Ex Parte Vanderby et al

Board of Patent Appeals and Interferences

Sep 24, 2010

11431347 (B.P.A.I. Sep. 24, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________________

Ex parte RAY VANDERBY
and
KELLEY W. GRORUD,
Appellants1
____________________

Appeal 2010-002040
Application 11/431,347
Technology Center 1600
____________________

Before CHUNG K. PAK, CAROL A. SPIEGEL, and JEFFREY T. SMITH,
Administrative Patent Judges.

SPIEGEL, Administrative Patent Judge.

DECISION ON APPEAL2

1 The real party in interest is the WISCONSIN ALUMNI RESEARCH
FOUNDATION (Appellant's Appeal Brief filed 26 May 2009 ("App. Br.")
at 2. This decision also cites the Examiner's Answer mailed 4 September
2009 ("Ans."), Appellant's Reply Brief filed 4 November 2009 ("Reply Br."),
and the Specification ("Spec.") of Application 11/431,347 ("the 347
Application").
2 The two-month period for filing an appeal or commencing a civil action, as
recited in 37 C.F.R. § 41.52, begins to run from the "MAIL DATE" (paper
delivery mode) or the "NOTIFICATION DATE" (electronic delivery mode)
shown on the PTOL-90A cover letter attached to this decision.
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Appellants appeal under 35 U.S.C. § 134(a) from an Examiner's final
rejection of all pending claims, claims 1, 4-7, 9, and 10 (App. Br. 2; Ans. 2).
We have jurisdiction under 35 U.S.C. § 134. We AFFIRM-IN-PART.
I. Statement of the Case
The subject matter on appeal is directed to methods of treating
traumatic cartilage injury and improving the strength of a damaged cartilage
or bone by administering an effective amount of one or more of eleven
specifically recited neuropeptides. Claims 1 and 7 are illustrative and read
(App. Br. 12):
1. A method of treating traumatic cartilage
injury, the method comprising administering to the
subject an amount of a neuropeptide selected from
the group consisting of calcitonin gene-related
peptide (CGRP), cholecystokinin (CCK), dynorphin,
enkephalin, galanin, neuropeptide Y (NPY),
neurotensin, somatostatin, substance P (SP),
thyrotropin-releasing hormone (TRH), vasoactive
intestinal peptide (VIP), and combinations thereof,
the amount being effective to stimulate repair of the
injured cartilage or bone.[3]

7. A method of improving the strength of a
damaged cartilage or bone, the method comprising
administering to a subject having a damaged
cartilage or bone a cartilage or bone strength-
improving amount of a neuropeptide selected from
the group consisting of calcitonin gene-related
peptide (CGRP), cholecystokinin (CCK), dynorphin,
enkephalin, galanin, neuropeptide Y (NPY),
neurotensin, somatostatin, substance P (SP),
thyrotropin-releasing hormone (TRH), vasoactive
intestinal peptide (VIP), and combinations thereof.

3 We note that the preamble only refers to injured cartilage.
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Claim 4 requires the neuropeptide administered in claim 1 to be so in
combination with a pharmaceutically suitable carrier. Claims 5 and 9 limit
the subject being treated in claims 1, 4, and 7 to a mammal, while claims 6
and 7 limit the subject to a human.
The Examiner rejected claims 1, 4-7, 9, and 10 under 35 U.S.C. § 112,
first paragraph, as not enabled for the full scope of the claimed invention;
and, claims 7, 9, and 10 under 35 U.S.C. § 102(b) as anticipated by
Delgado.4 We reverse the rejection under § 112, first paragraph, and sustain
the rejection under § 102(b).
II. Scope of Enablement
A. Introduction
The Examiner rejected claims 1, 4-7, 9, and 10 as unpatentable under
35 U.S.C. § 112, first paragraph, as failing to enable the full scope of the
claimed invention (Ans. 3-8). According to the Examiner, the Specification
is only "enabled for improving healing of a damaged cartilage or bone by
administering CGRP, SP, VIP or NPY to a subject having a damaged
cartilage or bone" (Ans. 6).
Essentially, the position of the Examiner is that
the specification only shows the effects of CGRP,
NPY, SP and VIP in vitro and SP in vivo in
examples 8-9. The specification fails to teach the
structural and functional relationship among
different neuropeptides and their cognate receptors.
The structural and functional correlation between
the rest of the claimed neuropeptides and the
claimed invention is unknown. Thus, the claims are

