Ex Parte Imran

Patent Trials and Appeals Board

Mar 25, 2019

14152647 - (D) (P.T.A.B. Mar. 25, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/152,647 01/10/2014
119282 7590 03/27/2019
Alston & Bird LLP/ InCube Labs, LLC
Bank of America Plaza
101 South Tryon Street, Suite 4000
Charlotte, NC 28280-4000
FIRST NAMED INVENTOR
Mir Imran
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.
059883-441342 1074
EXAMINER
CANELLA, KAREN A
ART UNIT PAPER NUMBER
1643
NOTIFICATION DATE DELIVERY MODE
03/27/2019 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):
usptomail@alston.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MIR IMRAN
Appeal2018-006048
Application 14/152,647
Technology Center 1600
Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134(a) involving claims to a
method of using stem cell-derived cancer cells to measure an immune
response. The Examiner rejected the claims as failing to comply with the
enablement requirement. 3 We have jurisdiction under 35 U.S.C. § 6(b). We
affirm.
1 Appellant identifies the Real Party in Interest as Incube Labs Inc. (see App.
Br. 2).
2 We have considered and herein refer to the Specification of Jan. 10, 2014
("Spec."); Final Office Action of Oct. 20, 2016 ("Final Act."); Appeal Brief
of Jan. 12, 2018 ("App. Br."); and the Examiner's Answer of Feb. 23, 2018
("Ans.").
3 The Examiner withdrew a written description rejection of claims 1, 3-9,
14, 15, 23-25, and 31 in the Advisory Action of Jan. 8, 2018.
Appeal2018-006048
Application 14/152,647
Statement of the Case
Background
"[M]any discoveries have been made in understanding stem cells.
There have been proposals to use stem cells for treating a wide variety of
afflictions, including Parkinson's disease, spinal cord injuries, amyotrophic
lateral sclerosis, and multiple sclerosis" (Spec. 1 ). "Described herein are
novel methods for the use of stem cells for the treatment of cancer" (id.).
The Claims
Claims 1, 3-9, 14, 15, 23-25, and 31 are on appeal. 4 Independent
claim 1 is representative and reads as follows:
1. A method for measuring an immune response in a cancer
patient, the method comprising:
providing stem cell-derived cancer cells (SCDCCs), the
SCDCCs having been produced by culturing cancer cells
removed from the patient in the presence of stem cells under
conditions such that the stem cells differentiate into SCDCCs
and wherein differentiation of the stem cells into the SCDCCs
is indicated by monitoring differentiation of the stem cells and
identifying the disappearance of one or more stem cell markers
and/ or by identifying the appearance of one or more
tumorigenic antigens on the stem cells, wherein the
disappearance of the one or more stem cell markers and/ or the
appearance of the one or more tumorigenic antigens indicates
that the stem cells have differentiated into SCDCCs;
introducing an amount of the SCDCCs into the patient;
and
measuring a characteristic of the patient's cancer,
wherein the characteristic includes at least one or more of tumor
4 Appellant cancelled claims 2, 10-13, 16-22, 26-30, and 32--44 in the
Amendment after Final of Nov. 20, 2017.
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Application 14/152,647
size, titer of cancer cells in the patient, and rate of cancer cell
proliferation in the patient, wherein a decrease in at least one of
these characteristics is indicative of an immune response in the
patient.
The Issue
The Examiner rejected claims 1, 3-9, 14, 15, 23-25, and 31 under
35 U.S.C. § 112(pre-AIA), first paragraph, for failing to comply with the
enablement requirement (Ans. 3-7).
The Examiner finds:
The specification provides no evidence that the co-
culture of cancer cells with stem cells can result in stem-cell
derived cancer cells (SCDCC) that provide an immunogenic
target in a patient with cancer which can overcome tolerance to
the patient's own tumor cells .... There is no expectation that
the stem cells which have acquired some unknown
characteristic of the tumor cells, or have lost some characteristic
of the starting stem cells can be an efficient immunogen in a
cancer patient such that tolerance to the patient's cancer cells
can be overcome and that an antibody which inhibits or
destroys the patient's cancer cells can be evoked
(Ans. 3).
