Ex Parte Winkelstein et al

Patent Trial and Appeal Board

Jan 31, 2017

12582040 (P.T.A.B. Jan. 31, 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.
12/582,040 10/20/2009 Beth A. Winkelstein SEAPT14 3788
49691 7590
IP Strategies
P.O. Box 6446
Asheville, NC 28816
EXAMINER
MAHATAN, CHANNING S
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
02/02/2017 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):
thomas.champagne@ipstrategiespc.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BETH A. WINKELSTEIN, PAUL A. JANMEY,
and EVELYN S. SAWYER1
Appeal 2015-000403
Application 12/582,040
Technology Center 1600
Before JOHN G. NEW, RICHARD J. SMITH, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
appellants state the real party-in-interest is Sea Run Holdings. Inc. App.
Br. 2.
Appeal 2015-000403
Application 12/582,040
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Non-Final Rejection of claims 1—18 and 23—26. Specifically,
the claims stand rejected as unpatentable under U.S.C. § 112, first
paragraph, as lacking written descriptive support.
Claims 1, 2, 4—18, 23, and 24 also stand rejected as unpatentable
under U.S.C. § 103(a) as being obvious over the combination of Y-E. Ju et
al., Enhanced neurite growth from mammalian neurons in three-dimensional
salmon fibrin gels, 28 Biomaterials 2097—108 (2007) (“Ju”), Pauza et al.
(US 2006/0095016 Al, May 4, 2006) (“Pauza”), S.E. Michaud et al.,
Purification of Salmon Thrombin and its Potential as an Alternative to
Mammalian Thrombins in Fibrin Sealants, 107 Thrombosis Research
245—54 (2002) (“Michaud”) and/or L.Z. Wang et al., Purification of
Salmon Clotting Factors and Their Use as Tissue Sealants, 100
Thrombosis Research, 537-48 (2000) (“Wang”).
Claims 1—9, 16, 17, 23, and 24 also stand rejected as unpatentable
under U.S.C. § 103(a) as being obvious over the combination of Ju, Pauza,
and Q. Yin et al., Neurotrophin-4 Delivered by Fibrin Glue Promotes
Peripheral Nerve Regeneration, 24 Muscle Nerve 345—51 (2001) (“Yin”).2
2 The Examiner also rejected claims 1—7 and 9-18 as being unpatentable
under the nonstatutory doctrine of obviousness-type double patenting over
claims 1, 3, 5—7, 9-18, and 27—31 of Sawyer et al. US 8,771,684, July 8,
2014. See Office Act. 3, July 29, 2014. The Answer also includes claims 23
and 24 under this rejection, which we interpret as a new ground of rejection
entered by the Examiner. See Ans. 4. Because Appellants do not file a reply
or otherwise contest the double patenting rejection, we affirm the rejection
of claims 23 and 24as well. The Examiner states that the terminal
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Application 12/582,040
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM-IN-PART.
NATURE OF THE CLAIMED INVENTION
Appellants’ invention is directed to a method of alleviating central
nervous system-mediated pain [and] includes applying salmon thrombin at a
neural injury site. Applying salmon thrombin can include applying a gel that
includes salmon thrombin. The gel can also include fibrinogen, for example,
salmon fibrinogen, human fibrinogen, or bovine fibrinogen. The salmon
thrombin can be obtained from salmon plasma, or using recombinant
technology, or by fractionation. Abstract.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method of alleviating central nervous system-mediated
pain, comprising applying salmon thrombin at a neural injury
site, thereby diminishing a degree of nerve sensitivity to pain
experienced at the site.
App. Br. 147.
ISSUES AND ANALYSES
disclaimer filed by Appellants on July 15, 2013, is not complete (i.e., is
blank) and is therefore not approved. Appellants do not address this
rejection in their Appeal Brief. See Ans. 21. We consequently affirm the
Examiner’s rejection of these claims. See 37 C.F.R. § 41.37; see also Ex
parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (Informative)
(Arguments not raised in the Appellate Brief are considered waived).
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Application 12/582,040
We do not agree with the Examiner’s conclusion that claims 1—18 and
23—26 lack written descriptive support under 35 U.S.C. §112, first
paragraph. We agree with, and adopt, the Examiner that claims 1, 2, 4—18,
23, and 24 are obvious over the combination of Ju, Pauza, Wang, and
Michaud. We further agree with, and adopt, the Examiner’s findings and
conclusions with respect to these references and agree that claims 1—9, 16,
17, 23, and 24 are obvious over the combination of Ju, Pauza, and Yin. We
address the arguments raised on appeal by Appellants below.
