Ex Parte Waldmann et al

Board of Patent Appeals and Interferences

Jul 6, 2011

10615718 (B.P.A.I. Jul. 6, 2011)

UNITED STATES PATENT AND TRADEMARKOFFICE
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.
10/615,718 07/09/2003 Herman Waldmann 695458-79 9454
7590 07/06/2011
CARELLA, BYRNE, BAIN, GILFILLAN, CECCHI,
STEWART & OLSTEIN
6 Becker Farm Road
Roseland, NJ 07068
EXAMINER
BLANCHARD, DAVID J
ART UNIT PAPER NUMBER
1619
MAIL DATE DELIVERY MODE
07/06/2011 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte HERMAN WALDMANN,
MARK RAYMOND FREWIN,
LISA KIM GILLILAND, and
LUIS RICARDO SIMOES DA SILVA GRACA
__________

Appeal 2011-003005
Application 10/615,718
Technology Center 1600
__________

Decided:
__________

Before DONALD E. ADAMS, LORA M. GREEN, 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 a
therapeutic antibody composition. We have jurisdiction under 35 U.S.C.
§ 6(b). We affirm.

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Statement of the Case
The Claims
Claims 1, 6-10, 12-15, and 17 are on appeal. Claim 1 is representative
and reads as follows:
1. A pharmaceutical comprising:
(a) a therapeutic antibody that binds to a therapeutic
target, said antibody being modified with a peptide that
reduces binding of the antibody to the therapeutic target,
said modified antibody being effective for reducing side
effects caused by the antibody and for producing a
therapeutic effect by binding to the therapeutic target,
wherein said antibody includes an antibody combining site
that binds to the therapeutic target, and said peptide is bound
to the antibody combining site of said antibody; and
(b) a pharmaceutical carrier.

The issues
A. The Examiner rejected claims 1, 6, 9, 10, and 17 under 35 U.S.C. §
102(b) as anticipated by Hale1 (Ans. 3-4).
B. The Examiner rejected claims 1, 6-10, 12-15, and 17 under 35 U.S.C.
§ 112, first paragraph as failing to satisfy the written description requirement
(Ans. 6-9).
C. The Examiner rejected claims 1, 6-10, 12-15, and 17 under 35 U.S.C.
§ 112, first paragraph as not enabling for all therapeutic antibodies modified
by any peptide wherein the therapeutic antibody has reduced side effects and
produces a therapeutic effect (Ans. 11-14).

