Ex Parte Mishra

Patent Trials and Appeals Board

May 20, 2019

13889153 - (D) (P.T.A.B. May. 20, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/889, 153 05/07/2013
20995 7590 05/22/2019
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
FIRST NAMED INVENTOR
Allan Kumar Mishra
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.
BIOPAR.008Dl 3605
EXAMINER
SCHUBERG, LAURA J
ART UNIT PAPER NUMBER
1657
NOTIFICATION DATE DELIVERY MODE
05/22/2019 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):
j ayna.cartee@knobbe.com
efiling@knobbe.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ALLAN KUMAR MISHRA
Appeal2017-008314
Application 13/889,153
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and TA WEN CHANG,
Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134 involving claims to a
method of treating damaged connective tissue using a platelet rich plasma.
The Examiner rejected the claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
"[T]issue damage may be the result of injury, overuse, reduced blood
flow, or any other suitable cause. Even if the damage is halted or slowed, the
1 The Real Party in Interest is Allan Mishra (see Br. 2).
2 We have considered the Specification of May 7, 2013 ("Spec."); Final
Office Action of Aug. 13, 2015 ("Final Act."); Appeal Brief of Mar. 18,
2016 ("Br."); and Examiner's Answer of Sept. 13, 2016 ("Ans.").
Appeal2017-008314
Application 13/889,153
tissue may not completely heal due to the formation of degenerative,
immature, avascular, and scar tissue" (Spec. ,r 3). The Specification teaches
a "PRP [platelet rich plasma] composition may be used to treat tissue that
has been damaged due to injury, wound, trauma, lesion, and/or tissue
degeneration" (id. ,r 30). The Specification teaches a platelet rich plasma
"includes white blood cells and platelets at higher concentrations than those
in whole blood" (id.).
The Claims
Claims 1, 2, and 22-33 are on appeal. Claim 1 is the sole independent
claim, is representative, and reads as follows:
1. A method of treating damaged connective tissue comprising:
delivering a composition to a patient to treat the damaged
connective tissue comprising:
platelets in a concentration of about 500,000/µl to about
7,000, 000/ µl,
monocytes in a concentration of about 400/µl to about 3200/µl,
neutrophils in a concentration of less than about 5000/µl, and
lymphocytes in a concentration of about 2600/µl to about
16000/µl,
wherein the composition does not include an exogenous
activator.
The Rejection
The Examiner rejected claims 1, 2, and 22-33 under 35 U.S.C.
§ I03(a) as obvious over Mishra '382, 3 Mishra '193,4 Femandez, 5 and
3 Mishra, US 2006/0127382 Al, published June 15, 2006 ("Mishra '382").
4 Mishra, US 2005/0186193 Al, published Aug. 25, 2005 ("Mishra '193").
5 Fernandez et al., US 2008/0089867 Al, published Apr. 17, 2008
("F emandez").
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Application 13/889,153
Toner6 (Final Act. 6-8).
The Examiner finds Mishra '382 teaches "a method of making and
using neutrophil-depleted platelet rich plasma ... for the treatment of
connective tissue injury" (Final Act. 6). The Examiner finds Mishra '382
teaches the "neutrophil portion of the composition is taught to be
advantageously depleted by more than 7 5% ... and the platelets are taught
to be in the range of 500,000 to 1,200,000 per cubic millimeter" (id.).
The Examiner acknowledges "Mishra '382 is silent with regard to the
actual concentration ranges of the monocytes, lymphocytes and neutrophils .
. . . While Mishra '382 does require removal of neutrophils he does not
require the removal of lymphocytes or monocytes" (Final Act. 7).
The Examiner finds Mishra '193 teaches "using an autologous platelet
rich plasma composition (PRP) for the treatment of tissue injury" and the
PRP "is taught to contain concentrated numbers of white blood cells" (Final
Act. 7). The Examiner finds Fernandez teaches "that blood monocytes and
lymphocytes are present at increased concentrations in the PRP and provide
beneficial features such as additional healing cytokines while providing
antibacterial activity" (id.). The Examiner finds Toner teaches "normal
concentrations of white blood cells in whole blood include 1500
lymphocytes/µl, 480 monocytes/µl and 3720 total neutrophils/µl" (id.).
The Examiner finds it obvious "to increase the normal concentrations
of monocytes and lymphocytes in the composition of Mishra [']382 because
Mishra ['] 193 and Fernandez et al. both suggest that white blood cells
provide a beneficial feature to PRP in the form of protection against
6 Toner et al., US 2006/0134599 Al, published June 22, 2006 ("Toner").
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Application 13/889,153
infection and increased healing cytokines" (Final Act. 8). Therefore, the
Examiner also finds it obvious "to optimize the concentrations of
monocytes, lymphocytes and neutrophils because these components are
known in the prior art to be result effective variables" (id. at 7-8).
