Ex Parte Blau et al

Patent Trial and Appeal Board

May 23, 2017

13440534 (P.T.A.B. May. 23, 2017)

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.
13/440,534 04/05/2012 Helen M. Blau STAN-829 6495
77974 7590 05/25/2017
Stanford University Office of Technology Licensing
Bozicevic, Field & Francis LLP
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
EXAMINER
VISONE, THOMAS J
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
05/25/2017 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):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HELEN M. BLAU, BENJAMIN D. COSGROVE, and
PENNEY M. GILBERT
Appeal 2016-005788
Application 13/440,534
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
Appeal 2016-005788
Application 13/440,534
STATEMENT OF CASE
The following claims are representative.
1. A method for improving the ability of aged,
muscle satellite cells to regenerate muscle tissue in an
individual human past the age 50 years or mouse past 22
months of age, the method comprising:
identifying an aged individual mouse or human;
contacting aged muscle satellite cells from said aged
individual with an inhibitor of p38 mitogen-associated protein
kinase (MAPK);
wherein said the aged muscle satellite cells are induced to
proliferate and regenerate said tissue.
4. The method according to Claim 1, wherein said inhibitor of
p38 MAPK is administered locally or systemically to the individual.
16. A method for improving the ability of aged human or mouse
muscle satellite cells to regenerate muscle tissue in response to injury,
the method comprising:
identifying an aged individual mouse or human past the age 50
years in a human or 22 months in a mouse;
contacting a population of aged human or mouse muscle satellite
cells obtained from an the aged individual, in an ex vivo culture on a
pliable substrate with an inhibitor of p38 mitogen associated protein
kinase (MAPK) in a dose and for a time sufficient to expand the
number of muscle satellite cells in the population;
wherein the expanded population of aged muscle satellite cells
has an enhanced ability to regenerate muscle tissue relative to
untreated aged muscle satellite cells.
18. The method of Claim 16, wherein said pliable substrate is a
hydrogel.
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Application 13/440,534
Grounds of Rejection
1. Claims 1—2, 4—5, 13, 16, 20, and 26 are rejected under pre-AIA 35
U.S.C. §103(a) as being unpatentable over Underhill (WO
02/094842 A2; pub. Nov. 28, 2002).
2. Claims 18 is rejected under 35 U.S.C. § 103(a) as being
unpatentable over Underhill and Cosgrove (Benjamin D.
Cosgrove, A home away from home: challenges and opportunities
in engineering in vitro muscle satellite cell niches, NIH Public
Access Author Manuscript, Author manuscript available in
Differentiation, 2009; 782(2—3).
FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Final Action at
pages 2—7. The following facts are highlighted.
1. Underhill teaches a method that can be used to regenerate muscle in a
variety of subjects such as fetuses, newborns, children, and adults.
(Page 27, lines 26—29). More particularly, Underhill teaches the
method can be used to treat late-adult onset Welander distal myopathy
and repair or replace, i.e., regenerate, muscle tissue (Pages 27—29).
2. Underhill states that
In another embodiment, the muscle atrophy results from chronic
disuse. Such disuse atrophy may stem from conditions including, but
not limited to: paralysis due to stroke, spinal cord injury; skeletal
immobilization due to trauma (such as fracture, sprain or dislocation)
or prolonged bed rest. In yet another embodiment, the muscle atrophy
results from metabolic stress or nutritional insufficiency, including,
but not limited to, the cachexia of cancer and other chronic illnesses,
fasting or rhabdomyolysis, endocrine disorders such as, but not
limited to, disorders of the thyroid gland and diabetes.
p. 32.
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3. Underhill states that its p38 mitogen activated protein kinase (MAPK)
inhibitor compounds may be administered systemically or topically.
P.38.
4. Underhill recognizes the myogenic potential of progenitor cells in any
phase of development, including aged cells, can be enhanced through
p38 MAPK inhibition. Final Act. 3.
5. Underhill explicitly teaches that “inhibition of p38 MAPK activity
results in enhanced myogenesis of myogenic precursors.” (Page 3,
lines 21—23). The starting cells and method steps taught by Underhill
are indistinguishable from those of the claimed invention. Id.
6. According to the Specification, “Muscle tissue in adult vertebrates
regenerates from stem cells known as satellite cells. Satellite cells are
distributed throughout muscle tissue and are mitotically quiescent in
the absence of injury or disease, residing in an instructive,
anatomically defined niche.” Spec. 1.
