Ex Parte Foussat et al

Patent Trial and Appeal Board

Mar 14, 2018

12989857 (P.T.A.B. Mar. 14, 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.
12/989,857 10/27/2010 Arnaud Foussat 0733-1014 3408
466 7590 03/16/2018
YOUNG fr THOMPSON
EXAMINER
209 Madison Street GOUGH, TIFFANY MAUREEN
Suite 500
Alexandria, VA 22314 ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
03/16/2018 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ARNAUD FOUSSAT, VALERIE BRUN,
HELENE ASNAGLI, NATHALIE BELMONTE, and
CHRISTIAN JORGENSEN
Appeal 2017-004656
Application 12/989,857
Technology Center 1600
Before ULRIKE W. JENKS, JOHN E. SCHNEIDER, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellants1 appeal from the
Examiner’s decision to reject claims directed to a pharmaceutical
composition comprising Trl cells. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify TXCELL as the real party in interest. Appeal Br. 1.
Appeal 2017-004656
Application 12/989,857
STATEMENT OF THE CASE
Although a wide range of drugs are available, a
successful treatment for inflammatory arthritis is still a major
unmet medical need. While biologic DMARDs [(disease
modifying anti-rheumatic drugs)] are offering the most
promising route to slowing or even halting this disease, they
work only for a proportion of patients: even for the most
effective anti-TNF therapy, at least one third of RA
[(Rheumatoid Arthritis)] patients do not respond.
Spec. 4:17-21.
Claims 1, 2, 4, 5, and 26—29 are on appeal, and can be found in the
Claims Appendix of the Appeal Brief. Claim 1 is representative of the
claims on appeal, and reads as follows:
1. A pharmaceutical composition consisting essentially of at
least one human Trl cell population directed against a joint-
associated antigen and one or more pharmaceutically acceptable
carriers, wherein said joint-associated antigen is elected from
the group consisting of collagen type II peptides, human
cartilage glycoprotein 39 (HCgp 39) peptides and fragments,
variants and mixtures thereof.
Appeal Br. 14 (Claims Appendix).
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Application 12/989,857
The claims stand rejected as follows:
I. Claims 1, 2, 4, 5, and 26—29 are rejected under 35 U.S.C. § 103(a) as
unpatentable over Foussat,2 Groux ’97,3 Groux ’663,4 Groux ’406,5 in
view of Londei,6 Sekine,7 and Kotzin.8
II. Claims 1, 2, 4, 5, and 26—29 are provisionally rejected under the
nonstatutory obviousness-type double patenting.
III. Claims 1, 2, 4, 5, and 26—29 are rejected under 35 U.S.C. § 101 as
being directed to a judicial exception.
I Obviousness
The issue is: Does the preponderance of evidence of record support
the Examiner’s conclusion that the combination of references renders the
composition comprising Trl cells directed against a joint-associated antigen
obvious?
2 Foussat et al., Corporative Study between T -Regulatory Type 1 and
CD4+CD25+ T Cells in the Control of Inflammation, 171 Journal of
Immunology 5018-26 (2003) (“Foussat”).
3 Groux et al., A CD4+T-cell subset inhibits antigen-specific T-cell
responses and prevents colitis, 389 Nature 737-42 (1997) (“Groux ’97”).
4 Groux et al., US 2008/0107663 Al, publ. May 8, 2008 (“Groux ’663”).
5 Groux et al., WO 2007/010406 A2, publ. Jan. 25, 2007 (“Groux ’406”).
6 Londei et al., Persistence of collagen type Il-specific T-cell clones in the
synovial membrane of a patient with rheumatoid arthritis, 86 PNAS 636-40
(1989) (“Londei”).
7 Sekine et al., Type II collagen is a target antigen of clonally expanded T
cells in the synovium of patients with rheumatoid arthritis. 58 Ann Rheum
Dis. 446-50 (1999) (“Sekine”).
8 Kotzin et al., Use of soluble peptide-DR4 tetramers to detect synovial T
cells specific for cartilage antigens in patients with rheumatoid arthritis. 97
no. 1 PNAS 291-96 (2000) (“Kotzin”).