Appellant contends:
The specification provides examples of responses of a
human patient to the introduction of SCDCCs such as "inducing
the patient's immune system to produce antibodies which
inhibit or destroy the patient's cancer cells," "reductions in one
or more of tumor size, titer of cancer cells in the patient's body,
rates of cancer cell proliferation in the patient's body and rates
and/or activity levels of various metastatic processes in the
patient's body" (see, e.g., page 7, lines 7-21)
(App. Br. 3--4).
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Application 14/152,647
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner's conclusion that the
Specification does not enable the claimed invention.
Findings of Fact ("FF'')
Breadth of the Claims
1. Claim 1 broadly encompasses a method for measuring an
immune response in a cancer patient by: providing stem cell-derived cancer
cells (SCDCCs ), introducing SCDCCs into the patient, and measuring a
characteristic of the patient's cancer indicative of an immune response in the
patient.
2. Claim 1 broadly encompasses any type of stem cell as
evidenced by dependent claims. Claims 4 and 5 demonstrate that the range
of stem cells extends from embryonic and fetal stem cells to hematopoietic
stem cells. Claim 3 recognizes the further breadth includes any genetically
modified stem cell. Claims 6-8 recognize even further breadth, including
pluripotent stem cells that can give rise to any cell type in a body,
multipotent cells that are more limited and can only develop into certain cell
types, and oligopotent stem cells that are even more limited and develop into
only a few cell types.
3. Claim 1 broadly encompasses any stem cell or tumorigenic
antigen marker on cells.
4. Claim 1 broadly encompasses any cancer, with the
Specification stating
Embodiments of such methods are generally applicable to the
treatment of any kind of cancer, including adenocarcinoma,
leukemia, lymphoma, melanoma, myeloma, sarcoma,
teratocarcinoma, and cancers of the adrenal gland, bladder,
bone, bone marrow, brain, breast, cervix, gall bladder, ganglia,
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Application 14/152,647
gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary,
pancreas, parathyroid, penis, prostate, salivary glands, skin,
spleen, testis, thymus, thyroid, and uterus.
(Spec. 2-3).
Presence of Working Examples
5. Appellant contends "[t]he specification provides examples of
responses of a human patient to the introduction of SCDCCs ... " (App. Br.
3--4, citing Spec. 7 :7-21) but these examples are not a working example.
6. The Specification provides prophetic discussions of general
possible responses of a human patient to the introduction of SCDCCs (see
Spec. 3:7-21; 7:4--11).
7. The Specification provides no working examples (see Spec. 1-
8).
Amount of Direction or Guidance Presented
8. The Specification states "[t]he stem cells used can include
embryonic, fetal, and adult stem cells" (Spec. 2: 16-29).
9. The Specification states "[ e ]mbodiments of such methods are
generally applicable to the treatment of any kind of cancer" (id.)
10. The Specification states "[a]n amount of the SCDCC is then
introduced into the patient sufficient to induce the patient's immune system
to produce antibodies which inhibit or destroy the patient's cancer cells"
(Spec. 2: 11-13).
11. The Specification describes the step of: "introducing an
amount of the SCDCC into the patient sufficient to evoke an allograft
rejection response, such as inducing the patient's immune system to produce
antibodies which inhibit or destroy the patient's cancer cells" (Spec. 3: 11-
13 ).
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12. The Specification states "[t]he production of such antibodies
along with other aspects of the allograft rejection response provide for
reductions in one or more of tumor size, titer of cancer cells in the patient's
body, [and] rates of cancer cell proliferation in the patient's body" (Spec. 3:
13-17).
13. The Specification states "the type and number of SC DCC
introduced into the patient can be titrated for obtaining one or both of a
specific reduction in the titer of cancer cells or the rate of proliferation of
cancer cells" (Spec. 3: 19-21 ).
Relative Skill in the Art
14. The Examiner finds "the skill in the art is high" (Ans. 4).
State of the Prior Art and Unpredictability of the Art
15. Ferrand5 teaches (mesenchymal stem cells) "MSC have been
reported to give rise to other cell types including epithelial cells. However,
due to the lack of good in vitro models, mechanisms of MSC epithelial
differentiation and wound repair remain poorly understood and the few data
available are controversial" (Ferrand 1, col. 2).
16. Ferrand teaches "the presence of MSC in the tumoral
environment could [] favor cancer development by differentiation into
tumor-associated fibroblasts contributing to angiogenesis and metastasis
formation, although this role remains controversial" (Ferrand 2, col. 1 ).
