Ex Parte Latta

Board of Patent Appeals and Interferences

Oct 10, 2007

10660924 (B.P.A.I. Oct. 10, 2007)

The opinion in support of the decision being entered today
is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte PAUL P. LATTA
__________

Appeal 2007-1152
Application 10/660,924
Technology Center 1600
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Decided: October 10, 2007
__________

Before ERIC GRIMES, LORA M. GREEN, and RICHARD M.
LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal from the Examiner’s final rejection of
claims 2-9. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

STATEMENT OF THE CASE
The Specification describes methods of creating immunological
tolerance to cells and tissues comprising implanting in the mammal a
tolerizing dose of cells or tissue encapsulated in a biologically compatible
permselective membrane (Spec. 3). The Specification states that this
Appeal 2007-1152
Application 10/660,924

process can be used to prevent certain diseases, such as Type I diabetes
(Spec. 10: 12-17).
Claims 2-9 are pending and appealed (Supp. Appeal Br.1 2). Claims
2-9 stand rejected under 35 U.S.C. § 112, first paragraph, as lacking
enablement (Answer 4) and also for lacking written description (Answer 8).
We select claim 2, the only independent claim on appeal, as
representative of the claims. It reads as follows:
2. A method of preventing onset of Type I diabetes in a
mammal predisposed to Type I diabetes, comprising implanting
a dose of insulin-producing cells encapsulated in a biologically-
compatible membrane into an implantation site in said mammal
prior to onset of Type I diabetes, wherein said dose is at least
one order of magnitude less than that necessary to achieve
normoglycemia in a mammal of the same species.

DISCUSSION
Enablement rejection
“To be enabling, the specification of a patent must teach those skilled
in the art how to make and use the full scope of the claimed invention
without ‘undue experimentation.’” Genentech, Inc. v. Novo Nordisk, A/S,
108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997) (quoting In
re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (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