1 Hale, G., Synthetic peptide mimotope of the CAMPATH-1 (CD52)
antigen, a small glycosylphosphatidylinositol-anchored
glycoprotein, 1 IMMUNOTECHNOLOGY 175-187 (1995).
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A. 35 U.S.C. § 102(b) over Hale
The Examiner finds that Hale teaches “an anti-CD52 humanized
antibody, CAMPATH-1H, reversibly bound by the synthetic peptide,
QTSSPSAD, a CD52 mimotope that inhibits binding of CAMPATH-lH to
human lymphocytes expressing CD52 by about four fold and the antibody is
disclosed in various buffers including PBS, which are reasonably interpreted
to be a ‘pharmaceutically acceptable carrier’” (Ans. 3).
Appellants contend that “Hale, however, does not disclose or even
remotely suggest to one of ordinary skill in the art that the Campath antibody
may be modified with such mimotopes in order to provide a modified
antibody” (App. Br. 4). Appellants contend that in “contrast to Hale,
Applicants modify an antibody with a peptide in order to inhibit binding of
the antibody to a therapeutic target, and to reduce the immune response
against the antibody” (App. Br. 5).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Hale anticipates claim 1?
Findings of Fact (FF)
1. The Specification teaches that in one “embodiment there is
provided a therapeutic antibody that is modified to include a compound that
is reversibly bound to the antibody combining site of the antibody, with the
target antigen competing with the compound for binding to the ACS upon
administration of the antibody, or the binding of the antigen otherwise being
inhibited by the compound, whereby binding of the antibody to the target is
inhibited” (Spec. 2, ll. 16-21).
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2. Hale teaches that “[r]eal time binding analysis of CAMPATH-1
antibodies to a synthetic peptide was carried out using a BIAcore
(Pharmacia). The peptide-carrier conjugate (QTSSPSADA-bovine serum
albumin) was coupled to a sensor chip” (Hale 178, col. 1).
3. Hale teaches that “[h]uman peripheral blood mononuclear cells
were incubated with serial dilutions of CAMPATH·1H in the presence of
either diluent alone, or the BSA conjugates of either the minimal surrogate
antigen (TSSPSAD) or an irrelevant peptide (TKKTPLK) derived from the
putative mouse CD 52 homologue” (Hale 183, col. 2).
4. Hale teaches that the “minimal surrogate antigen coupled to
BSA (1 mg/ml) reduced the binding titre of CAMPATH·1H by about four
fold, indicating a modest ability to compete” (Hale 183, col. 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
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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.”). See also In re Spada,
911 F.2d 705, 708-09 (Fed. Cir. 1990).
Analysis
Hale satisfies all of the structural requirements of claim 1, as
reasonably interpreted in light of Appellants’ Specification (FF 1). It is
undisputed that Hale teaches a therapeutic antibody, a pharmaceutical carrier
and a peptide which reduces binding of the antibody to a target (FF 2-4).
Appellants contend that “Hale, however, does not disclose or even
remotely suggest to one of ordinary skill in the art that the Campath antibody
may be modified with such mimotopes in order to provide a modified
antibody” (App. Br. 4). Appellants contend that in “contrast to Hale,
Applicants modify an antibody with a peptide in order to inhibit binding of
the antibody to a therapeutic target, and to reduce the immune response
against the antibody” (App. Br. 5).
We are not persuaded. Appellants’ Specification clearly indicates that
“modification” may include “a compound that is reversibly bound to the
antibody combining site of the antibody” (Spec. 2, ll. 17-18; FF 1).
Therefore, claim 1 is reasonably interpreted as encompassing the antigen of
Hale, which is taught to reversibly bind and compete for binding with the
CAMPATH antibody (FF 2-4).
The Examiner has provided substantial evidence and reasoning which
support the conclusion that the CAMPATH antibody, antigen and carrier
satisfy the requirements of claim 1. Consequently, under Best, the burden of
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proving that Hale’s composition does not inherently satisfy the functional
requirements of claim 1 is properly 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 Hale
anticipates claim 1.
B. 35 U.S.C. § 112, first paragraph, written description
The Examiner finds that “the claims are drawn to a broad genus of
pharmaceutical compositions comprising a therapeutic antibody being
modified with a peptide that is effective for reducing side effects caused by
the antibody and wherein the therapeutic antibody produces a therapeutic
effect by binding to the therapeutic target” (Ans. 6). The Examiner finds
that “[h]owever, the written description in this case only sets forth one
therapeutic antibody, humanized anti-CD52 antibody (CAMPATH-1H),
which is modified by linking the antibody to the CD52 mimotope
TSSPSAD or the CD52 mimotope mutant QTSAAA VD and which reduces
cytokine release (i.e., reduced side effect)” (Ans. 6).
Appellants contend that the “specification describes what the
invention is as well as what the invention does. The present invention is
directed to a pharmaceutical that comprises a therapeutic antibody that
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includes an antibody combining site, and is modified with a peptide that is
bound to the antibody combining site” (App. Br. 5-6). Appellant also argues
that “[t]hose skilled in the art understand readily that different antibodies
will have different antibody combining sites, and that the location of the
antibody combining site of an antibody can be determined by routine
experimentation” (App. Br. 6).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the disclosure of the Specification
failed to demonstrate possession and descriptive support for Claim 1?
Findings of Fact
5. The Specification teaches a single example with four constructs,
showing “the binding abilities of the various antibody constructs to CD52-
bearing HUT cells. CP-IH Wild Type has a binding efficiency
approximately 5 times greater than binding of CP-IH Linker alone,
approximately 100 times greater than CP-MlMmut9, and approximately
10,000 times greater than CP-CD52MIM” (Spec. 17, ll. 5-9).
Principles of Law
[T]he hallmark of written description is disclosure.… [T]he
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).

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Analysis
We agree with the Examiner that the Specification does not
adequately describe the pharmaceutical composed of a therapeutic antibody,
modifying peptide, and carrier as broadly claimed.
It is well settled that:
the inventor cannot lay claim to that subject matter unless he
can provide a description of the compound sufficient to
distinguish infringing compounds from non-infringing
compounds, or infringing methods from non-infringing
methods. As the district court observed, “[t]he claimed
method depends upon finding a compound that selectively
inhibits PGHS-2 activity. Without such a compound, it is
impossible to practice the claimed method of treatment.”

