Ex Parte Mantovani et al

Board of Patent Appeals and Interferences

Jun 2, 2010

10415413 (B.P.A.I. Jun. 2, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ALBERTO MANTOVANI, BARBARA BOTTAZZI,
GIUSEPPE PERI, and ANGELO MANFREDI
__________

Appeal 2010-000100
Application 10/415,413
Technology Center 1600
__________

Decided: June 2, 2010
__________

Before TONI R. SCHEINER, DEMETRA J. MILLS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
for preventing phagocytosis of apoptotic cells. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.

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Statement of the Case
Background
“The present invention relates to the use of the long pentraxin PTX3
(PTX3) or one of its functional derivatives for the preparation of a
medicament for the prevention and treatment of autoimmune diseases”
(Spec. 1, ll. 3-6).
The Claims
Claims 12-17 are on appeal. Claim 12 is representative and reads as
follows:
12. A method for preventing phagocytosis of apoptotic
cells comprising binding human long pentraxin (PTX3) or
mouse long pentraxin PTX3 to the apoptotic cells and
thereby prevent their phagocytosis by immature dendritic
cells.

The prior art
Botazzi et al. (Botazzi ‘516) WO 99/32516 Jul. 1, 1999
Botazzi et al, Pentraxins as a key component of innate immunity, 18
CURRENT OPINION IMMUNOL. 10-15 (2006).
Doni et al., Production of the soluble pattern recognition receptor
PTX3 by myeloid, but not plasmacytoid, dendritic cells, 33 EUR. J.
IMMUNOL. 2886-2893 (2003).
Garlanda et al., Non-redundant role of the long pentraxin PTX3 in
anti-fungal innate immune response, 420 NATURE 182-186 (2002).
Luchetti et al., Expression and production of long pentraxin PTX3 in
rheumatoid arthritis (RA), 119 CLIN. EXP. IMMUNOL. 196-202 (2000).
Napoleone et al., Long pentraxin PTX3 upregulates tissue factor
expression in human endothelial cells, 22 ARTERIOSCLER. THROMB. VASC.
BIOL. 782-787 (2002).
Rolph et al., Production of the long pentraxin PTX3 in advanced
atherosclerotic plaques, 22 ARTERIOSCLER. THROMB. VASC. BIOL. e10-e14
(2002).
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The issues
A. The Examiner rejected claims 12-17 under 35 U.S.C. § 112, first
paragraph as failing to comply with the enablement requirement (Ans. 3-8).
B. The Examiner rejected claims 12-17 under 35 U.S.C. § 102(b) as
anticipated by Botazzi ‘516 (Ans. 8).
C. The Examiner rejected claims 12-17 under 35 U.S.C. § 112, first
paragraph as failing to comply with the written description requirement by
adding New Matter (Ans. 8-10).
A. 35 U.S.C. § 112, first paragraph, Enablement
The Examiner finds that “in view of the Inventors’ subsequent
publications, whether or not the presence of PTX3 can block the
phagocytosis of apoptotic cells by immature DCs is at best unpredictable”
(Ans. 7). The Examiner concludes that the “specification provides
insufficient evidence that the administration of a long train pentraxin (PTX3)
would provide an effective treatment for a ‘patient suffering from
autoimmune diseases’” (Ans. 3-4).
Appellants argue that the “specific binding of PTX3 to apoptotic cells
is demonstrated by Example 1/1 which shows that PTX3 has the ability to
bind to cells undergoing apoptosis” (App. Br. 4). Appellants argue that “the
teachings and working examples in Appellants’ specification provide
sufficient guidance to predict that PTX3 binding to apoptotic cells would
enable prevention and treatment of an autoimmune disease” (App. Br. 6).

