Ex Parte Forte et al

Patent Trial and Appeal Board

Feb 2, 2018

14007441 (P.T.A.B. Feb. 2, 2018)

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.
14/007,441 10/22/2013 Miguel Forte 0733-1016-1 2158
466 7590 02/06/2018
YOUNG fr THOMPSON
EXAMINER
209 Madison Street JUEDES, AMY E
Suite 500
Alexandria, VA 22314 ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
02/06/2018 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):
DocketingDept@young-thompson.com
y andtpair @ firsttofile. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MIGUEL FORTE and ARNAUD FOUSSAT
Appeal 2017-004576
Application 14/007,441
Technology Center 1600
Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and
RYAN H. FLAX, Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals claims from the
Examiner’s decision to reject claims as anticipated, obvious, and on the
grounds of non-statutory obviousness-type double patenting. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
According to the Specification, regulatory T cells “act to suppress
immune activation and thereby maintain immune homeostasis and tolerance
1 Appellant is the Applicant, TXCELL, which, according to the Brief, is the
real party in interest. Appeal Br. 1.
Appeal 2017-004576
Application 14/007,441
to self-antigens. . . . [There are] natural regulatory T cells (nTreg), type 1
regulatory T cells (Trl) and Th3 cells.” Spec. 1. “The term ‘natural
regulatory T cells’ as used herein refers to cells having the following
phenotype at rest CD4+CD25+FoxP3+.” Id. at 5. “The term ‘Trl cells’ as
used herein refers to cells having the following phenotype at rest
CD4+CD25'FoxP3' and capable of secreting high levels of IL-10 and
intermediate levels of TGF-P upon activation.” Id. “The term ‘Th3 cells’ as
used herein refers to cells having the following phenotype CD4+FoxP3+ and
capable of secreting high levels TGF- [3 upon activation, low amounts of IL-
4 and IL-10 and no IFN-y or IL-2.” Id. at 6.
[0]ne dogma of cell therapy relies on [the belief that the] more
cells to be infused, the better the effect such as seen for
classical pharmaceutical compounds. As infused cells are less
toxic for the patient as a chemical compound may be, great
numbers of cells (108-1010 cells) are generally administrated to
the patients.
Id. at 1. “[T]he surprising observation [by the inventors is] that a low dose
of regulatory T cells is efficient for treating a condition in a subject in need
thereof, whereas the conventional dose for cell therapy is inefficient.” Id. at
3.
Claims 10, 11, 13, 15, and 18 are on appeal, and can be found in the
Claims Appendix2 of the Appeal Brief. Claims 10 and 18 are reproduced
below:
10. A method for treating a human patient having an
inflammatory condition, an autoimmune disease, an allergic or
asthmatic condition, graft-versus-host disease or undergoing a
2 The Claims Appendix indicates that claims 1-9 are canceled and claims 12,
14, 16, 17, and 19-33 are withdrawn from consideration as being directed to
non-elected subject matter. Appeal Br. 18-21.
2
Appeal 2017-004576
Application 14/007,441
transplantation, comprising
administering to the human patient human regulatory
T cells in a therapeutically effective dose of 103 4 to 106 cells,
wherein the inflammatory condition is selected from the
group consisting of inflammatory bowel disease, ulcerative
colitis, Crohn’s disease, intestinal inflammation linked to food
allergy or intolerance, intestinal inflammation linked to milk
protein allergy, intestinal inflammation linked to celiac disease,
intestinal inflammation linked to hen egg allergy, and intestinal
inflammation linked to peanut allergy.
18. The method according to claim 10, wherein the human
patient to be treated is suffering from diabetes, multiple
sclerosis, arthritic condition, inflammatory bowel disease,
ulcerative colitis, Crohn’s disease, or an allergic or asthmatic
condition.
Appeal Br. 18-19, Claims Appendix (formatting and emphasis
added).
Appellant requests review of the following grounds of rejection made
by the Examiner:
I. claims 10, 11, 13, 15, and 18 under 35 U.S.C. § 102(b) as anticipated
or in the alternative under 35 U.S.C. § 103(a) as obvious over
Eshhar;3
II. claims 10, 11, 13, 15, and 18 under 35 U.S.C. § 102(b) as anticipated
or in the alternative under 35 U.S.C. § 103(a) as obvious over
Cheroutre;4
III. claims 10, 11, 13, 15, and 18 under 35 U.S.C. § 102(b) as anticipated
or in the alternative under 35 U.S.C. § 103(a) as obvious over Orban;5
3 Eshhar et al., WO 2008/095141 A2, published Aug. 7, 2008 (“Eshhar”).
4 Cheroutre et al., US 2009/0136470 Al, published May 28, 2009
(“Cheroutre”).