A. Rejection of claims 1—18 and 23—26 for lack of written description
support under 35 U.S.C. § 112, first paragraph
Issue 1: Claims 1—18, 23, and 24
Appellants argue these claims separately, but present essentially the
same argument for each claim. See App. Br. 10-49. We consequently
consider these claims as argued together. Appellants argue the Examiner
erred in finding Appellants’ Specification does not provide written
descriptive support for the recitation of claim 1 reciting “diminishing a
degree of nerve sensitivity to pain experienced at the site.” App. Br. 10.
Analysis
Appellants argue the limitation reciting “diminishing a degree of
nerve sensitivity to pain experienced at the site” is described in Appellants’
Specification. App. Br. 11. By way of example, Appellants point to page 6
of the Specification, which discloses: “[IJnjection of salmon fibrinogen and
thrombin as a fibrin gel, reduces neuropathic pain after a painful nerve root
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Application 12/582,040
compression injury. Unexpectedly, we found that salmon thrombin alone,
but not human thrombin, produced even greater pain reduction.” Id.
The Examiner responds that the claim term “nerve sensitivity” is not
defined in Appellants’ Specification. Ans. 23. The Examiner finds the
reduction of neuropathic pain is different than “diminishing a degree of
nerve sensitivity to pain,” in which neuropathic pain occurs when there is
actual nerve damage (e.g., painful nerve root compression injury). The
Examiner finds “nerve sensitivity” does not require actual nerve damage. Id.
We are not persuaded by the Examiner’s findings. The Examiner
finds “[t]he reduction of neuropathic pain” is different than “diminishing a
degree of nerve sensitivity to pain.” See Ans. 23. However, Appellants’
Specification discloses:
[A] rat model of mechanical allodynia (behavioral sensitivity)
that is generally accepted as mimicking or correlating to human
neuropathic pain, and initiating sustained CNS responses that
regulate pain originating from injury to the CNS and PNS. We
show that injection of salmon fibrinogen and thrombin as a fibrin
gel, reduces neuropathic pain after a painful nerve root
compression injury. Unexpectedly, we found that salmon
thrombin alone, but not human thrombin, produced even greater
pain reduction.
Spec. 6 (internal references omitted). “Allodynia” is generally understood in
the art to mean “pain resulting from a stimulus (as a light touch of the skin)
which would not normally provoke pain.” “Allodynia” in Merriam-Webster
Medical Dictionary (2007). Furthermore, the Specification discloses:
Anesthetized male Sprague-Dawley rats (250-350g) were
subjected to a 15—25 minute compression of the C7 cervical
dorsal nerve root with a lOgf microclip, an established technique
that produces behavioral sensitivity that persists for 3-6 weeks
and mimics symptoms of persistent pain. Rats in both groups
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Application 12/582,040
were followed for seven days, during which time mechanical
allodynia was measured in the affected forepaw. Mechanical
allodynia was assessed by measuring frequency of paw
withdrawals after light touch.
Id. at 6—7 (internal references omitted).
Appellants’ Specification further discloses that: “Fig. 1A shows that
salmon fibrin (thrombin plus fibrinogen) alleviated a measure of pain
symptoms; reduction in sensitivity was significant and sustained.” Id. at 8.
Appellants’ Figure 1A is reproduced below:
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Appellants’ Figure 1A depicts mechanical allodynia in the
forepaw following nerve root compression, showing results
from treatment with salmon fibrin.
Appellants’ Specification and Figure 1A thus discloses “diminishing a
degree of nerve sensitivity to pain”; the results discloses by Figure 1A
demonstrate a decreased percentage of paw withdrawal (i.e., sensitivity to
perceived painful stimuli) in a generally accepted allodynic pain model,
upon treatment with salmon fibrin. We consequently reverse the Examiner’s
rejection of claims 1—18, 23, and 24.
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Application 12/582,040
Issue 2: Claim 25
In addition to the arguments presented above, Appellants also argue
that the Examiner erred in finding Appellants’ Specification fails to provide
support for the limitation of claim 25 reciting: “diminishing a degree of
nerve sensitivity to pain experienced at the site includes reducing an
inflammatory response.” App. Br. 50—51.