4 Delgado et al., Vasoactive intestinal peptide prevents experimental arthritis
by downregulating both autoimmune and inflammatory components of the
disease, 7 NATURE MEDICINE 563-568 (2001) ("Delgado").
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not enabled for all of the claimed neuropeptides …
Since the effects of the other neuropeptides are not
known, it is also unpredictable whether the rest of
the claimed neuropeptides have the effects on
treating traumatic cartilage or bone injury in vivo.
Appellant cannot treat traumatic injury based on
unknown function or knowledge of the rest of the
claimed neuropeptides and their receptors in
different tissues. Note that a patent is granted for a
completed invention, not the general suggestion of
an idea and how that idea might be developed into
the claimed invention. … Genentec, Inc, v. Novo
Nordisk, 42 USPQ 2d 100,(CAFC 1997) [sic], … .
(Ans. 14.)

The Examiner relies on Schaffer5 and Elefteriou6 for support (Ans. 6, 11-12).
However, as pointed out by Appellants, the Examiner "has explicitly
taken the position that CGRP has 'similar biological activities and
properties,' to SP, VIP, and NPY" (App. Br. 7). Appellants also point out
that "the in vivo data, coupled with the in vitro data, clearly establishes the
pharmacological activity of the recited compounds to treat damaged bone
and cartilage" (id. at 8). "Regarding both Claims 1 and 7, Applicants note
that efficacy to promote the growth of cultured chondrocytes is
unquestionably correlated with improving the strength of damaged cartilage
– autologous chondrocyte transplantation is now a commercially available
procedure", citing Carticel for support7 (id. at 9).

5 Schaffer et al., Neuropeptides: Mediators of Inflammation and Tissue
Repair?, 133 ARCHIVES OF SURGERY 1107-1116 (October 1998) ("Schaffer").
6 F. Elefteriou, Review: Neuronal signaling and the regulation of bone
remodeling, 62 CELLULAR AND MOLECULAR LIFE SCIENCES 2339-2349
(2005) ("Elefteriou").
7CARTICEL: How CARTICEL® Can Help, downloaded 25 April 2008
from http://www.carticel.com/patients/treating/how-carticel-can-help.aspx.
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At issue, therefore, is whether the evidence of record supports a
determination that treatment of damaged cartilage or bone with the
neuropeptides CGRP, SP, VIP and NPY is reasonably extrapolated to the
rest of the neuropeptides recited in the Markush group of the method claims
on appeal or not.
B. Findings of fact ("FF")
[1] Example 8 of the Specification demonstrates the effect of in vivo
treatment of cartilage injury with SP. Specifically, cartilage injury
was surgically induced in rats after which some of the injured rats
were treated with SP (Spec. 52:1-51:2).
[2] Untreated rats were said to "not heal well in the initial two week
period" after injury, while SP-treated rats were said to show
"improved healing in the initial two week period" based on
combined criteria scores ranging from 0 (no damage) to 24
(indication of fibrosis and osteoarthritis): uninjured cartilage 1.8,
untreated cartilage defects 22.2, and SP-treated cartilage defects 11.9
(id. 51:5-52:2) (also see Figures 20A-20C).
[3] Example 9 of the Specification demonstrates the effect of in vitro
treatment of chondrocytes (cartilage cells). Specifically, CGRP,
NPY, SP, and VIP were added to chondrocyte cell cultures and the
amounts of cell proliferation and glycosaminoglycan ("GAG")
production measured vis-à-vis a control cell culture (not containing
added neuropeptide). (Spec. 52:12-53:8).
[4] Based on the measured data, the Specification states that "[t]hese
results unequivocally show that neuropeptides … increase the
proliferation of articular chondrocytes. Thus, the present invention
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is also useful to encourage the healing of damaged bone." (id. at
54:19-22). Further, according to the Specification, the GAG "results
corroborate the results of the cell proliferation assay. These results
further confirm that neuropeptides … increase the proliferation of
articular chondrocytes." (id. at 55:1-4) (also see Figures 21-23).
[5] The Examiner determined that "Appellant is enabled for improving
healing of a damaged cartilage or bone by administering CGRP, SP,
VIP or NPY to a subject having a damaged cartilage or bone" (Ans.
6).
[6] The 347 Application was filed May 10, 2006.
[7] Carticel is a one page document copyrighted 2005-2008 which
defines Carticel as
a biologic product using your own (autologous)
cultured cartilage cells (chondrocytes) to repair the
articular cartilage damage in your knee. These
cultured autologous cells are grown at Genzyme
Biosurgery, and then returned to your doctor and
put back into your knee during a procedure called
autologous chrondrocyte implantation (ACI).
(Carticel ¶ 1).