5 Orban et al., US 2009/0142308 Al, published June 4, 2009 (“Orban”).
3
Appeal 2017-004576
Application 14/007,441
IV claims 10, 11, 13, 15, and 18 under 35 U.S.C. § 102(b) as anticipated
or in the alternative under 35 U.S.C. § 103(a) as obvious over
Foussat;6
V claims 10, 11, 13, 15, and 18 are provisionally rejected on the ground
of non-statutory obviousness-type double patenting over claims 9-14
and 20-23 of copending US Application No. 12/682,061 in view of
Orban;
VI. claims 10, 11, 13, 15, and 18 are provisionally rejected on the ground
of non-statutory obviousness-type double patenting over claims 1,5,
7-9, 12, 17, and 20 of copending US Application No. 14/796,284; and
VII. claims 10, 11, 13, 15, and 18 are provisionally rejected on the ground
of non-statutory obviousness-type double patenting over claims 27
and 31^16 of copending US Application No. 13/806,158 in view of
Foussat.7
I. Rejections based on Eshhar
The issue is: Does the preponderance of evidence of record support
the Examiner’s finding that the claims are either anticipated and/or rendered
obvious by Eshhar?
Findings of Fact
FF1. Eshhar teaches a method directed to suppressing undesired activity of
T effector cells by administering redirected Treg cells. Eshhar 19:1-
6 Foussat et al., WO 2009/068575 Al, published June 4, 2009 (“Foussat”).
7 A notice of abandonment issued on Nov. 13, 2017 in US Application
No. 13/806,158 rendering any rejection based on this application moot and
we will not further address this rejection.
4
Appeal 2017-004576
Application 14/007,441
5. The “method is intended for use in situations wherein the T
effector cells mediate an autoimmune inflammatory response or
disorder, rejection of a transplant or GVH disease.” Id. at 19:16-17.
Autoimmune diseases contemplated include “inflammatory bowel
disease (IBD), wherein the antigen or ligand is one that is expressed in
diseased colon or ileum.” Id. at 16:12-13.
FF2. Eshhar teaches applying the Treg cell therapy to human and veterinary
subjects, and teaches that “[t]he preferred subject is a human.” Id. at
43:22-23.
FF3. Eshhar teaches that “[tjypical dosages are between about 106 and
about 1011 Treg cells per injection or infusion, more preferably, about
107 to about 1010 cells.” Id. at 42:23-24.
FF4. Eshhar teaches that “determination of optimal ranges of effective
amounts of a given cell type for a particular disease or condition is
within the skill of the art.” Id. at 42:17-18.
FF5. Specification defines:
The term “treatment” as used herein refers to clinical
intervention in an attempt to alter the natural course of a
disease of the subject to be treated, and may be
performed either for prophylaxis or during the course of
clinical pathology. Desirable effects include, but are not
limited to, preventing occurrence or recurrence of
disease, alleviating symptoms, suppressing, diminishing
or inhibiting any direct or indirect pathological
consequences of the disease, lowering the rate of disease
progression, ameliorating or palliating the disease state,
and causing remission, maintaining remission state or
improving prognosis. Regulatory T cells treatment and
5
Appeal 2017-004576
Application 14/007,441
regulatory T cells therapy are used herein with the same
meaning.
Spec. 3.
Analysis
We have reviewed Appellant’s contention that the Examiner erred in
rejecting claims 10, 11, 13, 15, and 18 as either anticipated and/or obvious
over Eshhar. Appeal Br. 2-6. We are not persuaded by Appellant’s
arguments and generally agree with the Examiner’s findings concerning the
scope and content of the prior art as well as the conclusions set forth in the
Examiner’s Answer and the Final Office Action dated Dec. 14, 2015 (“Final
Act.”). The findings of fact reproduced above are referenced to highlight
certain pertinent evidence. See FF1-FF4. For emphasis, we highlight and
address the following:
Appellant contends that the Examiner’s Answer does not appreciate
the surprising results from the data presented. Reply Br. 3. Specifically,
Appellant contends that the Specification “surprisingly demonstrated (1) the
advantage of the 106 dose regarding CDAI8 score reduction, as well as
IBDQ9 score reduction, and (2) the absence of therapeutic efficacy resulting
from higher doses (as evidenced by the absence of remission at higher
doses).” Reply Br. 3, see also Appeal Br. 4 (“Appellant has demonstrated
that there is no therapeutic effect at a dose greater than 106 cells relative to
treating Crohn’s disease in humans”).