University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir.
2004).
Claim 1, as interpreted in light of the Specification, is broadly drawn
to any composition of an antibody and peptide, where the peptide reduces
the binding of the antibody to its therapeutic target. The Specification
therefore must adequately describe that genus of compounds.
The written description requirement can be met by disclosing
“complete or partial structure, other physical and/or chemical properties,
functional characteristics when coupled with a known or disclosed
correlation between function and structure, or some combination of such
characteristics.” Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964,
(Fed. Cir. 2002).
In this case, the Specification has a single working example of a
Campath antibody and peptide (see FF 5). However, the Specification does
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not describe any of the specific structural features, physical or chemical
properties, or other information which would permit identification of
antibody/peptide combinations which would satisfy the requirements of the
claim. The claim is entirely functional.
The present case is therefore analogous to Rochester and Ariad. In
Rochester, the patent claimed a method of selectively inhibiting the enzyme
PGHS-2 (also known as COX-2) by “administering a non-steroidal
compound that selectively inhibits activity of the PGHS-2 gene product to a
human.” Rochester, 358 F.3d at 918. The patent “describes in detail how to
make cells that express either COX-1 or COX-2, but not both …, as well as
‘assays for screening compounds, including peptides, polynucleotides, and
small organic molecules to identify those that inhibit the expression or
activity of the PGHS-2 gene product.”’ Rochester, 358 F.3d at 927.
The court held that even if a DNA sequence might support a claim to
hybridizing nucleic acids, the “same is not necessarily true in the chemical
arts more generally. Even with the three-dimensional structures of enzymes
such as COX-1 and COX-2 in hand, it may even now not be within the
ordinary skill in the art to predict what compounds might bind to and inhibit
them.” Rochester, 358 F.3d at 925.
The concern is even more acute in the current case, where unlike in
Rochester, where the claims involved only the use of the natural COX-2
molecule, here the claims encompass any therapeutic antibody and any
peptide whatsoever.
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As in Rochester, the present application discloses an exemplary
situation, but does not provide any further information on such therapeutic
antibodies and peptide partial inhibitors.
As the district court pointed out: Tellingly, … what
plaintiff’s experts’ [sic] do not say is that one of skill in the
art would, from reading the patent, understand what
compound or compounds-which, as the patent makes clear,
are necessary to practice the claimed method-would be
suitable, nor would one know how to find such a compound
except through trial and error …. Plaintiff’s experts opine
that a person of ordinary skill in the art would understand
from reading the ‘850 patent what method is claimed, but it
is clear from reading the patent that one critical aspect of the
method-a compound that selectively inhibits PGHS-2
activity-was hypothetical, for it is clear that the inventors
had neither possession nor knowledge of such a compound.

Rochester, 358 F.3d at 925-926.
Appellants contend that the “specification describes what the
invention is as well as what the invention does. The present invention is
directed to a pharmaceutical that comprises a therapeutic antibody that
includes an antibody combining site, and is modified with a peptide that is
bound to the antibody combining site” (App. Br. 5-6). Appellant also argues
that “[t]hose skilled in the art understand readily that different antibodies
will have different antibody combining sites, and that the location of the
antibody combining site of an antibody can be determined by routine
experimentation” (App. Br. 6).
We are not persuaded. Appellants’ argument reduces the invention to
the solely functional elements. As Ariad points out, the “written description
requirement also ensures that when a patent claims a genus by its function or
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result, the specification recites sufficient materials to accomplish that
function—a problem that is particularly acute in the biological arts.” Ariad,
598 F.3d at 1352-3. That is the central issue here, where only a single
species of antibody and peptide are disclosed, we conclude that Appellants’
claims “merely recite a description of the problem to be solved while
claiming all solutions to it and . . . cover any compound later actually
invented and determined to fall within the claim’s functional boundaries—
leaving it to the pharmaceutical industry to complete an unfinished
invention.” Ariad, 598 F.3d at 1353.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
disclosure of the Specification failed to demonstrate possession and
descriptive support for Claim 1.
C. 35 U.S.C. § 112, first paragraph, enablement
The Examiner finds that:
the state of the art recognized that it would be highly
unpredictable that linkage of just any peptide to a
therapeutic antibody specific for a therapeutic target or even
the linkage of a particular peptide with just any therapeutic
antibody would provide the requisite antibody-antigen
association having the appropriate affinity wherein upon
administration of such modified therapeutic antibody, the
peptide would inhibit by obstructing the binding site of the
therapeutic antibody, thereby “reducing side effects” and
displacement of the peptide from the binding site upon
binding to the therapeutic target produces a therapeutic
effect.