1 “Supp. Appeal Br.” is a reference to the Supplemental Appeal Brief which
is date stamped Jul. 19, 2006.
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specification of the application; this includes, of course, providing sufficient
reasons for doubting any assertions in the specification as to the scope of
enablement. . . . Marzocchi, 439 F.2d at 223-24, 169 USPQ at 369-70.” In
re Wright, 999 F.2d at 1561-62, 27 USPQ2d at 1513 (Fed. Cir. 1993).
Enablement is determined as of the application filing date. See In re
Brana, 51 F.3d 1560, 1567 n.19, 34 USPQ2d 1436, 1441 n.19 (Fed. Cir.
1995). Thus, the issue in this rejection is whether the Examiner has set forth
a reasonable explanation as to why the scope of protection provided by the
claims is not adequately enabled by the Specification as of the application
filing date.
The Examiner contends that the Specification does not adequately
teach how to effectively prevent the onset of Type I diabetes in any mammal
predisposed to it (Answer 4). The Examiner asserts that the Specification
“only discloses the effects of the implanting of insulin-producing cells on the
level of blood glucose using streptozotocin-induced [diabetes] in murine
experimental model, using NOD mouse. (See Examples 1-2 in particular)”
(Answer 4). However, the Examiner contends that the examples are
insufficient to enable the scope of the claims because “the state of the art is
that it is unpredictable [from] the in vivo murine data using NOD model
disclosed in the specification as [to] whether the instant invention can be
used for the in vivo preventing onset of type I diabetes in mammals
including human” (Answer 7). To support the position that the murine
model is not adequate to predict the efficacy of the method as it is broadly
claimed, the Examiner cites six literature references: Atkinson (Nature,
1999, vol. 5, pages 601-604), Knip (Acta Paediatr. Suppl., 1998, vol. 452,
pages 54-62), Metas (J. of Immunology, 2004, vol. 172, pages 2731-2738),
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Tufveson (Immun. Reviews, 1993, No. 136, pages 101-107), Feldman
(Transplant. Proc., 1998, vol. 30, pages 4126-4127), and Cochlovius
(Modern Drug Discovery, October 2003, pages 33-38), and discusses their
relevance to the enablement issue (Answer 4-7).
We have considered the Examiner’s arguments and the supporting
documents, but do not find that the evidence is sufficient to sustain the
rejection.
In beginning our analysis, we note that the Examiner did not correctly
characterize the disclosure in the Specification. Example 1 describes the
treatment of streptozotocin-induced diabetes in C57B6 mice (Spec. 19: 30 to
20: 3), not NOD mice as stated on page 4 of the Answer. The Specification
provides experimental evidence in this example that a tolerizing first dose of
encapsulated insulin-producing cells induced immunological tolerance to a
subsequent curative dose of cells.
Turning to the references cited by the Examiner in support of his
position, we first address Mestas (supra.). The Examiner states that Mestas
provides evidence of the inadequacy of mouse models in predicting the
efficacy of therapies for human disease (Answer 5). Mestas – as noted by
the Examiner – describes the differences between mouse and human
immunology, concluding that “[s]uch differences should be taken into
account when using mice as preclinical models of human disease” (Mestas,
Abstract). Mestas describes its purpose as “to understand the potential
limitations of extrapolating data from mice to humans” (Mestas, at 2731,
col. 2). After extensively characterizing the immunological differences,
Mestas concludes:
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While caution in interpreting preclinical data obtained in mice
is clearly warranted, we believe that with these caveats in mind,
mice will continue to be the premiere in vivo model for human
immunology and will be absolutely essential for continued
progress in our understanding of immune function in health and
disease.
(Mestas, at 2736, col. 2.) Thus, far from abandoning the mouse as a model
of human disease, Mestas characterizes it as “absolutely essential for
continued progress” in understanding immunological diseases.
The Examiner contends that Tufveson’s statement that “today’s small
animal models seem to be insufficient to produce data for clinical decision-
making” (Tufveson, at 101) raises reasonable doubt about the predictability
of mouse models (Answer 6). However, Tufveson concluded that after “this
airing of problems in the clinical field it is clear that small animal models are
sought” for human disease (Tufveson, at 101). Tufveson reviewed its own
efforts at developing such models and concludes that “it would seem to be
reasonable to test new immunosuppressive drugs . . . in allograft models”
(Tufveson, at 107). Thus, Tufveson does not disavow the use of animal
models nor does it provide any evidence that the particular mouse model
described in the Specification is deficient.
With respect to the NOD mouse model of Type I diabetes, Atkinson
acknowledges that “specific differences . . . restrict their interpretation”
(Atkinson, at 601, col. 2), but also states that “investigations of NOD mice
have enhanced our appreciation of the etiologic complexity of type I
diabetes in humans and provided an example of how promising results
obtained in an animal model can be translated into human clinical trials”
(Atkinson, at 604, col. 1). Thus, contrary to the Examiner’s position,
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Atkinson recognizes that NOD mice – despite species differences – have
value in predicting outcome in human disease.
Appellant provided two declarations by Dr. David Scharp
(“Declaration of David Scharp, M.D.”, dated Nov. 25, 2003, and “Second
Declaration of David Scharp, M.D. under 37 C.F.R. § 1.132”, dated Apr. 28,
2005) showing that NOD mice who received the treatment described in the
Specification were prevented from becoming diabetic (Supp. Appeal Br. 5-6;
Declaration of David Scharp, M.D., ¶ 5-8). For example, Scharp showed
that 3 out 10 mice who received the tolerizing dose of encapsulated islet
cells, prior to the onset of diabetes, remained diabetes-free after eight weeks
(Declaration of David Scharp, M.D., ¶ 10). Atkinson states that NOD mouse
are the favored model for Type I diabetes (Atkinson, at 601, col. 1), and as
discussed above, considered them an important tool for understanding and
developing treatments for diabetes (Atkinson, at 604, col. 1).2 Thus, we find
the post-filing evidence in the Scharp Declarations sufficient “to prove that
the disclosure was in fact enabling when filed.” In re Brana, 51 F.3d 1560,
1576, fn.19, 34 USPQ2d 1436, fn.19 (Fed. Cir. 1995).
The Examiner’s position appears to be that because mouse models
don’t always work,3 they cannot be relied upon to enable a specification –