The Examiner finds, and we agree, that “[t]he asserted unexpected
results demonstrating that a dose of 106 ova specific, autologous Trl cells
8 Crohn’s Disease Activity Index (CDAI). Spec. 22.
9 Inflammatory Bowel Disease Questionnaire (IBDQ). Spec. 21.
6
Appeal 2017-004576
Application 14/007,441
administered intravenously was more effective than 107-109 Trl cells in a
specific subset of human patients with Crohn’s disease are not
commensurate in scope with the present claims.” Ans. 8. “[T]he attempt to
demonstrate unexpected results to one claimed subset population is not
commensurate in scope with all of the conditions that are currently claimed.”
Ans. 8. Furthermore, “it is noted that the instant specification does not
demonstrate that doses greater than 106 have no therapeutic effect.” Ans. 7-
8. In other words, claim 10 is not restricted to patients with Crohn’s or
IBD, and Appellant’s have not demonstrated that their results with two
conditions would reasonably predict that other conditions within the scope
of the claims would have the same unexpected result.
Figure 3B of the Specification, reproduced below and relied on by
Appellant, shows the percentage of patients having Crohn’s disease that are
in remission after treatment.
50 ;
10c6 10e7 lOeS 10e9
Doses
“Figure 3B shows the percentage of patients in remission: almost 30% of
patients treated with the dose of 106 cells are in remission, whereas no
patient treated with the higher doses is in remission.” Spec. 22.
The claims, however, are not limited to “remission,” but instead are
generically directed to “treating” a patient population. Thus, again, the
7
Appeal 2017-004576
Application 14/007,441
argument, is not commensurate in scope with the claim. According to the
Specification “treatment” describes a genus of potential outcomes, only one
of which is remission. For example:
Desirable effects include, but are not limited to, preventing
occurrence or recurrence of disease, alleviating symptoms,
suppressing, diminishing or inhibiting any direct or indirect
pathological consequences of the disease, lowering the rate of
disease progression, ameliorating or palliating the disease state,
and causing remission, maintaining remission state or
improving prognosis.
FF5.
As the Examiner points out, Figures 2A and 3 A of the Specification
show that even at higher doses patients with Crohn’s disease respond to
“treatment,” as the term is understood in light of the Specification.
Therefore, Appellant’s arguments with respect to the surprising results of
achieving remission in patients having Crohn’s disease is not persuasive
because these results are not commensurate in scope with the claim. See
Ans. 8.
The Specification’s Figure 3A, reproduced below, shows patients
having Crohn’s disease response to treatment:
y>*4
IX
aw
St
I
eHo©
iS
10e6 10e7 4068 X0e9
Oases
8
Appeal 2017-004576
Application 14/007,441
“Figure 3A[, reproduced above,] shows the percentage of patients that
responded to the treatment in each group: almost all patients responded to
the treatment when treated with the dose of 106 cells, whereas less than 20%
of patients responded to the treatment when treated with the dose of 109
cells.” Spec. 22.
The Specification’s Figure 2A, reproduced below, shows patient
response to treatment:
“Figure 2[A, reproduced above,] shows the cohort responses to the
treatment: the group of patients treated with 106 cells showed a CDAI
decrease of almost 150 points at week 5 and 8, whereas the groups of
patients treated with the higher doses showed a CDAI decrease of less than
50 points (Fig 2A).” Spec. 22.
The Examiner explains that “[w]hile a wide range of cell doses would
be expected to have some therapeutic effect [within the meaning of
“treatment” as explained by the Specification], the level of effectiveness of
Treg treatment will vary based on the condition to be treated, the type of
Treg, the antigen specificity, and the route and frequency of administration.”