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In view of these conflicting positions, we frame the enablement issue
before us as follows:
Does the evidence of record support the Examiner’s conclusion that
undue experimentation would have been required to perform the method of
Claim 12?
Findings of Fact (FF)
Breadth of Claims
1. The preamble of Claim 12 states that the claim is a “method for
preventing phagocytosis of apoptotic cells” (Claim 12).
Presence of Working Examples
2. The Specification teaches in Example 2, that “that PTX3
acquired the ability to bind to cells undergoing later apoptosis and that
recognition by PTX3 does not depend on the initiating stimuli used to trigger
apoptosis. Moreover PTX3 lost the ability to bind to cells evolving toward a
postapoptotic phase” (Spec. 9, ll. 4-7).
Amount of Direction or Guidance Presented
3. The Specification teaches that “[t]o date a satisfactory cure for
most of the autoimmune diseases known does not exist” (Spec. 4, ll. 28-29).
4. The Specification teaches that the “binding between apoptotic
cells and PTX3 helps apoptotic cells clearance by macrophages, impeding
the phacocytosis [sic phagocytosis] of apoptotic cells by immature DCs
which promote autoimmune diseases” (Spec. 5, ll. 13-15).
State of the Prior Art and Unpredictability of the Art
5. Luchetti teaches that the “function of PTX-3 has not been
completely defined. . . . Therefore, it is tempting to speculate that in part
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PTX3 may amplify complement-mediated mechanisms responsible for
inflammation and tissue damage in RA [rheumatoid arthritis]” (Luchetti 201,
col. 1).
6. Garlanda teaches that “[o]ur results demonstrate that Ptx3 acts
as a soluble pattern-recognition receptor, which has a non-redundant role in
resistance against the fungal pathogen A. fumigatus” (Garlanda 184, col. 2).
7. Garlanda teaches that “Ptx3, unlike the short pentraxins made
in the liver, represents a mechanism of amplification of innate resistance
against pathogens mainly acting locally at sites of infection and
inflammation” (Garlanda 185, col. 1).
8. Botazzi ‘516 teaches that “[s]urprisingly, it has now been found
that the long pentraxin PTX3 or its functional derivatives are useful
therapeutic agents, particularly for the therapy of infectious and
inflammatory diseases or tumours” (Botazzi ‘516 5, ll. 4-7).
9. Doni teaches that “myeloid DC [dendritic cells] are a major
source of the prototypic long pentraxin PTX3, a soluble pattern recognition
receptor which facilitates interaction with pathogens and amplifies innate
immunity” (Doni 2887, col. 1).
10. Botazzi teaches that “in the presence of dying cells, PTX3
restricts the cross presentation of antigens derived from dying cells [ ].
These results suggest that PTX3 has a dual role: the protection against
pathogens and the control of auto-immunity” (Botazzi 12, col. 2).
Quantity of Experimentation
11. The Examiner makes no findings regarding the quantity of
experimentation required.
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Skill in the Art
12. The Examiner makes no findings regarding the skill level in the
art.
Principles of Law
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.

In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). “[T]he question of
undue experimentation is a matter of degree. The fact that some
experimentation is necessary does not preclude enablement; what is required
is that the amount of experimentation ‘must not be unduly extensive.”’ PPG
Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996).
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).

Analysis
The Examiner’s rejection is premised on the idea that “the prior and
post-filing art teaches that PTX3 is generally considered to be an
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immunostimulator or an immune response inducer” (Ans. 5). The Examiner
finds that the “use of such a stimulator or inducer in a patient in need of
immunosuppression to reduce an aberrant immune response (i.e., an
autoimmune patient) would generally be considered to be a poor approach to
treatment” (Ans. 5).
We are not persuaded by the Examiner’s rejection for several reasons.
First, the rejection is not consistent with the claims, which do not require any
treatment modality, much less treatment or cure of an autoimmune disease.
While Claim 13 has a “wherein” clause in which “phagocytosis of apoptotic
cells by immature dendritic cells increase the possibility of promoting an
autoimmune disease”, the wherein clause does not inform the mechanics of
how the “preventing” step is performed; rather, the wherein clause merely
characterizes the result of that step. Therefore, the wherein clause is not
entitled to weight in construing the claims. Cf. Minton v. National Assoc. of
Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003) (“The term
‘efficiently’ [in the whereby clause] on its face does not inform the
mechanics of how the trade is executed. . . . Rather, the term ‘efficiently’ is
a laudatory one characterizing the result of the executing step.”).1 Although

1 The claim interpreted in Minton read, in pertinent part:
“1. A method for trading securities between individuals,
comprising: . . . executing a trade of the security based on
information contained in the offer for consideration specified in
the reply to the offer, whereby the security is traded efficiently
between the first [offering] individual and the second [replying]
individual; . . . .” Minton, 336 F.3d at 1380 (emphasis in
original).