2 Dr. Scharp makes similar comments about the value of NOD mice,
including their proven value in developing markers for predicting human
patients who will develop clinical Type I diabetes (Second Declaration of
David Scharp, M.D. under 37 C.F.R. § 1.132, ¶ 2).
3 “Mestas . . . teach that there exist significant differences between mice and
humans in immune system development . . . [quoting Mestas:] [‘]As
therapies for human diseases become ever more sophisticated and
specifically targeted[,] it becomes increasing important to understand the
potential limitations of extrapolating data from mice to humans. The
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there being always a degree of uncertainty about whether the treatment will
prove to be effective in humans. In our opinion, this is not a reasonable
standard by which to measure enablement.
The publications cited by the Examiner acknowledge that there are
weaknesses in available mouse models as surrogates for human disease, but
these same publications continue to use the animal models to study human
disease because the animal models are apparently “‘as good as it gets’, short
of a study in humans” (Atkinson, at 601).
In cases where the utility of claimed compounds were questioned, the
Federal Circuit has repeatedly held that in vitro and animal tests, when
reasonably correlated with the in vivo activity asserted as the utility, were
sufficient to satisfy the utility requirement of 35 U.S.C. § 101. Cross v.
Iizuka, 753 F.2d 1040, 1051, 224 USPQ 739, 747 (Fed. Cir. 1985). In In re
Brana, 51 F.3d 1560, 34 USPQ2d 1436 (Fed. Cir. 1995), the PTO had
argued that mouse data was insufficient to establish utility for a cancer
treatment drug. In rejecting this position, the Federal Circuit wrote:
The Commissioner counters that such in vivo tests in animals
are only preclinical tests to determine whether a compound is
suitable for processing in the second stage of testing, by which
he apparently means in vivo testing in humans, and therefore
are not reasonably predictive of the success of the claimed
compounds for treating cancer in humans. The Commissioner,
as did the Board, confuses the requirements under the law for
obtaining a patent with the requirements for obtaining
government approval to market a particular drug for human
consumption. See Scott v. Finney, 34 F.3d 1058, 1063, 32
literature is littered with the examples of therapies that work well in mice
but fail to provide similar efficacy in humans[’] [Mestas, at 271] (emphasis
added)” (Answer 5).
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USPQ2d 1115, 1120 (Fed. Cir. 1994) (“Testing for the full
safety and effectiveness of a prosthetic device is more properly
left to the Food and Drug Administration (FDA). Title 35 does
not demand that such human testing occur within the confines
of Patent and Trademark Office (PTO) proceedings.”).
(Brana, at 1567, 34 USPQ2d at1442.) We see no reason why enablement of
a method claim whose scope includes humans should likewise require
human testing. Thus, in view of Brana, we conclude that animal models can
be used to establish enablement under § 112, first paragraph of a method
claim.
The relevant standard is rather whether the scope of the claims bears
“a reasonable correlation to the scope of enablement provided by the
specification to persons of ordinary skill in the art.” In re Fisher, 427 F.2d
833, 839, 166 USPQ 18, 24 (CCPA 1970). See also Invitrogen Corp. v.
Clontech Laboratories Inc., 429 F.3d 1052, 1071, 77 USPQ2d 1161, 1173-
1174 (Fed. Cir. 2005). In this case where an animal model serves as the
enablement for the claimed method, the proper question is whether it
reasonably correlates with the method for which patent protection is sought.
On this point, the Examiner has provided no evidence that results obtained
with streptozotocin-induced diabetes in C57B6 mice, as described in the
Specification, do not reasonably correlate with the scope of claim 2.
In contrast, Appellant has provided post-filing evidence, that together with
Atkinson’s teaching about the acceptability of NOD mouse as a model for
diabetes, establishes by the preponderance of the evidence that the
Specification as filed is, in fact, enabling. See In re Oetiker, 977 F.2d 1443,
1445, 24 USPQ2d 1443, 1444 (Fed. Cir. 1992) (“[P]atentability is
determined on the totality of the record, by a preponderance of the
evidence.”).
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The Examiner has provided no other explanation as to why the claim
is not adequately enabled for the claimed method of preventing onset of
Type I diabetes. Thus, on the record before us, we conclude that the
Examiner has not sustained the burden of establishing a reasonable basis to
question the scope of enablement of the claimed invention. We reverse the
rejection of claims 2-9 for lack of enablement