Ans. 8. “For example, see Fig 2A demonstrating a CDAI decrease with
higher dosages and Fig 3 A, demonstrating that 107 cells resulted in a
positive response in 70% of the treated patients.” Ans. 8. We agree with the
9
Appeal 2017-004576
Application 14/007,441
Examiner that the results with respect to remission are not commensurate in
scope with the claims.
In so far as Appellant’s argument is directed to “remission” and that
the prior art needs to demonstrate “remission” of a particular disease state,
we note that “remission” is not a limitation found in the claims. It is well
established that limitations not appearing in the claims cannot be relied upon
for patentability. In re Self, 671 F.2d 1344, 1348 (CCPA 1982). We
understand that “treatment,” as described in the Specification, can
encompass “remission,” however, the meaning is not limited to that
interpretation alone. “Treatment” as described in the Specification includes
a genus of effects that also encompass “alleviating symptoms” as well as
“diminishing or inhibiting any direct or indirect pathological consequences
of the disease.” See FF5. Because the term “treatment” is not limited to
remission, as argued by Appellant, we are not persuaded that the reference
does not disclose the limitation as recited in the claims.
With respect to the ground of anticipation based on Eshhar, Appellant
contends that the reference “neither expressly nor inherently teaches a
therapeutically effective dose is 106 for humans as required by independent
claim 10.” Appeal Br. 3. Specifically, Appellant contends that the preferred
dosage in Eshhar is higher than the claimed range, and thereby does not
expressly teach using 106 cells. See Appeal Br. 3 (“preferably, about 107 to
about 1010 cells”).
We are not persuaded by Appellant’s contention that Eshhar does not
disclose a therapeutically effective dose as claimed. Again, Appellant is
arguing a limitation that is not in the claim. In other words, Appellant
contends that Eshhar does not teach remission at treatment doses of using
10
Appeal 2017-004576
Application 14/007,441
106 cells. This argument is not convincing, as pointed about by the
Examiner, because preferred prior art embodiments do not teach away from
the broader prior art disclosure in this case of treating the disease with 106-
1011 cells. Ans. 8, citing In re Susi, 440 F.2d 442 (CCPA 1971); see FFl^l.
Appellant contends that extrapolating the mouse dose of Treg cells
used in Eshhar would lead the ordinary artisan to “concluded that about
3500 fold more cells should be evaluated for administration to a human, i.e.
as 1.75 x 108 human Treg cells or 5.25 x 109 human Treg cells, as possible
therapeutically effective doses.” Appeal Br. 4.
We are not persuaded. “An assertion of what seems to follow from
common experience is just attorney argument and not the kind of factual
evidence that is required to rebut a prima facie case of obviousness.” In re
Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). Appellant is arguing that
because a mouse is so much smaller than a human the dosage is necessarily
adjusted up by a factor 3500 based solely on the difference in size between
the two subjects. Although it may be true that doses administered to a
human may be higher as compared to a mouse, there is no evidence that it is
necessarily based on size alone and other factors may determine the actual
range of Treg cells to administer. In other words, Appellant’s have not
directed us to evidence that animal models directly correlate to in vivo
dosage in humans and that the asserted extrapolation is correct.
Furthermore, preferred embodiments do not teach away from the broader
disclosure in this case treatment in the rage of 106—1011 cells. Ans. 8.
“[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting a prima facie case of unpatentability. If
that burden is met, the burden of coming forward with evidence or argument
11
Appeal 2017-004576
Application 14/007,441
shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
Appellant has not met their burden of showing that the Examiner erred in
rejecting the claims, or otherwise rebutted the Examiner’s cogent response in
the Answer’s “Response to Arguments” (Ans. 5-8) concerning Eshhar.
Accordingly, we affirm the rejection of claim 10 as anticipated and/or
obvious by Eshhar. As claims 11, 13, 15, and 18 have not been argued
separately, they fall together with claim 10. 37 C.F.R. § 41.37(c)(l)(iv).
II. Rejections based on Cheroutre
The issue is: Does the preponderance of evidence of record support
the Examiner’s finding that the claims are either anticipated and/or rendered
obvious by Cheroutre?
Findings of Fact
FF6. Cheroutre teaches that
[rjegulatory T cells, produced in the absence or presence
of an antigen, can be used to provide a subject with
tolerance to an antigen. Thus, a subject that has
developed or is at risk of developing an undesirable or
aberrant immune response against an antigen, such as a
self antigen, can be administered regulatory T cells in
order to provide antigen tolerance to the subject.