[8] According to a 2005 review article by Elefteriou,
[a]n increasing number of studies suggest that
nerve-derived signals play an important role in the
regulation of bone remodeling. Neuropeptides and
receptors/transporters of adrenergic, glutaminergic,
serotoninergic, dopaminergic and sensory nature
have been described in osteoblasts in vitro.
Downstream signaling pathways and target[] genes
have been identified, but the in vivo relevance of
these findings remained controversial until more
recent gene gain and loss of function studies
confirmed the role of CGRP and ß2-adrenergic
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receptor signaling in osteoblasts. …
[U]nderstanding how the central nervous system
integrates homeostatic signals with the regulation of
bone homeostasis will be the next exciting subject
of research in the field. (Elefteriou abstract,
emphasis added.)

[9] According to a 1998 article by Schaffer, "neuropeptides may affect
the proliferative and synthetic activity of … connective tissue cells"
(Schaffer 1107, col. 1, ¶ 1). "The peripheral nervous system (PNS),
acting through neuropeptides, … plays an effector role in the
inflammatory, proliferative, and reparative processes after injury" (id.
at 1107, col. 1, ¶ 2).
[10] Schaffer identifies SP, CGRP, VIP, NPY, and somatostatin as
important neuropeptides in Table 1 (id. at 1108). Table 1 reads:

[11] Schaffer focuses on the role of SP and CGRP in repair mechanisms
(id. at ¶ bridging 1107-1108).
[12] The Examiner relies on "p. 1109, 1st col, 2nd paragraph" of Schaffer
as teaching that "[i]t is known in the art that each neuropeptide has
its own unique biochemical properties and biological function" (Ans.
6).
[13] Page 1109, column 1, paragraph 2 (endnotes omitted), of Schaffer
reads
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Polymorphonuclear leukocytes (PMNs) are the first
inflammatory cells to enter the wound space from
the intact microcirculation at the edge of the wound,
peaking at 24 to 48 hours. Their main function
seems to be the phagocytosis of bacteria and
cellular debris to prevent wound infection. The
presence of PMNs does not seem to be essential for
normal healing of contaminated wounds.

C. Legal principles
"[T]o be enabling, the specification … must teach those skilled in the
art how to make and use the full scope of the claimed invention without
'undue experimentation.'" In re Wright, 999 F.2d 1557, 1561 (Fed. Cir.
1993). "When rejecting a claim under the enablement requirement of
section 112, the PTO bears an initial burden of setting forth a reasonable
explanation as to why it believes that the scope of protection provided by
that claim is not adequately enabled by the description of the invention
provided in the specification of the application …." Id. at 1561-1562. "That
some experimentation may be required is not fatal; the issue is whether the
amount of experimentation required is 'undue.'" In re Vaeck, 947 F.2d 488,
495 (Fed. Cir. 1991) (original emphasis).
Factors to be considered in determining whether a
disclosure would require undue experimentation …
include (1) the quantity of experimentation
necessary, (2) the amount of direction or guidance
presented, (3) the presence or absence of working
examples, (4) the nature of the invention, (5) the
state of the prior art, (6) the relative skill of those in
the art, (7) the predictability or unpredictability of
the art, and (8) the breadth of the claims.