Analysis
The Examiner’s Answer does not address Appellants’ argument with
respect to claim 25. Moreover, in the Examiner’s Non-Final Rejection, the
Examiner makes only a conclusory finding that U.S. Provisional Patent
Application No. 61/111,828, filed on November 6, 2008 (the “’828
application”), to which Appellants’ present application claims the benefit
pursuant to 35 U.S.C. § 119(e), does not provide support for the disputed
limitation. Non-Final Act. 8.
We agree with Appellants’ that the Examiner’s findings are
insufficient to establish a prima facie case of insufficient written description
support. The Appellants’ Specification discloses:
Behavioral results showing decreased allodynia after
treatment with salmon thrombin alone or combined with salmon
fibrinogen given at the site of neural injury demonstrate that the
nociceptive and/or inflammatory response is mediated by the
salmon thrombin. The neural basal media also decreased
allodynia at later time points but to a lesser extent than did the
salmon proteins. Fig. 2 is a series of representative micrographs
showing EDI staining of macrophages at the C7 ipsilateral nerve
root at day 7 after sham controls, injury, and injury with salmon
fibrin (thrombin plus fibrinogen) treatment. As shown, treatment
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Application 12/582,040
with the salmon fibrin at the time of injury reduced EDI staining
compared to injury. The 100pm scale bar applies to all
micrographs.
Spec. 8 (quoting ’828 application 8,11. 14—22) (emphasis added). We agree
with the Examiner that the data disclosed in Appellants’ Specification thus
explicitly discloses that inflammatory responses are mediated by treatment
with salmon fibrinogen. Furthermore, we have explained supra our
reasoning with respect to why Appellants’ Specification also discloses
“diminishing a degree of nerve sensitivity to pain.” We consequently
reverse the Examiner’s rejection of claim 25.
Issue 3: Claim 26
In addition to the arguments presented above with respect to claims 1—
18, 23, and 24, Appellants also argue that the Examiner erred in finding
Appellants’ Specification fails to provide support for the limitation of claim
26 reciting: “diminishing a degree of nerve sensitivity to pain experienced at
the site includes reducing activation of microglia at the site.” App. Br. 52—
53.
Analysis
By way of example, Appellants point to page 9 of their Specification,
which discloses:
Fig. 3 is a chart showing the activation of microglia
(macrophages) by ibal staining and EDI staining in the spinal
cord adjacent to the injury site. As shown, the activation of
microglia shown by EDI staining is reduced after salmon
thrombin treatment. Similarly, density of activated microglia as
shown by ibal staining is reduced to sham levels.
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Application 12/582,040
App. Br. 53 (quoting Spec. 9).
The Examiner’s Answer does not address Appellants’ argument with
respect to claim 26. Moreover, in the Examiner’s Non-Final Rejection, the
Examiner finds merely that U.S. Provisional Patent Application No.
61/111,828, filed on November 6, 2008 (the “’828 application”), to which
Appellants’ present application claims the benefit pursuant to 35 U.S.C.
§ 119(e), does not provide support for the disputed limitation. Non-Final
Act. 8.
We agree with Appellants that the Examiner’s findings are
insufficient to establish a prima facie case of insufficient written description
support. We agree with the Appellants that the data disclosed in Appellants’
Specification explicitly discloses that inflammatory responses are mediated
by treatment with salmon fibrinogen. Furthermore, we have explained supra
our reasoning why Appellants’ Specification also discloses “diminishing a
degree of nerve sensitivity to pain.” We consequently reverse the
Examiner’s rejection of claim 26.
B. Rejection of claims E 2, 4—18, 23, and 24 under 35 U.S.C. $ 103(a)
Issue
Appellants argue the Examiner erred because the cited references fail
to teach or suggest a “method of alleviating central nervous system-mediated
pain, comprising applying salmon thrombin at a neural injury site,” as
recited in claim 1. App. Br. 64.
Analysis
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Application 12/582,040
Appellants argue the references cited by the Examiner relate to the
recovery of motor function and sensory perception following an injury.
App. Br. 64. Appellants point to Ju as teaching enhanced in vitro neurite
outgrowth of mammalian neurons in three-dimensional salmon thrombin
gels. Id. Appellants contend Ju does not address nociceptive perception at
all, but merely addresses neurite outgrowth and, in particular, axonal
regeneration for recovery from motor and sensory deficits. Id. Appellants
also argue Ju teaches that the outgrowth of neurites is not a function of the
salmon thrombin gel, but rather to the presence of fibrinogen and
fibronectin. Id. at 65.