Cheroutre ^ 38. Treg cells are known to “maintain immune system
homeostasis and tolerance to self-antigens.” Id. 39.
FF7. Cheroutre teaches that subjects include human subjects. Cheroutre
11 105-7.
FF8. Cheroutre teaches that subjects include those with Crohn’s
disease, inflammatory bowel disease (IBD), graft vs. host
disease (GVIID), among others. See Id. 78, 83, 108-9.
12
Appeal 2017-004576
Application 14/007,441
FF9. Cheroutre teaches that “[f]or a cell based method of treatment, doses
can range from about 100,000 to about 1 billion cells. Exemplary
dose amounts can be an amount of cells ranging from about 500,000
to about 500 million cells, or between about 1-100 million cells, or
between about 1-10 million cells.” Id. ^[135.
FF10. Cheroutre teaches that many factors such as age and severity of
symptom are considered when setting a treatment regime. See Id. ][
130. “Doses can also be empirically, for example, using animal
disease models or optionally in human clinical studies. Initial study
doses can be based upon animal studies, such as primates, and the
amount of compound administered to achieve a prophylactic or
therapeutic effect or benefit.” Id. ][ 133; see also Ans. 9 (“dosing is
within the skill of the art and can readily be determined empirically”).
FF11. Example 8 of Cheroutre, is an animal colitis model that teaches the
animals are
co-transferred with [2.5 x 105] CD4 T cells activated in
the presence of TGF-P were partially protected from
disease, and mice co-transferred with naive T cells and
CD4 T cells activated in vitro in the presence of both
TGF-P and RA [(retinoic acid)], showed no apparent
signs of disease.
Cheroutre]! 197.
Analysis
We have reviewed Appellant’s arguments that the Examiner erred in
rejecting claims 10, 11, 13, 15, and 18 as either anticipated and/or obvious
over Cheroutre. Appeal Br. 6-8. We do not find Appellant’s arguments
persuasive and generally agree with the findings concerning the scope and
content of the prior art as well as the conclusions set forth in the Examiner’s
13
Appeal 2017-004576
Application 14/007,441
Answer and the Final Office Action. The findings of fact reproduced above
are referenced to highlight certain pertinent evidence. See FF6-FF11. For
emphasis, we highlight and address the following:
Appellant contends that “the ordinary artisan would have deduced
from US 2009/0136470 [Cheroutre] that about 8. 75 x 108 human T cells
should be administered to a human patient as the therapeutically effective
amount.” Appeal Br. 7.
We are not persuaded. “An assertion of what seems to follow from
common experience is just attorney argument and not the kind of factual
evidence that is required to rebut a prima facie case of obviousness.” In re
Geisler, 116 F.3d at 1470. Appellant is once more arguing that because a
mouse is so much smaller than a human the dosage is necessarily adjusted
up based solely on the difference in size between the two subjects. Although
it may be true that dose administered to a human may be higher as compared
to a mouse there is no evidence that dosing is necessarily based on size alone
so that it that determines the dose administered to a subject. Cheroutre
teaches that many factors such as age and severity of symptom are
considered when setting a treatment regime. FF10. Cheroutre also teaches
that doses can be determined empirically using primate studies and human
clinical trials. FF10. We note that there is no indication that the dosage
range taught by Cheroutre, namely “from about 100,000 to about 1 billion
cells” is not equally applicable to all subjects, including humans. See FF9
and FF10. Appellant’s argument is based on Cheroutre’s exemplified
treatment in mice (FF11, example 8) and this is not persuasive because
Cheroutre tells us that other factors are also considered when formulating a
treatment protocol. FF10.
14
Appeal 2017-004576
Application 14/007,441
There is insufficient evidence presented that animal models directly
correlate to in vivo dosage in humans. Therefore, the animal models
disclosed in Cheroutre are not necessarily outside the claimed dosage range.
Furthermore, preferred embodiments do not teach away from the broader
disclosure in this case treatment in the range of 100,000 (105) to about 1
billion cells. Ans. 8.