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Application 12/989,857
Findings of Fact
We agree with the Examiner’s factual findings as set out in the
Answer and Office Action dated Sept. 9, 2015. We highlight the following
for emphasis only:
FF1. Foussat teaches that “repetitive Ag-specific stimulation of CD4+ T
cells in the presence of IF-10 lead to the generation of another
population of Tr cells (Trl) predominantly producing IF-10.”
Foussat 5018.
FF2. Foussat teaches that “treatment of mice with Trl cells and OVA
[(ovalbumin)] administration was followed by a remission of all
inflammatory signs in the colon” in a mouse model of chronic
inflammatory bowel disease (IBD). Foussat 5023.
FF3. Groux ’97 teaches that “Trl cells can also be generated from human
peripheral blood. Both alloantigen-specific CD4+ T-cell clones
(JDV24) and non-alloantigen-specific T-cell clones (JDV15, JDV308
and JDV94) displaying the Trl cell cytokine profile were derived
from CD4+ T cell populations that had initially been stimulated with
allogeneic monocytes in the presence of IF-10. Groux ’97, 737—738.
FF4. Groux ’97 teaches that in an inflammatory bowel disease (IBD)
mouse model the “transfer in SCID mice of as few as 2 X 105 OVA-
specific Trl cells . . . prevents IBD induced by pathogenic CD4+
CD45RBhl splenic T cells. Not surprisingly, the Trl cells are effective
only upon stimulation in vivo by feeding the mice with OVA.”
Groux ’97, 740.
FF5. Groux ’663 teaches activating a Trl cell population in vitro and then
administering the antigen activated Trl cell population to a subject.
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Application 12/989,857
Groux ’663 12—14. “[T]he method includes administering from 106
to 109 antigen-activated Trl cells/kg, for example from 0.5 107 to 1.5
107 cells/kg, preferably 107 cells/kg.” Groux ’663 116, see id. 1 53.
FF6. Groux ’406 teaches that Trl cells can be used to treat inflammatory
diseases. See Groux ’406, 1:19-27.
FF7. Groux ’406 discloses a method of stimulating peripheral blood
mononuclear cell (PBMC) or leukocyte population with a food- or
auto-antigen and recovering the stimulated cells. See Groux ’406
2:25-3:2. “‘[A]uto-antigen’ refers to an immunogenic peptide derived
from a protein of said individual,” and lists numerous possible
antigens. See Groux ’406, 4:12—5:9.
FF8. The Examiner acknowledges that neither Foussat, Groux ’97,
Groux ’663, nor Groux ’406 “teach Trl cells directed to a joint-
associated antigen.” Ans. 5.
FF9. Londei teaches that in rheumatoid arthritis (RA) T cells are
responsible “in maintaining the chronic inflammatory state in
rheumatoid arthritis, since there is abundant HLA class II and
collagen type II available to restimulate the T cells.” Londei 636.
Londei teaches that “almost any joint constituent could be the relevant
autoantigen(s)” for stimulating T cells. Londei 637.
FF10. Sekine teaches that type II collagen (CII) “recognising T cell clones
were among those accumulated T cells in the synovium. Our results
strongly suggested that CII is recognised by the clonally expanded T
cells in the synovium of RA patients.” Sekei 449. “Our findings
suggest that expansion of oligoclonal T cells in the RA joints is driven
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Application 12/989,857
at least in part by intra-articular autoantigens, such as CII.” Sekine
450.
FF11. Kotzin teaches that “type II collagen (CII) and human cartilage gp39
(HCgp39) are among the most likely synovial antigens to be involved
in T cell stimulation in RA.” Kotzin, Abstract.
Principle of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Analysis
Appellants contend that “the prior art documents teach locally
administering OVA to the inflammation site in combination with OVA-
specific Trl cells. . . . The skilled artisan would never have deduced from
this disclosure that an auto-antigen naturally present on the inflammation
site may be sufficient to activate Trl cells in vivo.” Reply Br. 3^4; see also
Appeal Br. 10 (“the proposed modification would render the Trl cells by
FOUSSAT, GROUX ’97, GROUX ’633 and WO ’406 unsatisfactory for
their intended purpose and their identified advantages (i.e., when the antigen
to which the Trl cells are directed is independent from the pathology)”).