The issues with respect to this rejection are:
(i) Does a preponderance of the evidence of record support the
Examiner's conclusion that Mishra '382, Mishra '193, Fernandez, and Toner
render the method of claim 1 obvious?
(ii) If so, has Appellant presented evidence of secondary
considerations that, when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness?
Findings of Fact
1. Mishra '382 teaches "introducing a neutrophil-depleted platelet-
rich plasma composition into and around the site of tissue injury. In
preferred embodiments, the tissue is connective tissue" (Mishra '382 ,r 14).
2. Mishra '382 teaches that neutrophils are "attracted to dyes that
do not have a positive or negative charge. Therefore, they are neutral.
Platelets and other white blood cells such as monocytes and lymphocytes,
conversely, have a negative surface membrane charge" and therefore "by
forcing a blood, platelet or platelet rich plasma fraction through a narrow,
twisted and/or charged environment, neutrophils are preferentially removed
from other blood components" (Mishra '382 ,r,r 31-32).
3. Mishra '3 82 teaches that in "a most preferred embodiment, the
neutrophils in the platelet rich plasma or whole blood are depleted by more
than 75%" (Mishra '382 ,r 46).
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Application 13/889,153
4. Mishra '382 teaches that "[t]ypically, platelet counts range from
500,000 to 1,200,000 per cubic millimeter, or even more. PRP is formed
from the concentration of platelets from whole blood" (Mishra '382 ,r 54).
5. Mishra '382 teaches "the neutrophil-depleted platelet-rich
plasma or neutrophil-depleted whole blood composition is substantially free
from exogenous activators" (Mishra '382 ,r 52).
6. Mishra '193 teaches "platelet compositions may be used to
promote vascularization and/or revascularization of injured tissue and
treatment of incomplete repair of various connective tissues" (Mishra '193
i1 46).
7. Mishra '193 teaches "[ t ]ypically, platelet counts in PRP as
defined herein range from 500,000 to 1,200,000 per cubic millimeter"
(Mishra '193 ,r 54).
8. Mishra' 193 teaches the "APEX [autologous platelet extract]
typically has a concentrated number of white blood cells along with
platelets. This combination of white blood cells and platelets either controls
or eliminates an infection" (Mishra '193 ,r 128).
9. Fernandez teaches "[in m]ethods of making an autologously
derived-platelet gel ... it is common to achieve platelet counts in excess of
over three to five times baseline counts" (Fernandez ,r 43).
10. Fernandez teaches "[w]hile white cell content increases 125%
with selection for lymphocytes and monocytes, the inclusion of platelets and
white cells appears to have several beneficial aspects. For example, white
cells confer additional healing cytokines while providing antibacterial
activity" (Fernandez ,r 43).
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Appeal2017-008314
Application 13/889,153
11. Table 1 of Toner is reproduced below:
TABLE l
Types, concentrations, .rnd sizes of blood cells,
Cell Type
Red blood cells (RBC)
Segmented Neutrophils
(\VBC")
Band Nentrophils
(\VBC,i
Lymphocytes (\VBC)
Monocytes (WBC)
Eosinophils (WBC)
Basophils (WBC)
Platelets
l•et:Ll Nucleated Red
Blood Cells
Concentration kells/pJ)
4,2 6, 1 X } 06
3600
120
15(1(1
480
J80
l20
500 X 103
2--50 X 10--J
Size (~un)
46
>10
>10
::-10
;,.10
>10
>10
1--2
8--12
Table 1 discloses normal concentrations of cells in circulating blood (Toner
if 59).
Principles 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."
KSR International Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If a
person of ordinary skill can implement a predictable variation, § 103 likely
bars its patentability." Id. at 417.
Prima facie obviousness can be rebutted by presenting evidence of
secondary considerations and, when such evidence is submitted, all of the
evidence must be considered anew. In re Piasecki, 745 F.2d 1468, 1472-
1473 (Fed. Cir. 1984).
Analysis
We adopt the Examiner's findings regarding the scope and content of
the prior art (Final Act. 6-8) and agree that claim 1 would have been
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Application 13/889,153
obvious in view of Mishra '382, Mishra '193, Fernandez, and Toner (FF 1-
11 ). We address Appellants arguments below.
Prima facie obviousness
Appellant contends
Mishra [']193, Fernandez, and Toner do not disclose or suggest
the features and concentrations as claimed in claim 1. The
claims are directed to a composition comprising platelets at a
high level (500,000/µl to about 7,000,000/µl) in which levels of
neutrophils have been depleted (to a concentration of less than
about 5000/µl) while maintaining levels of other components of
white blood cells as indicated by the recited range of
"monocytes in a concentration of about 400/µl to about
3200/µl" and "lymphocytes in a concentration of about 2600/ µl
to about 16000/ µl."
(Br. 7).
