Ex Parte Mallat et al

Patent Trials and Appeals Board

May 9, 2019

13790771 - (D) (P.T.A.B. May. 9, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/790,771 03/08/2013
30743 7590 05/10/2019
W&CIP
11491 SUNSET HILLS ROAD
SUITE 340
RESTON, VA 20190
FIRST NAMED INVENTOR
Ziad Mallat
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.
l l 450029USB 8920
EXAMINER
KOLKER, DANIELE
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
05/10/2019 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Exparte ZIAD MALLAT, HAFID AIT-OUFELLA,
ALAIN TEDGUI, and THOMAS TEDDER
Appeal2017-011503
Application 13/790,771
Technology Center 1600
Before DEBORAH KATZ, JOHN G. NEW, and DAVID COTTA,
Administrative Patent Judges.
KATZ, Administrative Patent Judge.
DECISION ON APPEAL
Appeal2017-011503
Application 13/790,771
Appellants 1 seek our review, under 35 U.S.C. § 134(a), of the
Examiner's decision to reject claims 8 and 12, Appellants' only pending
claims. (Appeal Brief filed March 27, 2017 ("App. Br.") 1.) We have
jurisdiction under 35 U.S.C. § 6(b). An oral argument was held on
May 2, 2019. We AFFIRM.
Appellants claim a method of treating the specified subjects diagnosed
with an ischemic disorder with anti-human CD20 antibody to deplete or
destroy mature B cells or to interfere with their function. (See Specification
("Spec.") 3:13-21.)
Appellants' claim 8, modified with the addition of spacing and
indentations, recites:
A method for increasing fractional shortening in a subject
diagnosed with an ischemic disorder with myocardial necrosis
characterized by a myocardial infarction, comprising the step of
administering a sufficient quantity of an anti-human
CD20 antibody to said subject,
wherein said anti-human CD20 antibody depletes or
destroys mature B cells or interferes with B cell functions in
said subject and increases fractional shortening, and
wherein no other agent is administered with said anti-
human CD20 antibody,
wherein said myocardial infarction is an ST segment
elevation myocardial infarction.
(App. Br. 20, Claims App'x.) Appellants explain that fractional shortening
is a measure of the pump function of the heart and is indicative of decreased
1 Appellants report that the real parties in interest are Institut National de la
Sante et de la Recherche Medicale (INS ERM) of Paris, France and Duke
University of Durham, North Carolina. (App. Br. 3.)
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myocardial wall thickness due to a mycocardial infarction. (See App. Br.
12.)
The subjects recited in claim 8 are those "diagnosed with an ischemic
disorder with myocardial necrosis characterized by a myocardial infarction."
(Id.) Claim 8 further defines the type of myocardial infarction as being "an
ST segment elevation myocardial infarction."2 (See App. Br. 20.)
Appellants explain in their Appeal Brief that
[t]he present inventors were the first to demonstrate that B cell
depletion is effective as a treatment, e.g., when administered
within a few hours of onset of myocardial infarction, that the
claimed treatment is effective after myocardial infarction
independently of atherosclerosis, and that the treatment depletes
or interferes with B cells while increasing fractional shortening.
(App. Br. 5 (emphasis added).) Despite this explanation, Appellants'
claimed methods do not include any limitation on the time after the onset of
the myocardial infarction when the anti-CD20 antibody is administered.
The Examiner rejected claims 8 and 12 under 35 U.S.C. § I03(a) over
U.S. patent application publication 2008/0095771 Al, published April 24,
2008 ("Barron") and U.S. patent application 2010/0093636 Al, published
April 15, 2010 ("Schultz"). (See Final Office Action, issued December 20,
2016 ("Final Act.") 2--4.) Appellants did not argue for the separate
2 Appellants do not provide a definition of "ST segment elevation
myocardial infarction," but we understand this claim term to refer to a type
of myocardial infarction characterized by a specific electrocardiogram trace.
Appellants do not raise any issue of the specific characteristics of this type
of myocardial infarction in their briefs.
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patentability of the rejected claims. Accordingly, we focus on claim 8 in our
review.