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the appealed claims use the word “wherein,” rather than the “whereby” used
in Minton’s claim, the introduced clauses merely characterize the result of
the method steps but do not inform the mechanics of the method.
Second, while there can be no reasonable dispute that the art shows a
role for PTX3 in protection against pathogens (FF 5-9), Botazzi directly
rebuts this narrow interpretation of the role of PTX3. Botazzi notes that
“PTX3 has a dual role: the protection against pathogens and the control of
auto-immunity” (Botazzi 12, col. 2). The Examiner has not explained why
PTX3 cannot have both roles, protection against pathogens while also
helping resist auto-immunity.
Consequently, as we balance the Wands factors, we find that the
Examiner has not established unpredictability in the use of PTX3 in
preventing phagocytosis of apoptotic cells, nor has the Examiner
demonstrated that that the working example, in concert with the teachings of
the Specification, would require undue experimentation to permit
performance of the claimed method.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that undue experimentation would have been required to perform the method
of Claim 12.

B. 35 U.S.C. § 102(b) over Botazzi ‘516
The Examiner finds that Botazzi ‘516
teaches a composition comprising human long train
pentraxin for the treatment of infectious and inflammatory
diseases, and tumors (see particularly Cla[i]ms 3 and 4). The
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treatment of a disease would necessitate the administration
of the composition and its binding to apoptotic cells in vivo
would then be an inherent property.