In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). However, "it is not a
requirement of patentability that an inventor correctly set forth, or even
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know, how or why the invention works." Newman v. Quigg, 877 F.2d 1575,
1581 (Fed. Cir. 1989); see also Fromson v. Advance Offset Plate, Inc., 720
F.2d 1565, 1570 (Fed. Cir. 1983) ("[I]t is axiomatic that an inventor need not
comprehend the scientific principles on which the practical effectiveness of
his invention rests.").
D. Analysis
Here, the evidence of record weighs in favor of enablement.
According to the 1998 article by Schaffer, the peripheral nervous system
("PNS") was known to play an effector role in the inflammatory,
proliferative, and reparative processes after injury (FF 9). Since the PNS
was known to act through neuropeptides, the prior art suggested that
neuropeptides may affect the proliferative and synthetic activity of
connective tissue cells (FF 9). Schaffer identified five important
neuropeptides in Table 1 – SP, CGRP, VIP, NPY, and somatostatin – which
each acted on different types of nerve fibers and/or triggered different
peripheral nerve functions (FF 10). In the words of the Examiner, "each
neuropeptide [SP, CGRPY, VIP, NPY, and somatostatin] has its own unique
biochemical properties and biological function" (FF 12).
As the state of the art progressed, an increasing number of studies
suggested that nerve-derived signals, i.e., neuropeptides, played an important
role in the regulation of bone remodeling (FF 8). According to the 2005
review article by Elefteriou, the in vivo relevance of neuropeptide and
receptor/transporter signaling pathways discovered in osteoblasts (bone
precursor cells), "remained controversial until more recent … studies
confirmed the role of CGRP and ß2-adrenergic receptor signaling in
osteoblasts" (FF 8, emphasis added).
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The 347 Application was filed May 10, 2006 (FF 6). Example 9 of
the Specification was said to show that four of the five neuropeptides
identified in Table 1 of Schaffer, i.e., CGRP, NPY, SP, and VIP, promoted
cell proliferation of cultured chondrocytes in vitro (FF 3, 4, 10). Example 8
of the Specification was said to show that administration of SP improved the
healing of surgically induced cartilage damage in rats in vivo (FF 1-2).
Subsequently, the Examiner determined that the Specification enabled
"improving healing of a damaged cartilage or bone by administering CGRP,
SP, VIP or NPY to a subject having a damaged cartilage or bone" (FF 5).
Notably, as shown by Schaffer, CGRP, SP, VIP, and NPY are each different
neuropeptides has their own unique biochemical properties and biological
function (FF 10).
Thus, the evidence of record shows a progression from a general
suggestion of an idea that neuropeptides may affect the proliferative and
synthetic activity of connective tissue cells (Schaffer) to identification of
neuropeptide and receptor/transporter signaling pathways that "confirmed"
the role of at least one neuropeptide, i.e., CGRP, in bone repair (Elefteriou).
The instant Specification provides in vivo and in vitro data which the
Examiner has accepted as showing enablement for treatment by four of the
specifically recited neuropeptides, CGRP, SP, VIP, and NPY. The
Examiner asserts that the Specification is not enabling for the remaining
neuropeptide members of the defined Markush group recited in the claims
on appeal because "[t]he specification fails to teach the structural and
functional relationship among different neuropeptides and their cognate
receptors" (Ans. 14). However, the Specification is silent on the structural
and functional relationships between CGRP, SP, VIP, NPY, and their
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cognate receptors. Yet, according to Table 1 of Schaffer, the Examiner's
own relied-upon reference, these neuropeptides are known in the art to have
different structural and functional relationships from one another (FF 10).
Hence, the evidence of record weighs in favor of extrapolating the results
obtained with the neuropeptides CGRP, SP, VIP, and NPY to the other
neuropeptides of the Markush group recited in the method claims on appeal.
While it may well be that each of the neuropeptides recited in the method
claims treats damaged cartilage or bone via a different neuropeptide and
receptor/transporter signaling pathway, "it is axiomatic that an inventor need
not comprehend the scientific principles on which the practical effectiveness
of his invention rests." Fromson, 720 F.2d at 1570.
Finally, the Examiner's reliance on the function of polymorphonuclear
leukocytes in wound healing (FF 12-13) is not understood.
E. Conclusion
Therefore, we reverse the rejection of claims 1, 4-7, 9, and 10 under
§ 112, second paragraph. The evidence of record supports the determination
that treatment of damaged cartilage or bone with the neuropeptides CGRP,
SP, VIP and NPY is reasonably extrapolated to the rest of the neuropeptides
specifically recited in the Markush group of the method claims on appeal.