Appellants dispute the Examiner’s finding that claim 1 does not
provide for aspects of the applied formulation that are distinguishable from
the formulation taught by Ju. App. Br. 65. According to Appellants, claim 1
recites “diminishing a degree of nerve sensitivity to pain experienced at the
site,” which, Appellants contend, is neither taught nor suggested by Ju. Id.
Appellants next argue that Pauza teaches treatment of a spinal disc
with a fibrin sealant to repair leakage. App. Br. 65. Appellants first contend
that Pauza is non-analogous art because it does not teach or suggest
treatment for the alleviation of pain. Id. Moreover, argue Appellants,
although Pauza teaches the use of an anesthetic for pain relief, the ultimate
pain relief taught by Pauza relates to repair of the disc, which in turn results
in the alleviation of the disc damage-induced pain. Id. at 65—66.
Appellants argue further that, although Pauza teaches the use of
thrombin generally as the active agent in the conversion to fibrin to
fibrinogen, Pauza does not explicitly teach or implicitly suggest the use of
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Application 12/582,040
salmon thrombin in the manner, and for the specific purpose, recited in
claim 1. App. Br. 68.
With respect to Wang and Michaud, Appellants argue both references
teach the use of salmon fibrinogen and thrombin in the creation of a sealant.
App. Br. 69. Neither reference, Appellants argue, teaches or suggests the
use of salmon thrombin in the alleviation of pain in the manner recited in
claim 1. Id.
The Examiner first observes that claim 1 recites a method “comprising
applying salmon thrombin at a neural injury site. Ans. 26. The
Examiner therefore finds that, because the step recites the term
“comprising,” the scope of the claim encompasses not only the application
of salmon thrombin but, additionally, the application of other compositions
together with salmon thrombin (e.g., salmon fibrin which includes salmon
thrombin and salmon fibrinogen; see claim 6). Id.
The Examiner finds Ju teaches the application of salmon fibrin, which
includes salmon thrombin, at neural injury sites within the CNS. Ans. 26
(citing Ju 2097—98). The Examiner finds the structural similarity between
the formulation or composition taught by Ju (e.g., salmon fibrin comprising
salmon thrombin and salmon fibrinogen) and the composition recited in he
claimed methods (e.g., claim 6; a gel that includes salmon thrombin and
salmon fibrinogen) is directed to a result and/or property (e.g., diminishing a
degree of nerve sensitivity to pain experienced at the site) of the
formulation/composition. Id. The Examiner points to Section 2112.02 of
the MPEP, which states:
The discovery of a new use for an old structure based on
unknown properties of the structure might be patentable to the
discoverer as a process of using. However, when the claim recites
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Application 12/582,040
using an old composition or structure and the “use” is directed to
a result or property of that composition or structure, then the
claim is anticipated.
Id. (internal citations omitted).
The Examiner finds that the application of salmon fibrin taught by Ju
would necessarily inhibit pain, based upon the structural similarities between
the formulation/composition taught by Ju and Appellants’ claims. Ans. 27
(citing MPEP § 2112.01 II). The Examiner also finds Appellants’ claims do
not describe any aspects of the applied formulation/composition that are
distinguishable from the formulation/composition that is taught by Ju (e.g.,
salmon fibrin comprising salmon thrombin and salmon fibrinogen). Id. The
Examiner therefore finds that a person of ordinary skill in the art would have
reasonably understood that the application of the described salmon fibrin
formulation of Ju necessarily alleviates pain. Id. The Examiner finds that,
although Ju is silent with respect to the limitation reciting, “diminishing a
degree of nerve sensitivity to pain experienced at the site,” the formulation
or composition found in Ju is structurally identical to that as instantly
claimed and, therefore, need not be recognized at the time of the invention.
Id. (citing MPEP §§ 2112 II, III; 2112.01 I, II; 2112.02).
With respect to claim 7, and the assertion that it is unknown whether
the Matrigel used in Ju is collagen, the Examiner finds Ju teaches that
Matrigel comprises collagen. Ans. 27. The Examiner finds Ju explicitly
states: “[W]e also cultured neurons in Matrigel, a commonly used three-
dimensional matrix enriched in laminin and collagen.” Id.