Findings of Fact
1. Barron teaches a method of depleting B cells in a patient having
an autoimmune disease by administering to the patient only an antibody that
binds human CD20 or an antigen binding fragment thereof. (See Barron
,r,r 12 and 17 .)
2. Barron teaches that an autoimmune disease of the described
method includes "thrombocytopenia 3 ( as developed by myocardial infarction
patients, for example) .... " (Barron ,r 29.)
3. Appellants' Specification discloses that one hour after mice
having a myocardial ischemic injury are treated by intraperitoneal injection
of a mouse monoclonal CD20 antibody, fractional shortening increased,
suggesting that the treatment may be beneficial for the treatment of
myocardial infarction. (See Spec. 23, Example 2.)
4. Shultz teaches modulating a disorder of the cardiovascular
system by administering a first active agent, which both inhibits
inflammation and treats a cardiovascular disorder, a second anti-
inflammatory agent, and an agent that only treats the cardiovascular
disorder. (See Shultz ,r 24.)
5. Shultz teaches that a second anti-inflammatory agent can be the
anti-CD20 antibody, rituximab. (See Shultz ,r 78.)
3 We understand thrombocytopenia to be a condition of low platelets. (See
App. Br. 21, Evidence Appendix, Mayo Clinic, "Diseases and Conditions:
Thrombocytopenia (low platelet count).")
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6. Shultz teaches that the cardiovascular disorder treated can be
ST segment elevation in myocardial infarction. (See Shultz ,r 79.)
Analysis
We agree with the Examiner's finding that Barron teaches treatment
of myocardial infarction with full length anti-human CD20 antibody, which
depletes B-cells. (See Answer issued August 4, 2017 ('Ans.") 2.) Although
Barron refers to thrombocytopenia, it refers to "thrombocytopenia ( as
developed by myocardial infarction patients, for example)" (Barron ,r 29),
which we understand to mean thrombocytopenia that develops in patients as
a result of a myocardial infarction. We also agree with the Examiner's
finding that Barron teaches administering full length anti-CD20 antibody to
patients without another agent. (See id.)
The Examiner finds that anti-CD20 antibody will inherently increase
fractional shortening when administered to a patient having had a
myocardial infarction. (See Ans. 2, citing Spec. 23.) We agree that
Example 2 of Appellants' Specification supports this finding. (See FF 3.)
Although Barron does not teach that the myocardial infarction at issue
is an ST segment elevation myocardial infarction, the Examiner cites Shultz
for its teaching that a specific anti-CD20 antibody (rituximab) can be used as
a second anti-inflammatory agent, along with other anti-inflammatory agents
that target the RANTES/PF4 interaction and a cardiovascular agent, in
treatment for ST segment elevation myocardial infarction. (See Ans. 2; see
Shultz ,r,r 24, 78, 79,288,289, and claims 21, 22, and 24.)
According to the Examiner, Appellants' claimed method would have
been prima facie obvious to one of ordinary skill in the art at the time
because Barron teaches treating myocardial infarction with full length anti-
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human CD20 antibody and Schultz teaches treating cardiovascular disease,
such as ST segment elevation myocardial infarction, with drugs including
rituximab. (Ans. 3.) The Examiner notes that even though Schultz teaches
treatment of ST segment elevation myocardial infarction with rituximab in
combination with another agent, Barron teaches treating myocardial
infarction per se, encompassing ST segment elevation myocardial infarction
and other forms, with full length anti-human CD20 antibody alone. (Ans.
3.) We agree with the Examiner.
Appellants argue that Barron is focused on treating autoimmune
diseases, mentioning myocardial infarction only once. (See App. Br. 11 and
14; see also id. at 17 and Reply Brief filed September 13, 2017 ("Reply
Br.") 1-2.) We are not persuaded by Appellants' arguments that Barron and
Shultz mention myocardial infarction only in a long "laundry list" of
diseases because our reviewing court has "reject[ ed] the notion that one of
these ingredients cannot anticipate because it appears without special
emphasis in a longer list. To the contrary, the disclosure is prior art to the
extent of its enabling disclosure." Perricone v. Medicis Pharm. Corp., 432
F.3d 1368, 1376 (Fed. Cir. 2005); see Merck & Co. v. Biocraft Laboratories,
Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) ("That the '813 patent discloses a
multitude of effective combinations does not render any particular
formulation less obvious."); see also Beckman Instr., Inc. v. LKB Produkter
AB, 892 F.2d 1547, 1551 (Fed. Cir. 1989) ("[e]ven if a reference discloses
an inoperative device, it is prior art for all that it teaches.").