We are also not persuaded by Appellant’s other argument that the
doses disclosed Cheroutre in the range of 100,000 to about 1 billion “are not
expressly taught as being therapeutically effective for treating humans”
Appeal Br. 7. A reference does not have to a carry out the experiments
contemplated in the disclosure in order to anticipate. “[Ajnticipation does
not require actual performance of suggestions in a disclosure. Rather,
anticipation only requires that those suggestions be enabling to one of skill
in the art.” Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d
1368, 1379, (Fed. Cir. 2001) (citing In re Donohue, 766 F.2d 531, 533, (Fed.
Cir. 1985) (“It is not, however, necessary that an invention disclosed in a
publication shall have actually been made in order to satisfy the enablement
requirement.”)).
Cheroutre teaches treating human subjects, such as those that are at
risk of developing an aberrant immune response or those already with the
disease. FF6 and FF7. Disease treatments contemplated include aberrant
immune responses as found in Crohn’s disease or inflammatory bowel
disease (IBD) among others. FF8. Cheroutre also teaches an animal model
for colitis that administers 2.5 x 105 CD4+ cells to the animals and
determines that those cells activate in the presence of TGF-P and retinoic
acid showed no disease. FF11. Thus, the claimed cell dose has been
15
Appeal 2017-004576
Application 14/007,441
determined effective in mice. We are not persuaded by Appellant’s
contention that extrapolating the dosage from a mouse necessarily results in
a concentration of cells that is not effective. It is important to reiterate that
the claimed limitation of “treatment” is not limited to “remission” and can
include alleviating symptoms as well as diminishing or inhibiting any direct
or indirect pathological consequence of disease. See FF5, see also above I.
Appellant has not met their burden of showing that the Examiner
erred in rejecting claims, or otherwise rebutted the Examiner’s cogent
response in the Answer’s “Response to Arguments” (Ans. 6-9) concerning
Cheroutre. Accordingly, we affirm the rejection of claim 10 as anticipated
and/or obvious by Cheroutre. As claims 11, 13, 15, and 18 have not been
argued separately, they fall together with claim 10.
III. Rejections based on Orban
The issue is: Does the preponderance of evidence of record support
the Examiner’s finding that the claims are either anticipated and/or rendered
obvious by Orban?
Findings of Fact
FF12. Orban teaches that cell therapy methods are useful for treating
autoimmune diseases (see 33^42), including type 1 diabetes
mellitus (T1DM) in a human subject. See Orban ^ 60-63. The
methods generate “regulatory T cells [that] can be isolated from a
subject, expanded in vitro, and re-introduced into either the same or a
different subject.” Id. 51.
FF13. Orban teaches that the dose of regulatory T cells can be determined by
a clinician. See id. ^ 57.
16
Appeal 2017-004576
Application 14/007,441
Generally, the dose begins with an amount somewhat less than
the optimum dose and it is increased by small increments
thereafter until the desired or optimum effect is achieved
relative to any negative side effects. For example, populations
of cells comprising at least about 104, 105, 106, 10s, 109, 1010, or
more purified and expanded regulatory T cells as described
herein can be administered, e.g., in one or more doses.
Id. T| 57.
Analysis
We have reviewed Appellant’s arguments that the Examiner erred in
rejecting claims 10, 11, 13, 15, and 18 as either anticipated and/or obvious
over Orban. Appeal Br. 9-11. We do not find Appellant’s arguments
persuasive and generally agree the findings concerning the scope and
content of the prior art as well as the conclusions set forth in the Examiner’s
Answer and the Final Office Action. The findings of fact reproduced above
are referenced to highlight certain pertinent evidence. See FF12-FF13. For
emphasis, we highlight and address the following:
Appellant contends that, at best, Orban “describes how to determine a
therapeutically effective dose, without specifying any therapeutically
effective doses for treating humans.” Appeal Br. 10. And, further,
“[ijndeed, there are no exemplified therapeutically effective doses for
treating humans.” Id.
We are not persuaded by Appellant’s argument that the art has to have
exemplified the treatment in order to find the reference anticipatory. Orban
teaches the production of regulatory T cells as well as reinfusing these cells
into a patient. FF12. Orban describes that the clinician can determine the
proper dose and provides the guideline to start at a low dose and gradually
17
Appeal 2017-004576
Application 14/007,441
increasing the dose to balance therapeutic effect versus negative side effect.