Written description rejection
Under 35 U.S.C. § 112, first paragraph, the specification must contain
a written description of the invention. Thus, when claims are amended
during patent prosecution, the claimed invention, in its amended form, must
be described in the specification. “An applicant complies with the written
description requirement ‘by describing the invention, with all its claimed
limitations.’ Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41
USPQ2d 1961, 1966 (1997).” Gentry Gallery v. The Berkline Corp., 134
F.3d 1473, 1479, 45 USPQ2d 1498, 1502-1503 (Fed. Cir. 1998).
The Examiner contends that claims 2-9, which were added by an
amendment dated April 1, 2004, are not described in the Specification as it
was originally filed (Answer 8). The Examiner argues that the Specification
“as originally filed only disclosed [a] two-step process” involving tolerizing
and curative doses (Answer 12), not a one-step method of “preventing type I
diabetes comprising … implanting a tolerizing dose of insulin-secreting
cells” in which the dose is at least one order of magnitude less than a
curative dose (Answer 12). We do not agree.
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The Specification in its original disclosure describes a one-step
process of administering a tolerizing dose of insulin-secreting cells. In the
“Summary of the Invention,” it is stated:
One embodiment of the invention is a method of creating
immunological tolerance to foreign cells, tissues or organs in a
mammal, comprising the step of implanting in the mammal a
tolerizing dose of foreign cells or tissue encapsulated in a
biologically compatible permselective membrane. The method
may additionally comprise the step of administering to the
mammal a curative dose.
(Spec. 3-4.)
An original claim of the Specification also describes a single step
method:
1. A method of creating immunological tolerance to foreign
cells, tissues or organs in a mammal, comprising the step of
implanting in said mammal a tolerizing dose of corresponding
foreign cells or tissue which shed antigens contained in or on
said foreign cells [,] tissues or organs, said corresponding
foreign cells or tissue being encapsulated in a biologically-
compatible permselective membrane.
(Spec. 27.)
The tolerizing dose is characterized in the original Specification as
being “one to two orders of magnitude less than the curative dose” (Spec. 4:
26-27) and “one or two orders of magnitude less than a full dose implant”
(Spec. 12: 26-27). It is stated in the Specification that the “amount of cells
. . . necessary for the initial tolerizing implant will vary” (Spec. 12: 24-25)
and “the size of these doses . . . can be optimized” (Spec 12: 30-31). Thus,
the Specification describes a dose of one order of magnitude less than a
curative dose (i.e., the dose recited in clam 2 which is “necessary to achieve
normoglycemia in a mammal of the same species”) and that this amount
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could be routinely varied. Thus, we conclude that the limitation “wherein
said dose is at least one order of magnitude less than that necessary to
achieve normoglycemia in a mammal of the same species” is supported by
the originally filed Specification.
The Specification also explicitly describes preventing diabetes using a
single dose of cells – the method of instant claim 2:
The process of the invention can also be used to prevent certain
diseases, particularly autoimmune disorders. In these cases the
process is as follows. First, patients at high risk for the disease
or already in the very early phase of the disease are identified.
At the critical time of the onset, the process is intervened with
the small encapsulated tissue. For example, islets are used for
Type I diabetes and collagen is used for arthritis. This implant
of foreign tissue immediately diverts the attention of the
immune system to the new foreign invader and it begins the
process to destroy this new threat. Because of this diversion,
the process of self-destruction of desirable tissue that was just
beginning is suppressed, then abandoned, then forgotten. It is,
in essence, “switched off” and the damage is prevented.
(Spec. 10: 12-21.) It is also stated that implants for prevention of disease
can be in tolerizing amounts (Spec 19: 1-15).
In sum, we find that all the limitations of claim 2 are described in the
originally filed Specification. Accordingly, the rejection of claims 2-9 as
lacking written description is reversed.

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CONCLUSION
The rejection of claims 2-9 under 35 U.S.C. § 112, first paragraph, as
lacking enablement and written description are

REVERSED.

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