5 Ferrand et al., Human Bone Marrow-Derived Stem Cells Acquire Epithelial
Characteristics through Fusion with Gastrointestinal Epithelial Cells, 6
PLoS One 1-11 (2011).
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1 7. Ferrand teaches "we demonstrated for the first time that MSC
can acquire epithelial characteristics through a fusion mechanism with
gastric and intestinal epithelial cells" (Ferrand 5, col. 2).
18. Ferrand teaches the fusion process "involves a loss of
mesenchymal markers expression" and is "confirmed by the protein
expression of two specific epithelial markers not expressed by MSC alone"
(id.).
19. Ferrand teaches "the model of direct co culture ... could be
considered to be closer in a way to the physiological context compared to
indirect coculture using previously described cell culture insert systems,
where trans-differentiation events were observed. In our study, cell culture
inserts did not allow trans-differentiation events" (id.).
20. Ferrand teaches "MSC fusion with gastrointestinal epithelial
cells may involve a reprogramming of the fused cells rendering them more
susceptible to transformation and leading to the appearance of cancer stem
cells .... Alternatively, MSC fusion with epithelial cells could promote the
cancerous process rather than initiate it" (Ferrand 7, col. 1).
Quantity of Experimentation
21. The Specification teaches "one or more aspects of the methods
of the invention can be adjusted to achieve particular reductions in one or
more of [ the patient's cancer characteristics] measurements" (Spec. 3: 17-
18).
22. The Specification states:
Experiments can be performed using various
immunological methods known in the art to enhance and/or
optimize the number of cancer cell antigens (such as a cancer
cell surface antigen) that are incorporated into the SCDNICC's
[sic]. These results in tum can be used to enhance and/ or
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Application 14/152,647
optimize the patient's immune response to the cancer cells so as
to kill or otherwise inhibit the patient's cancer cells
(Spec. 5:19-23).
Principles of Law
When rejecting a claim under the enablement requirement of
section 112, the PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of
protection provided by that claim is not adequately enabled by
the description of the invention provided in the specification of
the application.
In re Wright, 999 F.2d 1557, 1561---62 (Fed. Cir. 1993).
Factors to be considered in determining whether a disclosure
would require undue experimentation ... include ( 1) the
quantity of experimentation necessary, (2) the amount of
direction or guidance presented, (3) the presence or absence of
working examples, ( 4) the nature of the invention, ( 5) the state
of the prior art, ( 6) the relative skill of those in the art, (7) the
predictability or unpredictability of the art, and (8) the breadth
of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
Analysis
In addressing the Wands factors, we find that the balance of the
evidence supports the Examiner's position that the scope of protection is not
adequately enabled by the description of the invention provided by the
Specification. Because a patent specification must enable the full scope of a
claimed invention, we begin our enablement inquiry with a construction of
the claims. See Chiron v. Genentech, 363 F.3d 1247, 1254 (Fed. Cir. 2004).
Appellant argues "the Examiner bases the rejection in part on
language and limitations not found in the pending claims" (App. Br. 5).
Appellant argues "current claim 1 does not recite 'sufficient to induce the
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patient's immune system to produce antibodies which inhibit or destroy the
patient's cancer cells,'" in contrast to the Examiner's statements (id., citing
Final Act. 3).
While we agree with Appellant that claim 1 does not require SCDCCs
sufficient to induce the production of antibodies, this interpretation results in
a claim that is unduly broad because the broadest reasonable interpretation
of the claim encompasses any change in tumor size, cancer cell titer or rate
of cancer cell proliferation in any cell in any cancer as "indicative of an
immune response" (FF 2, 4). In contrast, Appellant provides no working
example of any such change in a single cell type or a single type of cancer
(FF 5-7), nor does Appellant provide detailed guidance demonstrating that
such changes necessarily occur, that the changes are predictable, or allowing
the ordinary artisan to predictably perform the method over the immense
scope of cancers and cell types encompassed by claim 1 (FF 1--4, 8-13).
Appellant contends the "Examiner has not met the PTO' s burden of
showing undue experimentation" because "the quantity of experimentation
necessary to make the SCDCCs of the claims and to measure an immune
response is not great and in any event involves no more than routine
repetition of the same procedure described in the specification" (App. Br. 4).