III. Anticipation
A. Introduction
The Examiner also rejected claims 7, 9, and 10 as unpatentable under
35 U.S.C. § 102(b) as anticipated by Delgado (Ans. 8-10). The Examiner
found that Delgado teaches treating rheumatoid arthritis ("RA"), a disease
characterized by chronic inflammation in the joints and destruction of bone
and cartilage, with VIP (id. at 9). The Examiner found that treatment of
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arthritis with VIP can improve the strength of the damaged cartilage or bone
and, therefore, the limitation of "improving the strength of a damaged
cartilage or bone" was inherent in the method of Delgado (id.).
Appellants argue that "[r]ather than describing treatment methods, …
Delgado … is given over to mechanistic studies regarding the cellular
mechanisms that give rise to collagen-induced arthritis in mice in the first
place" (App. Br. 11). Thus, according to Appellants, since Delgado is silent
on improving the strength of damaged cartilage or bone, the rejection over
Delgado is improper (id.).
At issue is whether there is a sufficient factual basis to find that
Delgado inherently describes improving the strength of a damaged cartilage
or bone in a subject suffering from said damage.
B. Additional findings of fact
[14] According to Delgado, rheumatoid arthritis ("RA") is "characterized
by chronic inflammation in the joints and subsequent destruction of
the cartilage and bone" (Delgado abstract).
[15] Delgado teaches that "administration of the neuropeptide vasoactive
intestinal peptide (VIP) … significantly reduced incidence and
severity of arthritis in an experimental model, completely abrogating
joint swelling and destruction of cartilage and bone" (id.).
[16] According to Delgado, "a single administration at the onset of
disease was enough to significantly ameliorate the pathologic signs
of arthritis" (id. at 563, col. 2, ¶ 3), i.e., "VIP can … ameliorate
already established disease" (id. at 563, col. 2, last full sentence).
[17] Further according to Delgado, "it has been reported that VIP inhibits
proliferation and production of IL-6, IL-8 and MMP-2 by fibroblast-
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like synovial cells from RA patients" (id. at 567, col. 1, last full
sentence).
[18] As explained by Delgado, "matrix metalloproteinases (MMPs) have
pivotal roles in the depletion of proteoglycan and collagen in the
joints, which leads to cartilage and bone erosion in RA patients" (id.
at 566, col. 1, ¶ 2).
C. Legal principles
It is well settled that when a claimed product or process reasonably
appears to be substantially the same as a product or process disclosed by the
prior art, the burden is properly upon the applicant to demonstrate that the
prior art product or process does not necessarily or inherently possess
characteristics attributed to the claimed product or process. In re Spada, 911
F.2d 705, 708 (Fed. Cir. 1990); In re Best, 562 F.2d 1252, 1255 (CCPA
1977). Objective evidence to the contrary is required to rebut the reasonable
presumption. Spada, 911 F.2d at 708; Best, 562 F.2d at 1255. Furthermore,
it is a general rule that "merely discovering and claiming a new benefit of an
old process cannot render the process again patentable." In re Woodruff, 919
F.2d 1575, 1578 (Fed. Cir. 1990).
D. Analysis
Claim 7 recites a method of improving the strength of a damaged
cartilage or bone by administering a neuropeptide, including VIP, to a
subject having damaged cartilage or bone in a cartilage or bone strength-
improving amount. Delgado administered VIP to a rat with chemically
induced RA, a disease characterized by destruction of the cartilage and bone,
and found that the VIP completely abrogated joint swelling and destruction
of cartilage and bone (FF 14-16). Thus, it reasonably appears that the
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claimed method is the same or substantially the same as the method of
Delgado and, therefore, it is proper to shift the burden to Appellants to show
that the method of Delgado does not necessarily or inherently possess the
claimed limitation of improving the strength of a damaged cartilage or bone.
Spada, 911 F.2d at 708; Best, 562 F.2d at 1255. This Appellants have not
done.
E. Conclusion
Therefore, we sustain the rejection of claims 7, 9, and 10 under
§ 102 as anticipated by Delgado. There is a sufficient factual basis to find
that Delgado inherently describes improving the strength of a damaged
cartilage or bone in a subject suffering from said damage.
IV. Order
Upon consideration of the record, and for the reasons given, it is
ORDERED that the decision of the Examiner to reject claims 1, 4-7, 9,
and 10 as unpatentable under 35 U.S.C. § 112, first paragraph, is
REVERSED;
FURTHER ORDERED that the decision of the Examiner to reject
claims 7, 9, and 10 as unpatentable under 35 U.S.C. § 102(b) as anticipated
by Delgado is AFFIRMED; and,
FURTHER ORDERED that 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)(iv).

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AFFIRMED-IN-PART

alw

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