7. According to Appellants’ Specification, page 3,
In one embodiment of the invention, a subject who is in need of tissue
rejuvenation, e.g. due to an injury, disease, or aging, is contacted with
an inhibitor of the p38 mitogen associated protein kinase (MAPK)
signaling pathway in a dose effective to stimulate rejuvenation and
proliferation of stem cells resident in the targeted tissue. Included as
inhibitors of interest are molecules that selectively inhibit p38 MAPK,
a component of the MAPK signaling pathway, or a component
upstream or downstream of the MAPK signaling pathway. Inhibitors
of interest may be small molecules, polynucleotides, antibodies,
antagonist proteins, and the like. Inhibitors of interest include,
without limitation, small molecule inhibitors of the a and P isoforms
of p38 MAP kinase, e.g. SB202190, SB203580, etc. Delivery of the
inhibitor may be systemic or localized, usually localized.
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8. According to the Specification, “In some embodiments, the tissue is
muscle tissue. Resident in muscle tissue are satellite cells, which are
stem cells that ultimately give rise to muscle fibers. Satellite cells in
aged muscle are rejuvenated and capable of regeneration of tissue
when the p38 MAPK signaling pathway is inhibited.” Spec. 3.
PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
“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).
Obviousness Rejection 1
Appellants do not provide separate arguments for individual claims.
We select claims 1 and 18 as representative of rejections 1 and 2,
respectively. According to the Examiner,
Underhill teaches a method of regenerating muscle tissue
comprising contacting myogenic progenitor cells with a p38
(e.g., alpha and beta isoforms) MAPK inhibitor to induce
myogenesis and then administering the cells to a subject. (Page
2, lines 13-34; page 5, lines 25- 27; page 10, lines 16-25; page
3, lines 21-32; and pages 26-28). Alternatively, Underhill
teaches the p3 8 MAPK inhibitor can be directly administered to
a subject’s tissue in order to induce the myogenic progenitor
cells residing in the tissue. (Page 26, lines 15-30; and page 37,
lines 24-34)[.]
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Underhill teaches the precursors may be stimulated to
proliferate using, e.g., BMP-4 or any other known growth or
proliferative factor for myogenic progenitors. (Page 28, lines
11-12).
Underhill also teaches the treatment can be administered
by orally, by parenteral administration by injection, or by IM
injection. (Pages 37-40). Underhill teaches the myogenic
progenitor cells can be cultured on pliable substrates and
subsequently transplanted into a subject. (Pages 28-29). It is
noted that Underhill broadly defines “myogenic progenitor” and
“myogenic precursor” cells as any cell that is capable of
becoming confined to the muscle fate or giving rise to a
descendent cell confined to the muscle fate. (Page 5, lines 25-
28).
Underhill does not explicitly teach the muscle tissue is
from an individual human or mouse past the age 50 years in a
human or past 22 months in a mouse.
Final Act. 2—3.
Appellants contend that, “Underhill cannot render the claims . . .
obvious at least because Underhill fails to teach or suggest a limitation of
Claim 1, namely contacting aged muscle satellite cells of an aged individual
with an inhibitor of p38 MAPK.” App. Br. 4.
Appellants further contend that,
the Examiner has erred in his interpretation of how an
ordinary skilled artisan would interpret the teachings of
Underhill. Underhill describes at length how prior studies
performed in cells derived from satellite cells showed that
“activation of p38 MAPK stimulates myogenesis” (see e.g., pg.
3, line 24-29; emphasis added). In addition, as described
above, the specifically described embodiments of Underhill are
restricted to the application of p38 MAPK inhibitor to
developing embryonic limbs. Underhill, however, does not
suggest that the findings made in studying embryonic cells
somehow translate to adult satellite cells. In fact, Underhill
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Application 13/440,534
suggests the opposite, stating that satellite cells are important in
“a program that differs from the embryonic myogenic
program ” (pg.5, lines 10-11; emphasis added).
Furthermore, Underhill suggests that the myogenesis
promoting effect of p3 8 MAPK inhibitor is not even consistent
in embryonic cell types across different conditions.
App. Br. 5.
ANALYSIS
We agree with the Examiner’s fact finding, statement of the rejection
and responses to Appellants’ arguments as set forth in the Answer. We find
that the Examiner has provided evidence to support a prima facie case of
obviousness. We provide the following additional comment to the
Examiner’s argument set forth in the Final Rejection and Answer.
We are not persuaded by Appellants’ arguments. During ex parte
prosecution, claims are to be given their broadest reasonable interpretation
consistent with the description of the invention in the specification. See In re
Zletz, 893 F.2d 319, 321 (Fed. Cir. 1989).
Appellants’ claims encompass administering an inhibitor of the p38
mitogen associated protein kinase (MAPK) systemically to an adult. FF7,
claim 4. Appellants’ Specification states that, “the tissue is muscle tissue.
Resident in muscle tissue are satellite cells, which are stem cells that
ultimately give rise to muscle fibers. Satellite cells in aged muscle are
rejuvenated and capable of regeneration of tissue when the p38 MAPK
signaling pathway is inhibited.” FF8.