While the Examiner does not dispute enablement for providing
SCDCCs and measuring an immune response (see Ans. 4 ), the Examiner
determines that there is no predictable basis that an immune response will be
evoked in the patient by introducing an amount of SCDCCs into the patient
based on the disclosure and the state of the art (see Ans. 4--5). Moreover,
the Examiner finds there "is no objective evidence to conclude that the
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phenotype of the SDCCs [sic] would remain the same after injection" (Ans.
5).
We agree with the Examiner, as Appellant focuses on the methods for
preparing the SCDCCs, and does not address the step of introducing an
amount of SCDCCs into a cancer patient. The Specification provides no
working examples of SCDCCs in any amount to be introduced into a cancer
patient (FF 5-7). The Specification further provides no working examples
in the form of experimental data, either in vitro or in vivo, to establish what
type or number of SCDCCs would generate an immune response (id.).
Rather, the examples cited by Appellant are all generic recitations of
introducing SCDCCs with invitations to perform future experiments (see FF
21-22). Due to the wide variety of stem cells, cancer cells, and potential
immune responses generated by introducing SCDCCs into a cancer patient,
the amount of experimentation needed to practice the full scope of the
claims is vast.
The Examiner acknowledges that the level of skill in the art is high,
however, finds that the state of the art is unpredictable (Ans. 5). In contrast,
Appellant argues "[t]he state of the art is advanced in that the claimed
SCDCCs can be made by standard methodology" (App. Br. 4). Appellant
cites Ferrand, published after the claimed priority date of the application (as
a continuation of application No. 12/800,925, filed May 24, 2010), to
establish co-culturing stem cells with a variety of cell types, including
cancer cells, leads to cell fusion and differentiation (see App. Br. 6).
We are not persuaded by Appellant's argument. We find that the
claims are not limited to the specific stem cells taught by Ferrand, i.e., bone
marrow derived cells (BMDC) and MSC. Moreover, the claims are not
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Application 14/152,647
limited to the fusion products taught by Ferrand. Rather than establish a
known technology with a standard methodology, we find that Ferrand
teaches the art was unpredictable near the time of the filing the application.
See In re Goodman, 11 F.3d 1046, 1051 (Fed. Cir. 1993) ("the references
cited by [Appellant] to show enablement support the Board's position that
great uncertainties encumbered [the technology]"). For example, we find
Ferrand teaches the mechanisms of MSC epithelial differentiation were
poorly understood due to a lack of good in vitro models (FF 15, 16, 20). We
find Ferrand, published after the filing date of the application, demonstrated
for the first time that MSC acquired epithelial characteristics by cell fusion
(FF 17). Moreover, we find Ferrand teaches that the role of MSC in the
tumoral environment remains "controversial" and proposes two different
roles for MSC fusion with epithelial cells in the cancer process for further
exploration (FF 15, 16). See Goodman, 11 F.3d at 1050 ("article expressly
invited further 'investigation' to determine whether the method works").
Thus, even in the limited MSC model of Ferrand, there was significant
unpredictability. The claims are not limited to MSCs, to epithelial cancers,
or to any specific markers found on the stem cells. In summary, we find
Ferrand supports the Examiner's position that creating SCDCCs, much less
introducing SCDCCs into a cancer patient, was an unpredictable and nascent
technology.
We think this situation is similar to In re '318, where our reviewing
court found that "[t]hus, at the end of the day, the specification, even read in
the light of the knowledge of those skilled in the art, does no more than state
a hypothesis and propose testing to determine the accuracy of that
hypothesis. That is not sufficient." In re '318 Patent Infringement
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Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009). See also Rasmusson v.
SmithKline Beecham Corp., 413 F.3d 1318, 1325 (Fed. Cir. 2005) ("mere
plausibility ... is not consistent with the statutory requirement that the
inventor enable an invention rather than merely proposing an unproved
hypothesis").
Conclusion of Law
A preponderance of the evidence of record supports the Examiner's
conclusion that the Specification does not enable the claimed invention.
SUMMARY
In summary, we affirm the rejection of claims 1, 3-9, 14, 15, 23-25,
and 31 under 35 U.S.C. § 112, first paragraph for failing to comply with the
enablement requirement.
No time period for taking any subsequent action in connection with
this appeal may be extended under 3 7 C.F .R. § 1.13 6( a).
AFFIRMED
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