FF13. The lowest starting dose contemplate in Orban is 104 cells and goes
up to 1010 cells. FF13. Because the disclosed range encompasses the
claimed range of cells administered to a patient, we agree with the
Examiner’s finding that the range is anticipated by Orban. Orban teaches
the application of the method to treat autoimmune disease such as diabetes
mellitus. FF12. Orban thereby adequately describes how to go about
obtaining the regulatory T cells from a patient, expanding these cells, and
how to use the cells for treating patients with autoimmune disease such as
diabetes mellitus. FF12-13. An actual working example is not required to
establish anticipation because all the steps of the claimed method are
expressly described by Orban. A reference does not have to perform the
suggestion provided in the disclosure. Bristol-Myers Squibb, 246 F.3d at
1379. Consequently, we agree with the Examiner’s finding that Orban
anticipates the claims.
Insofar as Appellant’s argument is directed to unexpected results with
respect to remission, we are also unpersuaded. See Appeal Br. 10-11. As
discussed above (see I. and II.) because the claims are not limited to
remission, we agree with the Examiner that Appellant has not met their
burden of demonstrating unexpected results because reliance on “ova-
specific Trl regulatory T cells in Crohn’s disease [is] not commensurate in
scope with the present claims.” Ans. 10.
Appellant has not met its burden of showing that the Examiner erred
in rejecting claims, or otherwise rebutted the Examiner’s cogent response in
the Answer’s “Response to Arguments” (Ans. 9-10) concerning Orban.
Accordingly, we affirm the rejection of claim 10 as anticipated and/or under
18
Appeal 2017-004576
Application 14/007,441
35 U.S.C. § 103(a) as unpatentable by Orban. As claims 11, 13, 15, and 18
have not been argued separately, they fall together with claim 10.
IV. Rejections based on Foussat
The issue is: Does the preponderance of evidence of record support
the Examiner’s finding that the claims are either anticipated and/or rendered
obvious by Foussat?
Findings of Fact
FF14. Foussat teaches a method for “treating intestinal inflammation linked
to food allergy or intolerance” for example milk protein allergy,
peanut allergy, and ovalbumin allergy. Foussat 6:23-27.
FF 15. Foussat teaches administering autologous human Trl cells autologous
to the subject. See id. at 6:29-30. “[Hjuman Trl cells autologous to
the cells of said subject. This means that Trl cells will be
administrated to the subject they come from.” Id. at 20:6-9.
FF16. Foussat teaches a range of cells for administration. Specifically,
“104/kg to 109/kg cells are administrated to the subject. Preferably
105/kg to 107/kg cells and more preferably about 106/kg cells are
administrated to the subject.” Id. at 19:21-23.
FF17. The Examiner finds that a dose of 104 cells/ kg “would correspond to
a dose of 7 x 105 cells for an average weight human subject of 70kg,
which would fall within the claimed range.” Ans. 4.
Analysis
We have reviewed Appellant’s arguments that the Examiner erred in
rejecting claims 10, 11, 13, 15, and 18 as either anticipated and/or obvious
19
Appeal 2017-004576
Application 14/007,441
over Foussat. Appeal Br. 11-13. We do not find Appellant’s arguments
persuasive and generally agree with the findings concerning the scope and
content of the prior art as well as the conclusions set forth in the Examiner’s
Answer and the Final Office Action. The findings of fact reproduced above
are referenced to highlight certain pertinent evidence. See FF14-FF17. For
emphasis, we highlight and address the following:
Appellant acknowledges that Foussat teaches that “104/kg to 109/kg
cells are administered to the subject,” but does not teach a therapeutically
effective amount. Appeal Br. 12. Appellant contends that the experimental
data would indicate that “the administration of about 109 human cells to a
human patient (i.e. a mouse typically weights about 20 g, while a human
typically weights about 70 kg)” and the teachings are thereby not
anticipatory. Appeal Br. 12.
We are not persuaded. As acknowledged by the Examiner the
teachings of a reference “is not limited only to the preferred embodiments or
the specific examples.” Ans. 10. As such, Foussat teaches treating intestinal
inflammation caused by a food allergy by administering autologous Trl
cells. FF14-15. The reference provides that cells should be administered at
a concentration range of 104/kg to 109/kg cells. FF16. The Examiner finds
that the lowest dose would be equivalent to 7 x 105 cells in an average 70 kg
subject. FF17. This is well within the range claimed. Foussat instructs to
administer a dosage of autologous cells at concentration of 104/kg cells to a
subject suffering from intestinal inflammation. FF14-15. Here, the
references teaches one of ordinary skill to administer the same cells to the
same patient population, using the same product in this case autologous Trl
20
Appeal 2017-004576
Application 14/007,441
cells to treat the same condition, therefore, the therapeutic effect would be
expected to be the same. We find no error with the Examiner’s finding.