We are not persuaded. Mishra '382 and Mishra '193 both teach
methods of treating damaged connective tissue using compositions with
elevated amounts of platelets in amounts overlapping the range recited in
claim 1 (FF 1, 4, 6, 7). Mishra '382 teaches a 75% depletion ofneutrophils
(FF 3) which results in amounts within the range recited in claim 1 as
evidenced by Toner (FF 11 ).
As to the amounts of monocytes and lymphocytes, Toner teaches
amounts normally found in blood overlap or are close to the recited ranges
for monocytes and lymphocytes, respectively (FF 11 ). Mishra '193 provides
reasons to use elevated amounts (i.e. "a concentrated number") of white
blood cells such as monocytes and lymphocytes to control or eliminate
infection (FF 8). Similarly, Fernandez also provides reasons to use
compositions where "white cell content increases ... with selection for
lymphocytes and monocytes" because these "white cells appears to have
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Appeal2017-008314
Application 13/889,153
several beneficial aspects. For example, white cells confer additional
healing cytokines while providing antibacterial activity" (FF 10).
Thus, we find that the prior art directly suggests the use of a
composition with platelets and neutrophils in amounts overlapping those
recited in claim 1, and reasonably suggests optimizing the amounts of
monocytes and lymphocytes, already normally present in amounts
overlapping or close to those recited in claim 1, to amounts consistent with
those recited in claim 1 (FF 1-11 ). "[D]iscovery of an optimum value of a
result effective variable in a known process is ordinarily within the skill of
the art." In re Boesch, 617 F.2d 272, 276 (CCPA 1980).
Secondary Considerations
Appellant contends that Exhibits A---C demonstrate unexpected results
(see Br. 8). In particular, Appellant contends "Exhibit A demonstrates an
unexpected effect in treatment of a connective tissue disorder (tennis elbow)
over a control group which received the same treatment protocol but with
bupivacaine as the active agent instead of platelet-rich plasma" (id.).
Appellant contends Exhibit B "describes an unexpected effect in
administration of PRP in treatment of another type of connective tissue
injury - Achilles tendinosis" (id.). Appellant contends
(Id.).
Exhibit C demonstrates a difference between neutrophil-
depleted PRP ("PRP 2.0") in which neutrophils were depleted
to a level of 739/µl, and PRP 1.0 with a neutrophil average of
19598/µ1. PRP 2.0 corresponds to the composition of present
claim 1 on appeal. Neutrophil-depleted PRP 2.0 was more
effective to promote recovery from myocardial infarction in a
swine model.
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Application 13/889,153
We find this evidence unavailing for several reasons. First, the
exhibits in the Mishra Declaration 7 do not compare their compositions with
the closest prior art, which would be the composition of Mishra '382. In
Exhibit A, the experiment compared a particular platelet rich plasma
composition to bupivacaine, not to the composition of Mishra '382 (see
Exhibit A at 1 ). In Exhibit B, the experiment did not compare the platelet
derived plasma composition to any other composition (see Exhibit B at 1 ).
In Exhibit C, there was a comparison between two different platelet rich
plasma compositions (see Exhibit C at 1 ), but again, the PRP 2.0 was
compared to a PRP 1.0 composition with elevated levels of neutrophils
relative to the amount normally found in blood as shown by Toner (FF 11 ),
not to a composition having reduced amount of neutrophils as expressly
taught by Mishra '382 (FF 3).
Thus, none of the evidence in the Exhibits demonstrates that the
claimed compositions is unexpected relative to the closest prior art of Mishra
'382. See In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991)
("[W]hen unexpected results are used as evidence of nonobviousness, the
results must be shown to be unexpected compared with the closest prior
art.").
Second, the results are not commensurate in scope with the scope of
claim 1, which recites broad ranges for the platelets, monocytes, neutrophils
and lymphocytes. The results in Exhibits A---C are limited to, at most, three
particular compositions, and the amounts of platelets, monocytes, and
lymphocytes are not provided for any of these compositions. Exhibit C does
7 Declaration of Dr. Allan Mishra, dated July 26, 2015.
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Application 13/889,153
give a single reduced neutrophil level of 739/µl, but does not provide
evidence commensurate in scope with the much broader recitation in claim 1
of "less than about 5,000/µl" for neutrophils.
Thus, the evidence is not commensurate in scope with the recitations
in claim 1. Unexpected results must be "commensurate in scope with the
degree of protection sought by the claimed subject matter." In re Harris,
409 F.3d 1339, 1344 (Fed. Cir. 2005).
Conclusion of Law
(i) A preponderance of the evidence of record supports the
Examiner's conclusion that Mishra '382, Mishra '193, Fernandez, and Toner
render the method of claim 1 obvious.
(ii) Appellant has not presented evidence of secondary
considerations that, when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness.
SUMMARY
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
obvious over Mishra '382, Mishra '193, Fernandez, and Toner. Claims 2
and 22-33 fall with claim 1.
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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