Foussat, Groux ’97, Groux ’663, and Groux ’406 teach that the
production of IL-10 at the site of inflammation helps alleviate symptoms of
inflammation. See FF1—FF7. The references teach a method of in vitro
stimulating Trl cells and re-stimulating these Trl cells in vivo in order to
allow for a vigorous response from the cells in an in vivo setting. See FF2,
FF4, FF6. Re-stimulation of the Trl cells requires the presence of antigen.
See FF2 and FF4. The Examiner acknowledges that neither Foussat, Groux
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’97, Groux ’663, nor Groux ’406 “teach Trl cells directed to a joint-
associated antigen.” FF8.
Londei, Sekine, and Kotzin teach that type II collagen (CII) and
human cartilage gp39 (HCgp39) are antigens present in synovial fluid of
patients suffering from rheumatoid arthritis. See FF9—FF11.
Applying the KSR standard of obviousness to the findings of fact, we
agree with the Examiner that it would have been obvious to an ordinary
artisan to substitute a joint-associated antigen for the ovalbumin antigen or
auto-antigen in the production of Trl cells knowing that there is “a clear
correlation between collagen type II and its role as an autoantigen in the
inflammatory disease RA. . . . Trl antigen-directed cells when re-stimulated
with the antigen in vivo are known for treating diseases associated with the
antigen or autoantigens, in this case collagen 11 in RA patients.” Ans. 7.
There would have been a reasonable expectation of success “because the
composition would be [re-]activated by the presence of the autoantigen in
the patient.” Ans. 7.
It is obvious to those skilled in the art to substitute one known
equivalent for another. See In re Omeprazole Patent Litigation, 483 F.3d
1364, 1374 (Fed. Cir. 2007) (“[Tjhis court finds no . . . error in [the]
conclusion that it would have been obvious to one skilled in the art to
substitute one ARC [alkaline reactive compound] for another.”); see In re
Fout, 675 F.2d 291, 301 (CCPA 1982) (“Express suggestion to substitute
one equivalent for another need not be present to render such substitution
obvious.”). We find no error with the Examiner’s position that the
substitution of one known auto-antigen (FF7) for another auto-antigen (FF9—
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FF1) would have been obvious for the production of Trl cells in vitro in
order to arrive a composition comprising such Trl cells.
Appellants contend that there is no expectation “that an auto-antigen
naturally present on the inflammation site may be sufficient to activate Trl
cells in vivo.” See Reply Br. 4. We are not persuaded by Appellants’
position that the Examiner’s combination lacks a reasonable expectation of
success. Kubin stated that, “[Responding to concerns about uncertainty in
the prior art influencing the purported success of the claimed combination,
this court [in O ’Farrell] stated: ‘ [ojbviousness does not require absolute
predictability of success ... all that is required is a reasonable expectation of
success.’” In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re
O’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988)).
The factors produced by the Trl cells are effective to treat
inflammation regardless of the cause of the inflammation; but in order to
produce these factors, the Trl cells must see the antigen that is used to create
them. FF1—FF7. The Examiner relies on other references to show that the
synovial fluid of RA patients contains certain antigens. FF9—FF11. The
presence of these antigens in the diseased joints makes these antigens an
ideal target for directing therapeutics. These references teach that the T cell
population responsible for causing the inflammation in the joint are
continuously re-stimulated to maintain the inflammation in the joint. See
FF9—FF11. The teaching that there is sufficient antigen in the joint to cause
one type of T cell to proliferate and expand provides reasonable expectation
that the amount of antigen present in the joint would be sufficient to also
stimulate Trl cells because these cells are also T cells. See Ans. 8. There is
no evidence that Trl cells require more antigen for the purpose of re-
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Application 12/989,857
stimulation of the cells than is required for the maintenance (re-stimulation)
of an inflammatory T cell. FF9. Therefore, we agree with the Examiner’s
conclusion that
one of ordinary skill in the art knowing that collagen II is a
well-known joint autoantigen present in the synovium of
rheumatoid arthritis (RA) patients and that RA is characterized
by T-cell infiltration of the joints would have been motivated to
make a composition consisting essentially of at least one Trl
cell directed against a joint antigen, specifically collagen II
intended for administration to a patient suffering from an
inflammatory disease given the teachings of the prior art of
record. Trl antigen-directed cells when re-stimulated with the
antigen in vivo are known for treating diseases associated with
the antigen or autoantigens, in this case collagen II in RA
patients.