Underhill discloses administering an inhibitor of the p38 mitogen
associated protein kinase (MAPK) systemically to adults with muscle
atrophy. In particular, to adults with muscular atrophy conditions that are
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often associated with aging, e.g, stroke, diabetes, etc. FF1, 2. Because
satellite cells are resident in muscle tissue, the administration of an inhibitor
of the p38 mitogen associated protein kinase (MAPK) systemically to adults
with muscle atrophy in Underhill, necessarily meets the method limitations
claimed, as muscle tissue will be exposed to the systemically administered
inhibitor of the p38 mitogen associated protein kinase (MAPK) in Underhill
(cf Instant claim 5).
In addition, based on the Examiner’s argument on page 5 of the
Answer, we agree with the Examiner that, “muscle satellite cells, i.e., muscle
stem cells that progress through the myogenic linage to give rise to
terminally differentiated muscle tissue, are consistent with the definition of
myogenic progenitors and myogenic precursors taught by Underhill.” The
Examiner further finds that, “Applicant discloses that ‘[mjuscle tissue in
adult vertebrates will regenerate from reserve myoblasts called “satellite
cells”.’ (10087). Indeed, Underhill even teaches contacting myocytes, in
addition to, precursors of myocytes, such as mesenchymal cells or
myoblasts, with a p38 MAPK inhibitor. (See, e.g., page 27, lines 30-33).”
Ans. 7.
Appellants’ argue that
the specifically described embodiments of Underhill are
restricted to the application of p3 8 MAPK inhibitor to developing
embryonic limbs. Underhill, however, does not suggest that the
findings made in studying embryonic cells somehow translate to adult
satellite cells. In fact, Underhill suggests the opposite, stating that
satellite cells are important in “a program that differs from the
embryonic myogenic program” (pg.5, lines 10-11; emphasis added).
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App. Br. 5. Notwithstanding this argument, Underhill describes the
administration of an inhibitor of the p38 mitogen associated protein kinase
(MAPK) systemically to adults with muscle atrophy. FF1,2. Thus,
Underhill describes administration to muscle tissue and therefore also to
muscle satellite cells.
We further agree with the Examiner that the age of 50 years recited in
the preamble of the claim appears arbitrary, and is reasonably disclosed by
Underhill.
According to the Specification, page 16,
Aged. As used herein, the term aged refers to the effects
or the characteristics of increasing age, particularly with respect
to the diminished ability of somatic tissues to regenerate in
response to damage, disease, and normal use. One measure of
aging, therefore, is evidenced by the intrinsic lack of ability of
somatic stem cells to regenerate tissues. Alternatively, aging
may be defined in terms of general physiological
characteristics. The rate of aging is very species specific, where
a human may be aged at about 50 years; and a rodent at about 2
years. In general terms, a natural progressive decline in body
systems starts in early adulthood, but it becomes most evident
several decades later. One arbitrary way to define old age more
precisely in humans is to say that it begins at conventional
retirement age, around about 60, around about 65 years of age.
Another definition sets parameters for aging coincident with the
loss of reproductive ability, which is around about age 45, more
usually around about 50 in humans, but will, however, vary
with the individual.
Furthermore, “Underhill teaches the method can be used to regenerate
muscle in a variety of subjects such as fetuses, newborns, children, and
adults. (Page 27, lines 26-29). More particularly, Underhill teaches the
method can be used to treat late-adult onset Welander distal myopathy and
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Application 13/440,534
repair or replace, i.e., regenerate, muscle tissue (Pages 27-29).” Ans. 3.
Because the disclosure of adults in Underhill reasonably includes 50 year old
adults, the obviousness rejection is affirmed for the reason of record.
Appellants provide no evidence that “adults” would not have been
understood by those of ordinary skill in the art to include 50 year old adults.
See also FF 1,2.
Appellants present similar arguments for rejection 2 as for rejection 1.
Brief 8. For rejection 2, Cosgrove is additionally relied upon by the
Examiner for the disclosure
that hydrogels “are largely resistant to nonspecific cell adhesion
mediated by protein adsorption and allow for experimentally
determined presentation of ligands, through either covalent or non-
covalent (e.g., streptavidin-biotin) binding chemistries, to facilitate
cell adhesion through specific protein modifications.’’(Page 191).
Cosgrove also teaches that “of particular interest for the in vitro
maintenance of satellite cells are the widely-used poly(ethyleneglycol)
(PEG)-based hydrogels, which have both tunable matrix stiffness and
controlled ligand tethering for inducing receptor activation and cell
adhesion.” (Page 191).
Final Act. 4. We did not find Appellants’ arguments for rejection 1
convincing. Rejection 2 is affirmed for the reasons of record.
CONCLUSION OF LAW
The cited references support the Examiner’s obviousness rejections,
which are affirmed for the reasons of record. All pending, rejected claims
fall.
AFFIRMED
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