We are also not persuaded by Appellants' argument that Barron does
not teach treating myocardial infarction itself, but instead teaches treating
only thrombocytopenia, which may or may not develop into myocardial
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infarction. (See App. Br. 11.) On its face, Barron teaches using anti-CD20
antibody to treat "thrombocytopenia ( as developed by myocardial infarction
patients) .... " (Barron ,r 29.) Thus, we agree with the Examiner that
Barron teaches treating patients with myocardial infarction patients. (See
Ans. 2.)
Even though Barron teaches treating a related, resulting condition,
thrombocytopenia, it still teaches treating myocardial infarction patients.
(See Ans. 4 ("There is no limitation in the claims under consideration
regarding the treated disease other than that said disease is myocardial
infarction of the kind as per recited in the claims." ( emphasis omitted).)
Appellants' claimed methods do not recite any limitations on when the
method is used after myocardial infarction. (See id.) Appellants do not
argue or direct us to any definition in the Specification of "subject diagnosed
with an ischemic disorder with myocardial necrosis characterized by a
myocardial infarction" or of "ST segment elevation myocardial infarction"
that limits the claimed subjects to a population being treated at any particular
time in relation to the myocardial infarction. Appellants have also not
directed us to any information about whether an ordinarily skilled artisan
would attempt to increase fractional shortening in the claimed subjects
within hours, days, months or years of the myocardial infarction. Thus,
under the broadest reasonable interpretation, we interpret Appellants'
claimed method to encompass treating myocardial infarction patients after
they have developed conditions such as thrombocytopenia that result from
the infarction. See In re ICON Health & Fitness, Inc., 496 F.3d 1374, 1379
(Fed. Cir. 2007) ("[T]he PTO must give claims their broadest reasonable
construction consistent with the specification .... Therefore, we look to the
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specification to see if it provides a definition for claim terms, but otherwise
apply a broad interpretation.").
Although we agree with Appellants that Barron does not specifically
teach treating ST segment elevation myocardial (see App. Br. 11 ), this
argument does not persuade us that Appellants' claimed method is
patentable because the Examiner's rejection is that the method is obvious
over the combination of the teachings of Barron and Shultz. Shultz teaches
including anti-CD20 antibody in treatments of ST segment elevation
myocardial infarction and Barron teaches treating myocardial infarction
patients, in general, with anti-CD20 antibody. An obviousness analysis
"need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ." KSR
Int'! Co. v. Teleflex Inc., 550 U.S. 398,418 (2007). We agree with the
Examiner that the teachings to use anti-CD20 antibody in patients diagnosed
with myocardial infarction would have rendered Appellants' claimed
methods obvious.
Appellants' arguments against the Examiner's reliance on Shultz are
also unpersuasive because the Examiner does not cite Shultz as teaching to
use anti-CD20 antibody to treat cardiovascular disease alone. (See App. Br.
16; see Reply Br. 3--4.) Instead, the Examiner cited Shultz to show that one
of ordinary skill in the art would have included anti-CD20 antibody to treat
patients with the specific type of myocardial infarction claimed along with
other drugs. (See Ans. 2-3.) The Examiner cites Barron for its teaching of
administering only anti-CD20 antibody to treat myocardial infarction
patients.
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Appellants argue further that none of the cited prior art teaches that
autoimmune diseases, the focus of Barron, are associated with decreased
fractional shortening. (See App. Br. 12.) This argument does not persuade
us of the patentability of Appellants' claims because Example 2 of
Appellants' Specification indicates that fractional shortening is an inherent
effect of treatment with anti-CD20 antibody in subjects that have had a
myocardial infarction. (See Ans. 2.) Because Barron teaches administering
anti-CD20 antibody to subjects who have had a myocardial infarction, it is
inherent that fractional shortening would occur, regardless of whether they
also have an autoimmune disease such as thrombocytopenia.