(Ans. 13).
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Appellants contend that “[o]ne skilled in the art would be able, by
routine experimentation, to bind peptides to antibody combining sites of
other antibodies to provide modified antibodies” (App. Br. 7). Appellants
contend that once “one has made a modified antibody, then one can test the
modified antibody by techniques known to those skilled in the art, in order
to determine whether binding to the therapeutic target has been reduced”
(App. Br. 7). Appellants contend that once the skilled artisan “has tested
and determined that binding of the modified antibody to the therapeutic
target has been reduced, one skilled in the art then would know that such
modified antibody can be used to provide a therapeutic effect while
providing a reduced antibody response against the modified antibody” (App.
Br. 7).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the claims fail to comply with the
enablement requirement?
Findings of Fact
Breadth of Claims
6. Claim 1 is drawn to any therapeutic antibody modified with a
peptide which reduces binding of the antibody to its target.
Presence of Working Examples
7. The Specification teaches a single working example (see FF 5).
Amount of Direction or Guidance Presented
8. The Specification teaches that:
the native antigen, domains thereof, and peptide fragments or
mimotopes are used to modify the ACS. The latter may be
generated from peptide libraries either synthetically or
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biologically-derived. Non-covalently binding chemicals can be
screened from natural or synthetic libraries or from other
available products, for their ability to inhibit antibody binding
to its antigen or a surrogate equivalent.

(Spec. 7, ll. 1-6).
State of the Prior Art and Unpredictability of the Art
9. Li2 teaches that “omission of a single amino 'acid residue at
position 14 or 20 abolishes immunoreactivity yet gives retention of opiate
potency” (Li2 3211, col. 1).
10. Lederman3 teaches that “the arginine→tryptophan substitution
at amino acid 240 ablates the binding of the mAb OKT4 (Lederman,
abstract).
Quantity of Experimentation
11. The Examiner makes no finding regarding the quantity of
experimentation.
Skill in the Art
12. The Examiner makes no finding regarding the skill level in the
art.

2 Li et al, -Endorphin omission analogs: Dissociation of
immunoreactivity from other biological activities, 77 PROC. NAT’L
ACAD. SCI. USA 3211-3214 (1980).
3 Lederman et al., A single amino acid substitution in a common
African allele of the CD4 molecule ablates binding of the
monoclonal antibody, OKT4, 28 MOL. IMMUNOLOGY 1171-1181
(1991).
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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 not drawn to the absence of any teachings
of therapeutic antibodies in the art, but rather to the identification of peptides
which inhibit binding of therapeutic antibodies to their therapeutic target
(see Ans. 12). While, as discussed above, we agree with the Examiner that
there is no description of either the therapeutic antibodies or the peptides or
other binding molecules in the Specification, we are not persuaded by the
enablement rejection.
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The Li and Lederman references simply demonstrate that antibody
binding is exquisitely specific (FF 9-10). They do not demonstrate any
unpredictability in identifying peptides or other compounds which would
reduce the affinity of an antibody to its therapeutic target.
We view this case as similar to Wands itself, where the Court found
that even though a large amount of screening would have been necessary, “a
considerable amount of experimentation is permissible, if it is merely
routine.” Wands, 858 F.2d 737. The Examiner has not provided any
evidence that it would have been anything other than routine to screen a
particular antibody with a library of peptides or other compounds to identify
those which reduced binding of the antibody to its target. The claims do not
require any specific level of reduction of binding, so any level that was not
de minimis would satisfy the claim requirements.
In the absence of any evidence of unpredictability in performing the
screening assay, we are constrained to conclude that undue experimentation
would not have been required to make the claimed invention.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the claims fail to comply with the enablement requirement.
.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C. §
102(b) as anticipated by Hale. Pursuant to 37 C.F.R. § 41.37(c)(1)(2006),
we also affirm the rejections of claims 6, 9, 10, and 17 as these claims were
not argued separately.
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We affirm the rejection of claims 1, 6-10, 12-15, and 17 under 35
U.S.C. § 112, first paragraph as failing to satisfy the written description
requirement.
We reverse the rejection of claims 1, 6-10, 12-15, and 17 under 35
U.S.C. § 112, first paragraph as not enabling for all therapeutic antibodies
modified by any peptide wherein the therapeutic antibody has reduced side
effects and produces a therapeutic effect.

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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