(Ans. 8).
Appellants argue that “there is no reasoning or evidence provided in
the final Office Action that gene therapy using PTX3 practiced in
accordance with WO 99/32516 would necessarily result in binding of PTX3
to apoptotic cells” (App. Br. 8).
In view of these conflicting positions, we frame the anticipation issue
before us as follows:
Does the evidence of record support the Examiner’s conclusion that
the method of treating infectious or inflammatory diseases or tumours would
inherently result in “binding human long pentraxin (PTX3) or mouse long
pentraxin PTX3 to the apoptotic cells and thereby prevent their phagocytosis
by immature dendritic cells” (Claim 12)?
Findings of Fact
13. Botazzi ‘516 teaches a “[c]omposition . . .in which the sequence
of the long pentraxin PTX3 is the sequence of human PTX3” (Botazzi ‘516
13, Claim 3).
14. Botazzi ‘516 teaches a “[c]omposition . . . for the treatment of
infectious and inflammatory diseases or tumours” (Botazzi ‘516 13, Claim
4).
15. Botazzi ‘516 teaches that mice “were subcutaneously injected
with 1x105 cells of P815 PTX3-producing clones or with clones containing
the antisense gene. The mice were monitored 3 times daily for occurrence
of tumours and once daily for survival” (Botazzi ‘516 9, ll. 15-19).
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16. Botazzi ‘516 teaches that the “results obtained . . . show the
efficacy of PTX3, in this experimental model of gene therapy, in bringing
about healing of the animals and complete rejection of the tumour after the
take of the inoculated tumour cells” (Botazzi ‘516 9, ll. 20-23).
17. The Specification teaches that “[c]ell death usually occurs in
vivo during the inflammatory process” (Spec. 2, l. 4).
18. The Specification teaches that “pro-inflammatory compounds
promote the apoptotic death of cells involved in the inflammatory process
and the physiological maturation of dendritic cells” (Spec. 2, ll. 1-2).
Principles of Law
“It is well settled that a prior art reference may anticipate when the
claim limitations not expressly found in that reference are nonetheless
inherent in it.” In re Cruciferous Sprout Litigation, 301 F.3d 1343, 1349
(Fed. Cir. 2002). See, e.g., MEHL/Biophile Int'l Corp. v. Milgraum, 192
F.3d 1362, 1365 (Fed.Cir.1999) (“Under the principles of inherency, if the
prior art necessarily functions in accordance with, or includes, the claimed
limitations, it anticipates.”)
Once a prima facie case of anticipation has been established, the
burden shifts to the Appellant to prove that the prior art product does not
necessarily or inherently possess the characteristics of the claimed product.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (“Where, as here, the claimed
and prior art products are identical or substantially identical, or are produced
by identical or substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily or inherently
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possess the characteristics of his claimed product.”). See also In re Spada,
911 F.2d 705, 708-09 (Fed. Cir. 1990).
Analysis
Botazzi ‘516 teaches administration of pentraxin (PTX3) to
individuals with inflammatory disorders and tumors (FF 13-14). Botazzi
‘516 exemplifies a treatment of tumors of mice with PTX3, demonstrating
that PTX3, but not the antisense of PTX3, results in tumor rejection (FF 15-
16). The Examiner relies upon the teachings in Appellants’ Specification
(see Ans. 8), which states that “[c]ell death usually occurs in vivo during the
inflammatory process” (Spec. 2, l. 4; FF 17). The Specification also teaches
that “pro-inflammatory compounds promote the apoptotic death of cells
involved in the inflammatory process and the physiological maturation of
dendritic cells” (Spec. 2, ll. 1-2; FF 18).
Appellants argue that “there is no reasoning or evidence provided in
the final Office Action that gene therapy using PTX3 practiced in
accordance with WO 99/32516 would necessarily result in binding of PTX3
to apoptotic cells” (App. Br. 8).
We are not persuaded. The teachings of the Specification, which
teach that apoptosis inherently occurs during inflammation, reasonably
support the Examiner’s finding that when Botazzi ‘516 treats inflammatory
disorders and tumors with PTX3, Botazzi ‘516 inherently and necessarily
results in binding of PTX3 to apoptotic cells present in the inflammatory
disorders. As the Examiner notes, “the skilled artisan would deliver the
gene into the location of the immune response, e.g., into a tumor or into a
lymph node, where apoptotic and immature DCs would be found” (Ans. 13).
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The Examiner has therefore provided significant evidence and
reasoning which support the conclusion that administration of PTX3 for
treatment of inflammatory disorders or tumors will result in binding of
PTX3 to apoptotic cells. Consequently, under Best, the burden of proving
that the administration of Botazzi ‘516 does not inherently satisfy the claims
is placed on Appellants. See In re Best, 562 F.2d 1252, 1255 (CCPA 1977)
(“Where, as here, the claimed and prior art products are identical or
substantially identical, or are produced by identical or substantially identical
processes, the PTO can require an applicant to prove that the prior art
products do not necessarily or inherently possess the characteristics of his
claimed product.”). Appellants have provided no evidence to rebut the
Examiner’s conclusion.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
method of treating infectious or inflammatory diseases or tumours would
inherently result in “binding human long pentraxin (PTX3) or mouse long
pentraxin PTX3 to the apoptotic cells and thereby prevent their phagocytosis
by immature dendritic cells” (Claim 12).
C. 35 U.S.C. § 112, first paragraph, New Matter
The Examiner finds that “[w]hile the claims no longer recite
administration of the PTX3, they still require that it be applied to some sort
of system (whether in vitro or in vivo) comprising apoptotic cells and
immature DCs. Said application is not supported by the instant
specification” (Ans. 9). The Examiner also finds that the Specification does
not provide support for “a method wherein phagocytosis of apoptotic cells
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by immature dendritic cells increase the possibility of promoting an
autoimmune disease” (App. Br. 10).
Appellants argue that the “specification clearly describes PTX3 as a
useful therapeutic agent capable of inhibiting the recognition of self antigens
as foreign and alleviating symptoms of autoimmune diseases. Thus, the use
of PTX3 for preventing phagocytosis of apoptotic cells is fully supported by
the disclosure as originally filed” (App. Br. 10). Appellants argue that the
“skilled person would appreciate that in the context of Appellants’ claimed
invention the terms ‘promote’ (see page 7, line 23) and ‘start’ (page 7, line
19) have the same meaning as the term ‘onset’ (page 5, line 20) according to
the specification and what was known in the art” (App. Br. 11).
In view of these conflicting positions, we frame the written
description issue before us as follows:
Does the evidence of record support the Examiner’s finding that the
Specification does not provide descriptive support for application of PTX3
to apoptotic cells where “phagocytosis of apoptotic cells by immature
dendritic cells increase the possibility of promoting an autoimmune disease”
(Claim 13)?
Findings of Fact
19. The Specification teaches that “during inflammation and
increased cellular death the huge amount of death cells blocks the capacity
of the organism to remove such cells, these cells accumulate into the tissues
and are available for phagocytosis by non-conventional phagocytes such as
immature DCs cells, with an increase of the possibility that the autoimmune
process starts” (Spec. 5, ll. 8-12).
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20. The Specification teaches that the “binding between apoptotic
cells and PTX3 helps apoptotic cells clearance by macrophages, impeding
the phacocytosis [sic phagocytosis] of apoptotic cells by immature DCs
which promote autoimmune diseases” (Spec. 5, ll. 13-15).
Principles of Law
[T]he hallmark of written description is disclosure. . . . the
test requires an objective inquiry into the four corners of the
specification from the perspective of a person of ordinary
skill in the art. Based on that inquiry, the specification must
describe an invention understandable to that skilled artisan
and show that the inventor actually invented the invention
claimed.

Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010).
“[T]he written description requirement does not demand either
examples or an actual reduction to practice; a constructive reduction to
practice that in a definite way identifies the claimed invention can satisfy the
written description requirement” id.
It is the Examiner's “initial burden [to] present [ ] evidence or reasons
why persons skilled in the art would not recognize in the disclosure a
description of the invention defined by the claims.” In re Wertheim, 541
F.2d 257, 263 (CCPA 1976).
Analysis
The Examiner finds that “[w]hile the claims no longer recite
administration of the PTX3, they still require that it be applied to some sort
of system (whether in vitro or in vivo) comprising apoptotic cells and
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immature DCs. Said application is not supported by the instant
specification” (Ans. 9).
We are not persuaded by the Examiner’s rejection. The Specification
clearly teaches that “binding between apoptotic cells and PTX3 helps
apoptotic cells clearance by macrophages, impeding the phacocytosis [sic
phagocytosis] of apoptotic cells by immature DCs which promote
autoimmune diseases” (Spec. 5, ll. 13-15; FF 20). This is an express
teaching of the limitation argued by the Examiner.
The Examiner also finds that the Specification does not provide
support for a method wherein ‘“phagocytosis of apoptotic cells by immature
dendritic cells increase the possibility of promoting an autoimmune
disease”’ (App. Br. 10).
We are not persuaded. The Specification teaches that “during
inflammation and increased cellular death the huge amount of death cells
blocks the capacity of the organism to remove such cells, these cells
accumulate into the tissues and are available for phagocytosis by non-
conventional phagocytes such as immature DCs cells, with an increase of the
possibility that the autoimmune process starts” (Spec. 5, ll. 8-12; FF 19).
This is an express teaching which connects phagocytosis by immature
dendritic cells with an autoimmune process.
The Examiner’s argument that there is a distinction between “start”
and “promoting” is not persuasive. In the context of Claim 13 and the
Specification, both terms clearly refer to the initiation of the onset of an
autoimmune disease, by presentation of “self” antigens by dendritic cells
followed by activation of the immune system against these “self” antigens.
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Both Claim 13 and the Specification are concerned with preventing such
presentation by preventing the initial phagocytosis of the “self” antigens by
the immature dendritic cells (FF 19-20, Claims 12-13).
Conclusion of Law
The evidence of record does not support the Examiner’s finding that
the Specification does not provide descriptive support for application of
PTX3 to apoptotic cells where “phagocytosis of apoptotic cells by immature
dendritic cells increase the possibility of promoting an autoimmune disease”
(Claim 13).
SUMMARY
In summary, we affirm the rejection of claim 12 under 35 U.S.C. §
102(b) over Botazzi ‘516. Pursuant to 37 C.F.R. § 41.37(c)(1)(vii)(2006),
we also affirm the rejection of claims 13-17 as these claims were not argued
separately.
We reverse the rejection of claims 12-17 under under 35 U.S.C. § 112,
first paragraph as failing to comply with the enablement requirement.
We reverse the rejection of claims 12-17 under 35 U.S.C. § 112, first
paragraph as failing to comply with the written description requirement by
adding New Matter.

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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)(2006).

AFFIRMED

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