Appellants argue that the patient population of autoimmune
thrombocytopenia and the patient population suffering from myocardial
infarction are distinct, rather than overlapping. (See App. Br. 12.) In
support Appellants cite to a declaration by inventor Ziad Mallat. (See
Declaration Under 37 C.F.R. § 1.131 of Ziad Mallat ("Mallat Declaration").)
Dr. Mallat' s testimony4 does not support Appellants' argument. Dr. Mallat
testifies that only a small number (less than 4%) of patients admitted for
acute myocardial infarction display baseline thrombocytopenia, that only a
few (less than 7%) develop thrombocytopenia after myocardial infarction,
and that only a small percentage (less than 3%) of thrombocytopenia in the
setting of myocardial infarction is immune-mediated. (See Mallat Deel., ,r 4,
item 1.) Instead of contradicting it, Dr. Mallat' s testimony supports the
4 We note that Dr. Mallat refers to a reference (Chan et al., Pub. No.: US
2005/0163775 Al) that was not cited in the rejection that Appellants are
currently appealing. (See Mallat Deel. ,r 3.) We address the portions of the
declaration that are not specific to the prior art reference cited.
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Examiner's rejection by supporting the teaching in Barron that there are
myocardial infarction patients who develop thrombocytopenia. Dr. Mallat
testifies that there is overlap between autoimmune thrombocytopenia
patients and myocardial infarction patients, even if only by a small
percentage. Accordingly, Dr. Mallat supports the Examiner's finding that
those of ordinary skill in the art would have known to treat this population of
myocardial infarction patients with anti-CD20 antibody from the teachings
of Barron.
Appellants argue further that myocardial infarction is not a cause of
thrombocytopenia, citing several references5 in support. (See App. Br. 12-
13.) This argument is unpersuasive because the relevant issue is not whether
thrombocytopenia is always, or even usually, caused by myocardial
infarction. Rather, the relevant issue is whether the teachings of
administering anti-CD20 antibody to the patient populations taught in
Barron (patients suffering from thrombocytopenia as developed by
myocardial infarction) and in Shultz (patients suffering from ST segment
myocardial infarction) would have rendered Appellants' claimed methods
obvious.
5 Appellants provided copies of the supporting references in the Evidence
Appendix to the Appeal Brief, though internet accessing information was not
available. The references include: Mayo Clinic, Diseases and Conditions:
Thrombocytopenia (low platelet count); NIH, What Causes
Thrombocytopenia?; Johns Hopkins, Round 8: Autoimmune
Thrombocytopenia" by Thomas Kickier; McClure et al., Clinical
Significance ofThrombocytopenia During a Non-ST-Elevation Acute
Coronary Syndrome, Circulation, 99:2893-2900 (1999), and Brieger et al.,
Heparin-Induced Thrombocytopenia, 31 J. Am Coll Cardiol 1449-59
(1998).
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Appellants also argue that the knowledge in the art at the time taught
away from the claimed methods. (See App. Br. 13-14.) Specifically,
Appellants argue that B cells were thought to be cardioprotective and
atheroprotective and that, therefore, ordinarily skilled artisans would
not have considered depleting B cells as an effective treatment for
atherosclerosis and myocardial infarction. Appellants cite to Caligiuri 6;
Major7; and Goodchild8, in support. (See App. Br. 13.)
Appellants' argument and evidence are not persuasive because
Appellants do not point to specific teachings in the references cited that
indicate B cells should not be depleted when treating patients diagnosed with
an ischemic disorder with necrosis characterized by a myocardial infarction.