Ans. 8. Appellants have not persuasively explained why the combination of
references does not teach the claimed limitation, or why the substitution of a
different auto-antigen to produce Trl cells for the purpose of creating a
composition is not a “predictable use of prior art elements according to their
established functions” and therefore obvious. KSR, 550 U.S. at 417.
Appellants’ argument that “[t]he skilled artisan would never have
deduced from this disclosure that an auto-antigen naturally present on the
inflammation site may be sufficient to activate Trl cells in vivo” constitutes
no more than a conclusory argument without supporting evidence, and is
unpersuasive. Reply Br. 4. “Attorney’s argument in a brief cannot take the
place of evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974).
We affirm the rejection of claim 1. Claims 2, 4, 5, 26, and 27 were
not argued separately and fall with claim 1. 37 C.F.R. § 41.37 (c)(l)(iv).
Appellants present the same arguments with respect to claims 28 and 29.
We are not persuaded for the same reasons discussed above for claim 1.
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II. Provisional Nonstatutory Obviousness-Type Double Patenting
The issue is: Does the evidence of record support the Examiner’s
conclusion that the claims of the co-pending application read on the claims
of the present application?
Findings of Fact
FF12. Claim 19 of copending U.S. Patent Application No. 14/007,441,
submitted June 14, 2016, reads as follows:
19. (withdrawn) A composition comprising a
therapeutically effective dose of 104 to 106 human
regulatory T cells.
Analysis
Appellants contend that none of the claims of the co-pending
application “refers to Trl cells directed against joint associated antigens
selected from collagen type II peptides. . . . Consequently, at best, the
claims of ’441 [co-pending application] refer to a genus, whereas the instant
claims correspond to a species.” Appeal Br. 3.
We find that Appellants have the better position. “[A] one-way’ test
has been applied to determine obviousness-type double patenting. Under
that test, the examiner asks whether the application claims are obvious over
the patent claims.” In re Berg, 140 F.3d 1428, 1432 (1998). In Berg the,
application claims were directed to a genus while the patent contained a
species. See Id. at 1430. Under this scenario the Federal Circuit found the
obviousness-type double patenting rejection proper. The facts before us in
the present appeal, however, are the opposite of those presented in Berg
thereby leading to the opposite conclusion.
Here, the Examiner finds “that the instant claims are a species of the
generic genus of human regulatory T cells claimed in ’441 [co-pending
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application].” Ans. 3. A genus may render a species obvious provided there
is some reason to direct the ordinary artisan to select the particular species
out of the much larger genus. On the facts before us in this appeal, we find
that the Examiner has not explained why the selection of the presently
claimed species from the disclosed genus in the co-pending application
would have been obvious. Accordingly, we reverse this provisional
nonstatutory obviousness-type double patenting rejection.
III. Nonstatutory Subject Matter
The Examiner finds that “[cjlaim 1 is directed to a nature-based
product, which is not markedly different from its naturally occurring
counterpart. . . found in the peripheral blood of RA patients.” Final Act. 3.
Appellants do not present arguments with respect to this rejection. See
Appeal Br. 2—3. We thus summarily affirm the rejection.
SUMMARY
We affirm the rejection of claims 1, 2, 4, 5, and 26—29 under 35
U.S.C. § 103(a) as obvious.
We reverse the provisional rejection of claims 1, 2, 4, 5, and 26—29
under the nonstatutory obviousness-type double patenting.
We summarily affirm the rejection of claims 1, 2, 4, 5, and 26—29
under 35 U.S.C. § 101.
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
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