The Examiner next finds that Pauza teaches sequential/separate
application/injection of thrombin at a neural injury site and that a person of
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ordinary skill would therefore understand that thrombin (e.g., from salmon)
can be applied separately from fibrinogen at a neural injury site. Ans. 27
(citing Pauza 9, 16). The Examiner finds Pauza, in combination with Ju
and Michaud or Wang, teaches the application/injection of fibrin
compositions at a neural injury site and further teaches that fibrin
components (e.g., fibrinogen and thrombin) are readily obtainable from
salmon. Id. (citing Pauza 30, 31, 33, 37; Michaud Abstr.; Wang Abstr.).
We are not persuaded by Appellants’ arguments. Claim 1 requires
“comprising applying salmon thrombin at a neural injury site, thereby
diminishing a degree of nerve sensitivity to pain experienced at the site.” Ju
teaches:
Fibrin has been successfully utilized in repair strategies for
a variety of in vivo neuronal injury models. Fibrin has been used
as a glue to attach other grafting materials, as a matrix to provide
delivery of neurotrophic factors, and as a scaffold for
transplanted cells or to fill implanted guidance channels. In each
of these cases, fibrin was prepared from [fibrinogen] and
thrombin isolated from bovine or human sources.
Ju 2098.
Ju thus teaches that it was known in the art to employ thrombin as a
precursor to the formation of fibrin at sites of neural injury. Michaud and
Wang both teach the application of salmon thrombin as alternative to
mammalian thrombin. We agree with the Examiner that a person of
ordinary skill in the art would find it obvious to combine the teachings of the
references to arrive at the claim step of “applying salmon thrombin at a
neural injury site.” Furthermore, any additional unknown benefit (i.e.,
decreased sensitivity to painful stimuli) that would accrue as the result of
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that application does not suffice to render Appellants’ claimed invention
nonobvious over the combined cited prior art. See In re Woodruff, 919 F.2d
1575, 1578 (Fed. Cir. 1990) (“It is a general rule that merely discovering and
claiming a new benefit of an old process cannot render the process again
patentable”). We consequently affirm the Examiner’s rejection of these
claims.
C. Rejection of claims 1—9, 16, 17, 23, and 24 under 35 U.S.C. $ 103(a)
The Examiner relies upon Yin as teaching delivery of a neurotrophic
agent via a fibrin adhesive to promote peripheral nerve regeneration. Non-
Final Act. 26 (citing Yin Abstr.). The Examiner finds Yin teaches the
formulation of fibrin glue (e.g., composed of fibrinogen and thrombin) and
that application of fibrin to injured nerves of the peripheral nervous system
promotes nerve regeneration. Id. (citing Yin 346, 350; see also Ans. 31).
We are not persuaded by Appellants’ argument that the teachings of
Yin do not cure the deficiencies of the cited references that we have
explained supra. App. Br. 120. Yin explicitly teaches that thrombin and
fibrinogen are coinjected at the site of an induced neural injury and thus the
step of “comprising applying [...] thrombin at a neural injury site.” See Yin
346. We agree with Appellants that Yin does not explicitly teach the step of
“diminishing a degree of nerve sensitivity to pain experienced at the site”;
the “pinch test” taught by Yin is employed as an indicium of the extent of
neural regeneration, but does not directly relate to an increase or decrease in
sensitivity to painful stimuli. See Yin 346-47. Nevertheless, we find the
absence of this teaching to be irrelevant to this obviousness analysis. Yin
teaches the claim step of “applying salmon thrombin at a neural injury site,”
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and any additional unknown benefit (i.e., decreases sensitivity to painful
stimuli) that accrues or is observed as the result of that application does not
suffice to render Appellants’ claimed invention nonobvious over the
combined cited prior art. See Woodruff, 919 F.2d at 1578. We consequently
affirm the Examiner’s rejection of these claims.
DECISION
The Examiner’s rejection of claims 1—18 and 23—26 as unpatentable
under 35 U.S.C. §112, first paragraph, is reversed.
The Examiner’s rejection of claims 1, 2, 4—18, 23, and 24 as
unpatentable under 35 U.S.C. § 103(a) is affirmed.
The Examiner’s rejection of claims 1—9, 16, 17, 23, and 24 as
unpatentable under 35 U.S.C. § 103(a) is affirmed.
The Examiner’s rejection of claims 1—7, 9—18, 23, and 24 under the
nonstatutory doctrine of obviousness-type double patenting is affirmed (see
fn.2).
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(l)(iv).
AFFIRMED-IN-PART
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