaging ex vivo. Zhang, 3962, col. 2. However, Zhang teaches
that certain cell culture conditions affect nmltipotency----e.g., confining
MSCs to small islands on a patterned substrate, rather than a non-patterned
substrate, enhances expression of mesenchymal stem cell markers and
preserves the ability of the cells to differentiate into adipocytes and
osteoblasts, even after the cells are released from the islands and reseeded.
Id. at 3963, col. 1.
FF3. Kiefer5 teaches that "supplements within a medium can greatly
influence cellular phenotypes." Kiefer, Abstract. For example, Kiefer
demonstrates that "cells cultured in BGM [basic cell growth medium] had
efficient population doublings ... and retained ASC [adipose stem cell]
markers CD44 and CD90, but had poor capacity to differentiate." Id. at 35.
In contrast, KNAC [keratinocyte N acetyl-L-cysteine supplemented
medium] and MAPC [ multipotent adult progenitor cell medium] cultured
cells had longer doubling times but retained the capacity to differentiate into
multiple lineages." Id.
FF4. Bain6 teaches "[a]fter short-term expansion of MSCs from p3 to
p5, chemotactic migration capacity decreased, whereas cell attachment rate
increased." Bain, 163. In addition, "[c]ell functional characteristics ... are
5 Kristina M. Kiefer et al., The Influence of Culture Medium Type on
Cellular Phenotype of Canine Adipose Derived Stem Cells, 3 OPEN JOURNAL
OF REGENERATIVE MEDICINE 28-37 (2014) ("Kiefer") (submitted by
Appellants).
6 Owen Bain et al., Altered hMSC functional characteristics in short-term
culture and when placed in low oxygen environments: implications for cell
retention at physiologic sites, 9 REGEN. MED. 153-165 (2014) ("Bain")
( submitted by Appellants).
7
Appeal2016-007472
Application 11/797 ,322
altered during short-term expansion and when moved from normoxic
conditions typical of the bioprocess environment to reduced oxygen levels
that reflect human injury sites." Id.
Discussion
The Examiner finds that the claimed cell population is "obtained from
a naturally occurring human body," and "[t]here is no indication in the
specification that the isolated cells have been modified by applicants or the
claimed cells have any characteristics ( structural, functional or otherwise)
that are markedly different from naturally occurring counterparts." Ans. 3.
The Examiner acknowledges that "the claimed culture condition changes
[the] phenotypes of the claimed cells," but contends that "[s]uch adjustment
to their environment is due to the cells' innate or inherent property." Id. at
8. In the Examiner's view, "appellant's culturing procedure is not intended
to produce the claimed cells with the claimed properties, rather appellant
merely discovered the characteristics/properties of the cells after culturing
the isolated cells under the claimed condition[ s]," thus, "the claimed
feature[s] of the cells are independent from any effort of appellant." Id. at 6.
Appellants contend that the Examiner has not identified a naturally
occurring counterpart of the claimed cells; nor has the Examiner "provided
any references showing that a cell population exists in vivo having the
features of the claimed cell population." Appeal Br. 10. Moreover,
Appellants note that claim 133's "culturing step recites that the cell
population has been cultured in vitro at cell seeding densities of about 3 0
cells/cm2 under about 5% oxygen conditions for more than 30 population
doublings," but contend that "[t]he Examiner has not established that the
culturing aspect[s] of the claims are routine or conventional." Id. at 9.
8
Appeal2016-007472
Application 11/797 ,322
Appellants contend that the "characteristics of the claimed cells are the
direct result of the inventor's experimentation with low oxygen and low
density culture conditions." Reply Br. 4. Finally, Appellants have provided
evidence purporting to establish that "[ c ]ulture conditions alter cell
characteristics, such as phenotype (i.e., structure) and function" (Ragaglia
Deel. ,r 6), and "the Office is incorrect in concluding that the cell population
of claim 133 is a natural product that is not significantly different from a
naturally occurring product" (id. ,r 5).
In support of her position, Dr. Ragaglia cites multiple reports showing
"the profound influence of culture conditions on the [MSC's] phenotype and
behavior, and [that] once a cell is removed from its native environment, its
phenotype and behavior are subject to change." Ragaglia Deel. ,r 17. For
example, Dr. Ragaglia cites Javazon as teaching that discrepancies in the
phenotypes of isolated and cultured MS Cs arise due in part to differences in
isolation and culture conditions (id. ,r 11 ); Zhang as teaching that "MS Cs
cultured without confinement have higher levels of osteogenic markers" (id.
,r 18); Kiefer as teaching that different culture media have different effects
on cellular phenotype, doubling time, cytokine production, and ability to
differentiate into stromal lineages (id. ,r 19); and Bain as teaching that even
very brief culture can alter the attachment and chemotactic behavior of
MSCs (id. ,r 10). See FFs 1--4. Finally, Dr. Ragaglia acknowledges that "an
MSC is different and distinct from the cell population recited in claim 133"
(id. ,r 7), but asserts that "[t]he conclusions regarding the structural
differences between in vivo and in vitro MSCs can be extrapolated to the
claimed cell population" (id. ,r 9).
9
Appeal2016-007472
Application 11/797 ,322
The Examiner dismissed the evidence discussed by Dr. Ragaglia-
without addressing Dr. Ragaglia's assertion that differences between in vivo
and in vitro MSCs can be extrapolated to the claimed cell population-
because Appellants "did not establish that MSCs in vivo are [the] naturally
occurring counterpart of the claimed cells, [thus] the feature of MSCs
discussed cannot be considered as the characteristics of the naturally
occurring counterpart of the claimed cells." Ans. 9.
In our view, as with utility rejections under § 101, the Examiner has
the initial burden of establishing that the claimed subject matter falls under a
judicial exception to patent eligibility. See In re Swartz, 232 F.3d 862, 864
(Fed. Cir. 2000) (utility under 35 U.S.C. § 101). Assuming, for the purpose
of deciding this appeal, that the Examiner's initial burden has been met, "the
burden shifts to applicant to submit evidence sufficient to convince" one of
ordinary skill in the art (id.) that the claimed subject matter is not directed to
a judicial exception, i.e., a product of nature. Again, the relevant inquiry in
this appeal is whether the claimed cell population is "new 'with markedly
different characteristics"' from anything found in nature. Myriad, 569 U.S.
at 590. As discussed above, Appellants provided rebuttal evidence in the
form of "multiple reports ... show[ing] the profound influence of culture
conditions on [a] cell's phenotype and behavior, and [that] once a cell is
removed from its native environment, its phenotype and behavior are subject
to change." Ragaglia Deel. ,r 17. The Examiner acknowledged that "the
claimed culture condition changes [the] phenotypes of the claimed cells"
(Ans. 8), but nevertheless maintained that "the claimed invention does not
have markedly different characteristics from what occurs in nature" (id. at
3). The Examiner has not persuasively identified any inadequacy in
10
Appeal2016-007472
Application 11/797 ,322
Appellants' rebuttal evidence, nor has the Examiner provided scientific
reasoning or evidence sufficient to support a finding that the claimed
isolated cell population is a product of nature, lacking markedly different
characteristics from a naturally occurring counterpart.
Accordingly, we reverse the rejection of claims 133 and 136-138
under 35 U.S.C. § 101.
SUMMARY
The rejection of claims 133 and 136-138 under the doctrine of non-
statutory obviousness-type double patenting is AFFIRMED.
The rejection of claims 133 and 136-138 under 35 U.S.C. § 101 is
REVERSED.
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
11