For example, Goodchild reports that "[i]ntramyocardial injection of B cells
into early post-ischemic myocardium preserved cardiac function by
cardiomyocyte salvage." (Goodchild, 1005.) In his declaration, Dr. Mallat
testifies that in light of Goodchild "one of ordinary skill in the art would not
have recognized the use of a B cell-depleting strategy as an effective
treatment for myocardial infarction." (Mallat Deel., ,r 4, item 3.) But failing
to recognize that a treatment would be effective is not the same thing as
teaching away from it. Appellants fail to direct us to a specific teaching in
Goodchild that an ordinarily skill artisan would have interpreted as
6 Caligiuri et al., Protective immunity against atherosclerosis carried by B
cells of hypercholesterolemic mice, 109 J. Clin. Invest. 745-753 (2002).
7 Major et al., B-Lymphocyte Deficiency Increases Atherosclerosis in LDL
Receptor-Null Mice, 22 Arterioscler Thromb Vase Biol.1892-1898 (2002).
8 Goodchild et al., Bone Marrow-Derived B Cells Preserve Ventricular
Function After Acute Myocardial Infarction, 2 JACC: Cardiovascular
Interventions 1005-1016 (2009).
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instructing not to administer anti-CD20 antibodies to myocardial infarction
patients at any time during their treatment. See In re Gurley, 27 F.3d 551,
553 (Fed. Cir. 1994) ("A reference may be said to teach away when a person
of ordinary skill, upon reading the reference, would be discouraged from
following the path set out in the reference, or would be led in a direction
divergent from the path that was taken by the applicant."). Instead, both
Barron and Shultz teach administering anti-CD20 antibodies to such
patients. See Medichem S.A. v. Rolabo S.L., 437 F.3d 1157, 1165 (Fed. Cir.
2006) ("obviousness must be determined in light of all the facts, and there is
no rule that a single reference that teaches away will mandate a finding of
nonobviousness. ").
Similarly, Appellants report that Caligiuri and Majors teach that B
cells are protective of atherosclerosis and can prevent atherosclerosis
lesions. (See App. Br. 13-14.) Again, Appellants do not direct us to
any teaching in either reference about anti-CD20 antibodies or about
administering agents to deplete B cells in myocardial infarction patients at
any time during their treatment. Instead, these references report experiments
in artificial rodent models lacking key proteins that are present in humans.
(See Ans. 8.) Accordingly, we are not persuaded that these references teach
away from Appellants' claimed methods.
Appellants argue that there would not have been a reasonable
expectation that the claimed method would be successful because another
reference, Millward,9 teaches that anti-CD20 antibody treatment was not
9 Millward et al., Cardiogenic shock complicates successful treatment of
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successful in treating thrombotic thrombocytopenia purpura, causing
biventricular cardiogenic shock in one patient. (See App. Br. 15-16; see
Reply Br. 3.) Appellants argue that because of the black box warning on the
anti-CD20 antibody, rituximab, ordinarily skilled artisans would not have
been motivated to use anti-CD20 antibodies in myocardial infarction
patients. (See id.) Although Millward reports an adverse effect in one
patient and reproduces the black box warning, Millward still concludes that
"[r]efractory TTP has been reported to respond favorably to rituximab when
used as an adjunct." (See Millward abstract.) Millward also reports that
"[n]o severe adverse reactions were noted in the previous 18 TTP patients
described." (Millward 1483; see Ans. 5.) Appellants do not direct us to a
teaching in Millward to abandon anti-CD20 antibodies in general. Rather
Millward teaches using caution when administering rituximab (see Millward
1483 ("Use of rituximab for refractory or relapsing TTP should follow a
careful assessment of potential benefits and risks.")) and the black box
warning instructs what should be done if adverse reactions do occur (see id.
1482 (discontinue infusion and provide medical treatment)). Accordingly,
we are not persuaded that Millward indicates Appellants' claimed methods
would not have been obvious.
Appellants fail to persuade us that the Examiner erred in rejecting the
pending claims as being obvious over the teachings of Barron and Shultz
under 35 U.S.C. § 103(a). Accordingly, we affirm the Examiner's rejection.
refractory thrombotic thrombocytopenia purpura with rituximab, 45
Transfusion, 1481-1486 (2005).
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Conclusion
Upon consideration of the record and for the reasons given, the
rejection of claims 8 and 12 under 35 U.S.C. § 103(a) is sustained.
Therefore, we affirm the decision of the Examiner.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.
AFFIRMED
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