Appellant contends that the Specification demonstrates “in the
Examples that the T cell doses greater than 106 cells are not therapeutically
effective.” Appeal Br. 10; see Reply Br. 3.
We are not persuaded by Appellant’s contentions for the reason set
out by the Examiner in the Answer and for those discussed above (see I.-III).
To reiterate the claims are not limited to achieving a treatment endpoint that
is limited to remission, but instead encompasses a much larger genus of
endpoints. Accordingly, we agree with the Examiner that the claims are not
commensurate in scope with the unexpected results.
Appellant has not met their burden of showing that the Examiner
erred in rejecting the claims, or otherwise rebutted the Examiner’s cogent
response in the Answer’s “Response to Arguments” (Ans. 10-11)
concerning Foussat. Accordingly, we affirm the rejection of claim 10 as
anticipated and/or obvious by Foussat. As claims 11, 13, 15, and 18 have
not been argued separately, they fall together with claim 10.
V. Obviousness-Type Double-Patenting Over US Application
No. 12/682,061 in view of Orban
The issue is: Does the preponderance of evidence of record support
the Examiner’s conclusion that the claims are unpatentable over the claims
in the copending US Application No. 12/682,061?
Findings of Fact
FF18. Claim 910 of US Application No. 12/682,061 recites:
10 Claims submitted in the cited application by After Final Amendment of
21
Appeal 2017-004576
Application 14/007,441
9. (Currently Amended) A method for treating an
autoimmune disease, an inflammatory disease or an
allergic disease in a subject, comprising administering to
said subject an effective amount of a medicament
comprising Trl cells and mesenchymal stem cells (MSC),
wherein said MSC are autologous,
and
wherein the MSC and Trl cells are administered
simultaneously, or the MSC are administered first and
then the Trl cells are administered 24 to 48 2& hours after
MSC administration.
FF19. Claim 11 of US Application No. 12/682,061 depends on claim 9,
above, and further recites that the autoimmune disease is selected
from the group including Crohn’s disease.
Analysis
Appellant contends that the copending application does not disclose
administering an effective amount of medicament in the range claimed. See
Appeal Br. 13-14. According to Appellant Orban does not remedy this
missing element because the reference exemplifies in Example 8 a dose that
exceeds the currently claimed range. See Appeal Br. 14.
We are not persuaded because the unexpected results relied upon by
Appellant that forms the basis of their argument are not commensurate in
scope with the claims. See above III (discussing Orban and unexpected
results). Accordingly, we affirm this rejection for the reasons set out by the
Examiner. Ans. 11-12.
May 26, 2016, entered by the Examiner with the Advisory Action of July 1,
2016.
22
Appeal 2017-004576
Application 14/007,441
VI. Obviousness-Type Double-Patenting Copending US Application
No. 14/796,284.
Appellant contends that the provisional double patenting rejection
should be withdrawn “when the application with the earliest U.S. effective
filing date issues as a patent.” See Appeal Br. 15, citing MPEP 804 I. B. 2.
The Examiner acknowledges this procedural requirement in the Answer and
indicates that the “obviousness type double patenting rejections will be
withdrawn when they are the only rejection remaining.” See Am,. 12. As
Appellant provides no other substantive arguments with respect to this
rejection, we affirm the rejection for the reasons given by the Examiner as
set out in the Final Action and Answer. See Final Act. 9; see Ans. 12.
SUMMARY
We affirm the rejection based on Eshhar.
We affirm the rejection based on Cheroutre.
We affirm the rejection based on Orban.
We affirm the rejection based on Foussat.
We affirm the rejection of claims 10, 11, 13, 15, and 18 on the ground
of non-statutory obviousness-type double patenting over copending US
Application No. 12/682,061.
We affirm the rejection of claims 10, 11, 13, 15, and 18 on the ground
of non-statutory obviousness-type double patenting over copending US
Application No. 14/796,284.
23
Appeal 2017-004576
Application 14/007,441
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
24